Prevention of Late Depression

Aging Medicine
Series Editors: Robert J. Pignolo Mary Ann Forciea Jerry C. Johnson
OliviaI.Okereke Editor
Prevention
of Late-Life
Depression
Current Clinical Challenges and
Priorities
AGING MEDICINE
Robert J. Pignolo, MD, PhD; Mary Ann Forciea, MD;
Jerry C. Johnson, MD, Series Editors
More information about this series at http://www.springer.com/series/7622

Olivia I. Okereke
Editor
Prevention of Late-Life
Depression
Current Clinical Challenges
and Priorities
Editor
Olivia I. Okereke
Department of Psychiatry
Brigham and Womens Hospital
and Harvard Medical School
Boston, MA, USA
Aging Medicine
ISBN 978-3-319-16044-3 ISBN 978-3-319-16045-0 (eBook)
DOI 10.1007/978-3-319-16045-0
Library of Congress Control Number: 2015935617
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Preface
Prevention of depression in late life is one of todays major health priorities. Late-life
depression is a common and highly disabling condition and is also associated with
higher health care utilization and overall costs. The presence of depression may
complicate the course and treatment of comorbid major medical conditions that are
also highly prevalent among older adultsincluding diabetes, hypertension, and
heart disease. Furthermore, a considerable body of evidence has demonstrated that,
for older persons, residual symptoms and functional impairment due to depression
are commoneven when appropriate depression therapies are being used. Finally,
the worldwide phenomenon of a rapidly expanding older adult population means
that unprecedented numbers of seniorsand the providers who care for themwill
be facing the challenge of late-life depression.
For these reasons, effective prevention of late-life depression will be a critical
strategy to lower overall burden and cost from this disorder. Indeed, world leaders
in the field of depression have called for a renewed focus on prevention. This textbook
will illustrate the imperative for preventing late-life depression, introduce a broad
range of approaches and key elements involved in achieving effective prevention,
and provide detailed examples of applications of late-life depression prevention
strategiesall with consideration of medical and scientific, economic, policy, cultural,
and global health perspectives.
Boston, MA, USA Olivia I. Okereke, M.D., M.S.
v
Contents
1 Prevention of Major Depression: A Global Priority ............................ 1

Charles F. Reynolds III
2 The Framework for Prevention ............................................................. 5
Robert A. Schoevers and Elisabeth Duursma
3 Social and Behavioral Risk Factors for Late-Life Depression ............ 19
Ankura Singh and Olivia I. Okereke
4 Prevention of Depression in Medical Conditions ................................. 33
Liming Dong and Joseph J. Gallo
5 Vascular Depression and the Role of Neuroimaging
and Biomarkers ....................................................................................... 57
Sara L. Weisenbach, Nicolette M. Gabel, and Emily M. Briceo
6 Measurement and Assessment in Late-Life Depression ...................... 83
Olivia I. Okereke
7 Indicated Prevention ............................................................................... 99
Pim Cuijpers, Claudia Buntrock, David Daniel Ebert,
Aartjan T.F. Beekman, and Charles F. Reynolds III
8 Selective and Universal Prevention of Late-Life Depression .............. 113
Olivia I. Okereke
9 Health Policy and Economic Aspects of Late-Life
Depression Prevention ............................................................................ 135
10 Depression Among Blacks During Late Life:
Examining Within-Group Variations .................................................... 153
Shanna Brewton-Tiayon, Daphne C. Watkins, Niki Matusko,
and James S. Jackson
vii
viii Contents
11 Global Priorities and Possibilities.......................................................... 171

Steven M. Albert, Offer E. Edelstein, Stewart J. Anderson,
Mary Amanda Dew, and Charles F. Reynolds III
Index ................................................................................................................. 185

Contributors
Steven M. Albert Department of Behavioral and Community Health Sciences,

Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
Stewart J. Anderson Department of Behavioral and Community Health Sciences,
Aartjan T.F. Beekman, M.D., Ph.D. Department of Psychiatry, EMGO Institute
for Health and Care Research, VU University, Amsterdam, The Netherlands
Shanna Brewton-Tiayon, M.A. Department of Sociology, University of Maryland,
College Park, MD, USA
Emily M. Briceo, Ph.D. Department of Psychiatry, University of Michigan
Medical School, Ann Arbor, MI, USA
Claudia Buntrock, M.Sc. Division Health Trainings online, Leuphana University
Innovation Incubator, Lueneburg, Germany
Pim Cuijpers, Ph.D. Department of Clinical Psychology, EMGO Institute
for Health and Care Research, VU University, Amsterdam, The Netherlands
Division Health Trainings online, Leuphana University Innovation Incubator,
Lueneburg, Germany
Mary Amanda Dew Department of Behavioral and Community Health Sciences,
Liming Dong Department of Mental Health, Bloomberg School of Public Health,
Johns Hopkins University, Baltimore, MD, USA
ix
x Contributors
Elisabeth Duursma Department of Education, University of Wollongong,

Wollongong, NSW, Australia
David Daniel Ebert, Ph.D. Department of Psychology, Clinical Psychology
and Psychotherapy, Philipps University, Marburg, Germany
Division Health Trainings online, Leuphana University Innovation Incubator,
Lueneburg, Germany
Offer E. Edelstein Department of Behavioral and Community Health Sciences,
Nicolette M. Gabel, Ph.D. Department of Physical Medicine and Rehabilitation,
University of Michigan Medical School, Ann Arbor, MI, USA
Joseph J. Gallo M.D., M.P.H. Department of Mental Health, Bloomberg School
of Public Health, Johns Hopkins University, Baltimore, MD, USA
James S. Jackson, Ph.D. Institute for Social Research, University of Michigan,
Ann Arbor, MI, USA
Niki Matusko, M.A. Institute for Social Research, University of Michigan, Ann
Arbor, MI, USA
Olivia I. Okereke, M.D., M.S. Department of Psychiatry, Brigham and Womens
Hospital and Harvard Medical School, Boston, MA, USA
Charles F. Reynolds III, M.D. Department of Clinical Psychology, EMGO
Institute for Health and Care Research, VU University, Amsterdam, The Netherlands
Department of Psychiatry, EMGO Institute for Health and Care Research, VU
University, Amsterdam, The Netherlands
Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh,
PA, USA
Department of Behavioral and Community Health Sciences, Graduate School of
Public Health, Pittsburgh, PA, USA
Robert A. Schoevers Department of Psychiatry, University Medical Center
Groningen, Groningen, The Netherlands
Ankura Singh, M.P.H. Channing Division of Network Medicine, Brigham and
Womens Hospital, Boston, MA, USA
Daphne C. Watkins, Ph.D. School of Social Work, University of Michigan, Ann
Arbor, MI, USA
Sara L. Weisenbach, Ph.D. Department of Psychiatry, University of Illinois at
Chicago, Chicago, IL, USA
Research and Development, Jesse Brown VA Medical Center, Chicago, IL, USA
Prevention of Major Depression:
A Global Priority 1
Charles F. Reynolds III
Abstract
Prevention of depression and its associated common mental disorders is a priority
across the life cycle, and particularly in older adults. Currently available data from
randomized clinical trials show that the rate of these disorders can be reduced on
average 2025 % over 12 years of follow-up. This is important with respect to:
(1) reducing the current burden of suffering, even in the context of subsyndromal
symptoms and (2) protection from fully syndromal depression and its down-
stream consequences, including poor adherence with co-prescribed medical and
behavioral interventions (because depression undermines adherence), family
caregiving burden (because depression imposes considerable burden on family
as well as patients), suicide (because depression is a major risk factor for suicide
in older patients), and dementia (because depression is an important and poten-
tially modifiable risk factor for both vascular and Alzheimers dementia).
Additional work is needed to clarify biological and psychosocial mediators and
moderators of depression prevention intervention; and to build scalable models of
depression prevention for low-resource countries.
Keywords
Depression Indicated prevention Older adults
C.F. Reynolds III, M.D. (*)

Department of Clinical Psychology, EMGO Institute for Health and Care Research,
VU University, Van der Boechorststraat 1, Amsterdam 1081 BT, The Netherlands
Department of Psychiatry, EMGO Institute for Health and Care Research, VU University,
Amsterdam, The Netherlands
Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
Department of Behavioral and Community Health Sciences, Graduate School of Public
Health, Pittsburgh, PA, USA
e-mail: ReynoldsCF@upmc.edu
Springer Science+Business Media New York 2015 1

O.I. Okereke (ed.), Prevention of Late-Life Depression,
Aging Medicine 9, DOI 10.1007/978-3-319-16045-0_1
2 C.F. Reynolds III
Prevention of common mental disorders, particularly major depression, represents

one of the grand challenges in global mental health (grandchallengesinglobalMH@
NIH.org). Meta-analyses of more than 30 randomized trials conducted in the High
Income Countries show that the incidence of new depressive and anxiety disorders
can be reduced by 2550 % over 12 years, compared to usual care, through the use
of learning-based psychotherapies (such as interpersonal psychotherapy, cognitive
behavioral therapy, and problem solving therapy) [1, 2]. In addition, a recent study,
the MANAS trial (project to promote mental health in the Konkani language),
conducted in Goa, India, demonstrated that the use of lay health counselors, as part
of a collaborative stepped-care intervention, not only increased recovery rates from
common mental disorders (anxiety and depression) in a mixed aged sample of
patients attending public primary care facilities [3] but also reduced the incidence of
common mental disorders in those presenting initially with subsyndromal symp-
toms of depression and anxiety. The MANAS trial was particularly important from
the perspective of workforce issues. That is, given the shortage of mental health
specialists in Low and Middle Income Countries (LMICs), MANAS demonstrated
the advantage of task shifting, that is, the rational redistribution of tasks among
health workforce teams in order to make more efficient use of lay and professional
human resources.
Why is the prevention of major depression important, from a global health
perspective? [4]. The case for depression prevention is compelling and represents
the key rationale for this volume: (1) Major depression is both prevalent and dis-
abling, typically running a relapsing or chronic course. Social factors, particularly
related to economic or social disadvantages (low education and violence), are major
determinants. (2) Major depression is often comorbid with other chronic conditions
like diabetes, amplifying the disability associated with these conditions and worsen-
ing family caregiver burden. (3) Depression is associated with worse physical health
outcomes, partly mediated through poor treatment adherence, and it is associated
with excess mortality after myocardial infarction, stroke, and cancer. It is also the
major risk factor for suicide across the life span and particularly in old age.
(4) Available treatments are only partially effective in reducing symptom burden,
sustaining remission, and averting years lived with disability. (5) The treatment gap
for people with mental disorders has been extensively documented, especially in
LMICs, where up to 90 % of people with mental disorders do not receive effective
treatments. Finally, (6) the great scarcity of mental health specialists in most coun-
tries and the inequity of the distribution of these specialists is a major barrier to
closing the treatment gap. The existence of the treatment gap and the attendant
workforce issues underscore the need for developing effective models of prevention
that can be implemented by health workers with shorter training and fewer qualifi-
cations, in order to make more efficient use of the available human resources for
health. Thus, the development of depression prevention strategies, especially in
LMICs, would be a method of addressing multiple inequalities (e.g., treatment gaps,
workforce barriers) in global mental health.
Promising approaches circa 2013 focus on persons who experience risk factors
for depression, particularly functional limitations as a result of illnesses such as
1 Prevention of Major Depression: A Global Priority 3
stroke or macular degeneration; small social networks; or who are already living with
subsyndromal symptoms. Epidemiological modeling has suggested that preventive
interventions would have the highest impact and lowest effort in the presence of
subsyndromal depressive symptomsindicated prevention in the Institute of
Medicines lexiconwith numbers needed to treat to prevent one case of 3 or 4.
In addition the financial costs of averting 1 year lived with depression-related dis-
ability is below the current ceiling of $30,000$50,000 generally accepted by health
policy makers as cost effective.
What are the best studies candidate interventions circa 2013? Brief learning-based
approaches, already shown to have efficacy in the treatment of depressive disorders,
pain, or insomnia disorders, offer promise to reduce risk and to positively alter trajec-
tories of illness. While antidepressant medications are the most widely used modality
for treating prevalent cases of major depression, their use in subthreshold depression
is not yet strongly supported and may be ill-advised due to a lack of evidence of
efficacy in mild depression, as well as adverse effects in older adults such as hypona-
tremia, risk for falls, bone demineralization, and cataracts. Psychological interven-
tions may be desirable for reasons of safety and patient preference. Problem solving
therapy (PST), in which behavioral activation is an important component, has been
used in depression prevention studies successfully, is more easily utilized than IPT or
CBT, and can be embedded within a clear service model. Teaching coping skills may
enhance resilience to stress and diminish the sense of loss of control (feeling trapped
or helpless) at the core of depression. Similarly, to offer another example of a possi-
bly effective behavioral intervention, teaching strategies for better sleep (because
poor sleep is a known and established risk factor for depression) may diminish affec-
tive reactivity and enhance cognitive flexibility. Thus, there may be a synergy
between PST-based approaches and those that enhance sleep quality. In this context,
Brief Behavioral Treatment for Insomnia (BBTI) seems particularly promising, since
it has been shown to improve sleep quality and to reduce symptoms of depression
and anxiety [5].
In terms of scalability, interventions such as PST are also practicable: safe, cheap,
deliverable by general medical clinicians (including nurses, social workers, and
potentially lay health counselors), and more likely to be acceptable to patients than
antidepressant medication before major depression is even diagnosable.
Even with preexisting symptoms of depression, only some are at risk for pro-
gressing to a major depressive episode, and only some will benefit from preventive
interventions. Developing a deeper understanding of the risk architecture for
depression is one of the major challenges facing the field. Targeted prevention will
likely require a combination of biological assessments (e.g., genetics, neuroimag-
ing, cytokine levels). Blood-based measures are the most likely to be feasible in
community and office settings. As an illustration of the need for biosignatures
research to guide and inform the rational introduction of depression prevention
strategies with true public health relevance, we cite current efforts at the NIMH-
sponsored Center for Depression Prevention at the University of Pittsburgh to
study synergistic interactions among the serotonin system, the hypothalamic pitu-
itary adrenal axis, systemic inflammation, growth factors such as brain-derived
4 C.F. Reynolds III
neurotrophic factor, psychosocial stressors, and vascular comorbidity. We note in

this context that there may be a role for omega-3 fatty acids in moderating depres-
sion vulnerability. In addition, mRNA transcriptome patterns are also associated
with depression and age, affording a linked and novel approach for developing
transcript biosignatures of changing depression risk over time. While depression is
not likely to be the result of a single set of vulnerabilities, if the field can identify
a set of various subtypes of vulnerability, they may enhance the opportunity for
effective, targeted prevention.
The full implementation of evidence-based depression prevention strategies has
yet to take place. In order to close the gap between what we know and how to get
it done, the Global Consortium for Depression Prevention (www.preventionofde-
pression.org) was formed in 2011 as a result of meetings in Pittsburgh and Utrecht.
The Consortium has published a position paper in JAMA [1] and has advocated for
strengthening of research and dissemination efforts. These priorities address ways
of improving access to effective strategies by those at risk and advocate the devel-
opment of Internet based strategies to reach underserved populations of at-risk
persons.
In summary, the current volume edited by Olivia Okereke and colleagues repre-
sents a state of the art presentation of the public health need for depression prevention,
promising evidence-based strategies, the need for biosignatures research to elucidate
at a deep level the risk architecture of depression, and global workforce issues that
impinge upon the ultimately scalability of depression prevention models.
Supported in part by P30 MH90333 and by the University of Pittsburgh Medical Center Endowment
in Geriatric Psychiatry
References
1. Cuijpers P, Beekman ATF, Reynolds CF. Preventing Depression: A Global Priority. JAMA.
2012;307(10):10331034.
2. van't Veer-Tazelaar PJ, van Marwijk HW, van Oppen P, van Hout HP, van der Horst HE, Cuijpers
P, et al. Stepped-care prevention of anxiety and depression in late life: a randomized controlled
trial. Arch Gen Psychiatry. 2009;66(3):297304.
3. Patel V, Weiss HA, Chowdhary N, Niak S, Pednekar S, Chatterjee S, et al. Effectiveness of an
intervention led by lay health counsellors for depressive and anxiety disorders in primary care
in Goa, India (MANAS): a cluster randomised controlled trial. Lancet. 2010;376:208695.
4. Reynolds CF, Cuijpers P, Patel V, et al. Early Intervention to Reduce the Global Health and
Economic Burden of Major Depression in Older Adults. Annual Review of Public Health
2012;33:123135.
5. Buysse DJ, Germain A, Moul DE, Franzen PL, Brar LK, Fletcher ME, et al. Efficacy of brief
behavioral treatment for chronic insomnia in older adults. Arch Intern Med. 2011;171(10):
88795.
The Framework for Prevention
2
Robert A. Schoevers and Elisabeth Duursma
Abstract
Depression is a disease affecting millions of people worldwide, has a high risk of
recurrence and carries high health care and other societal costs. Prevention of
depression is essential, in particular since depression is more likely to persist
when no intervention is provided. In this chapter we discuss the prevention
framework developed by the Institute of Medicine (IOM) for providing a model
to understand the different objectives of interventions. We also discuss risk fac-
tors specific for the elderly and identification of the population at risk. Finally we
review some best practices in depression interventions and offer some sugges-
tions for future research.
Keywords
Depression prevention Prevention framework Risk factors
2.1 Introduction: Prevention in Psychiatry
Depression is a common disorder: more than 350 million people around the globe
suffer from depression [1]. The World Mental Health Survey found that on average
1 in 20 people reported having an episode of depression in the last year [2]. Women
are more likely to suffer from depression than men [3]. However, many people
R.A. Schoevers (*)

Department of Psychiatry, University Medical Center Groningen,
Postbus 30001, Hanzeplein 1, 9700 RB Groningen, Netherlands
e-mail: r.a.schoevers@umcg.nl
E. Duursma
Department of Education, University of Wollongong, Wollongong, NSW, Australia

6 R.A. Schoevers and E. Duursma
suffering from depression do not receive any care and approximately a third of those
receiving care do not respond to current treatments. The risk of recurrence is high,
also in older persons: half of those who have experienced a major depression will
experience one or even more recurrences [4]. The disease burden of depression is
substantial due to high health care costs but also to lost production days [5, 6].
Depression increases the risk at death: among people suffering from depression the
risk of dying is 1.65 times higher than among people without a depression [7], with
a dose-response relation between severity and duration of depression and the result-
ing excess mortality [8]. In adults, the average length of a depressive episode is
8 months but among 20 % of people the depression lasts longer than 2 years [9].
Depression is projected to be among the top three leading causes of disease burden
in 2030. The changing population in many Western countries will only shift this
burden even further to the aging population. Late-life depression is also associated
with substantially increased health care use [10, 11] and economic costs [12, 13].
Although progress has been made in the area of treatment of depression in the
last decades, it has had a limited impact on the public health effects of mental health
problems. It has been estimated that in Australia, for example, 60 % of people with
an affective disorder receive treatment, and using guidelines and standards only
34 % receives effective treatment [14]. This translates in preventing 15 % of Years
Lived with Disability [15], a measure of disease burden [14] and stresses the need
for prevention [16].
Primary health care providers frequently do not recognize depression, in particu-
lar among elderly. Older people may present their depressive symptoms differently
from younger adults, with more emphasis on physical complaints [17, 18]. Adequate
diagnosis of late-life depression can also be hampered by comorbid conditions such
as Parkinson and dementia that may have similar symptoms, or by the fact that
elderly people as well as care workers may assume that feeling down is part of
becoming older [17, 18].
Until recently, there was only little attention for scientifically based systematic
prevention of major depression [19]. This is in contrast to other areas of medicine
where prevention has been around for some time, for example, in vaccinations to
prevent infectious diseases [20]. In psychiatry, prevention programs do exist for
specific risk groups, such as support groups for children whose parents have psychi-
atric disorder or relapse prevention for certain patient groups. Nevertheless, until
recently there was no targeted, systematic, and evidence-based prevention of com-
mon mental illnesses such as depression.
The demographic shift in Western countries is expected to lead to an increased
health burden in regard to late-life depression. Effective treatments are available for
depression; however, budgetary constraints and a lack of qualified therapists, even
in high-income countries, aggravate the problem [21]. Many people suffering from
depression do not seek professional help or are not identied as depressed [21].
Almost 14 % of elderly people living in community-type living suffer from a severe
depression requiring clinical attention [22] and more than 50 % of those have a chronic
course [4, 23]. Smit et al. reported an incidence of 6.1 % of chronic or recurrent
depression among a sample of 2,200 elderly people (ages 5585) [21].
2 The Framework for Prevention 7
It has been estimated that interventions can reduce the incidence of depression
by 20 % [2426]. This number is promising; however, spontaneous remission
occurs even in later life in approximately 23 % of new cases [4, 9, 27] and interven-
tions should ideally be targeted at the other 77 % where depression would be more
likely to persist when there is no intervention [28].
In this chapter we will discuss how the population at risk can be best targeted
using a basic theoretical framework. We will first discuss the different types of pre-
vention. Next, we will focus on the risk profile and the evidence-based possibilities
for different types of prevention among the general population. Finally, we will
illustrate how the framework can be utilized in a few examples.
2.2 Types of Prevention
Prevention differs from intervention and treatment as it is aimed at general popula-

tion groups who vary in risk level for mental health problems such as late-life
depression. The Institute of Medicine (IOM) has introduced a prevention frame-
work, which provides a useful model for comprehending the different objectives of
the interventions [29]. The overall goal of prevention programs is reducing risk
factors and enhancing protective factors.
The IOM framework distinguishes three types of prevention interventions:
(1) universal preventive interventions, (2) selective preventive interventions, and
(3) indicated preventive interventions. Universal preventive interventions are tar-
geted at the general audience, regardless of their risk status or the presence of symp-
toms. Selective preventive interventions serve those sub-populations who have a
significantly higher than average risk of a disorder, either imminently or over a
lifetime. Indicated preventive interventions target identified individuals with mini-
mal but detectable signs or symptoms suggesting a disorder. This type of prevention
consists of early recognition and early intervention of the diseases to prevent dete-
rioration [30]. For each of the three types of interventions, the goal is to reduce the
number of new cases. The goal of treatment, on the other hand, is to reduce preva-
lence or the total number of cases. By reducing incidence you also reduce preva-
lence [5].
The IOM Framework offers a theoretical foundation for advancing how we think
about the spectrum of prevention activities [30]. The framework allows for fitting
the needs of the participants with the design and implementation of the intervention.
Different aspects are associated with the IOM Framework: (1) defining populations,
(2) recruiting prevention participants and providing access to interventions, (3)
designing and selecting appropriate interventions, and (4) identifying appropriate
outcomes [30].
The IOM Framework identifies different categories of populations depending on
their risk of developing (late-life) depression. This is one of the most important
steps in guiding prevention planning and implementation in order to realize the full
potential of the framework [30]. First of all different categories of populations that
are broadly defined by their risk of late-life depression are identified. It is important
to distinguish between universal, selective, and indicated populations. Once the cri-
teria for the population are identified it is important to gain access to the participants
in order to recruit the appropriate participants. Appropriate interventions need to be
designed and selected. Finally, the specific outcomes need to be defined, which is
one of the most complex aspects of prevention research.
As mentioned, prevention research differs from treatment research in various
ways. One of the most important differences is the fact that participants in treatment
studies already meet the criteria for the illness being studied, such as depression.
The intervention is targeted at improvement or remission of the specific condition
quicker than if no intervention had taken place. In prevention research, the partici-
pants do not meet the specific criteria for the illness being studied and the overall
goal of the intervention is to prevent the development of a clinical illness at a lower
rate than a comparison group [5].
2.3 Risk Factors
Depression occurs more frequently among people with a familial, possibly genetically
determined, vulnerability and its heritability is estimated to be between 30 and 40 %
[31, 32]. Having a personal history of depression or having a family history of depres-
sion can increase the risk for depression [33]. However, environmental and psycho-
logical factors also play a substantial role in its onset. Environmental factors that
increase the chances of developing a major depression include the loss of a loved one
or developing a physical illness. Support from the environment such as family or
friends can also influence whether people develop a depression or not, in particular in
the case of a major life event [33]. Psychological factors include specific personality
traits that influence how people cope with adversity. Persons with a stronger sense of
mastery (believing one can cope with, and also influence things that are happening to
them) have a lower chance of becoming depressed than persons who feel they have
less control [34]. Early negative life events, such as personal loss, also play a signifi-
cant role in the development of depression. These earlier experiences increase the risk
of developing a depression also at a later age [35].
Table 2.1 shows the stress vulnerability model that can be used to map the origin
of depression. Stressors such as loss, diseases, as well as vulnerability factors such as
familial disposition or lack of social network play a role in this model. Risk factors
can be divided into personal and environmental factors.
Depression can be viewed as the result of an interaction between different factors.
A couple of risk factors occur more frequently among the elderly than among young
adults. The loss of a loved one or the loss of a social role (e.g., employment),
decrease of social support and network, and the increasing change of isolation occur
more frequently among the elderly. Many elderly also suffer from physical diseases:
64 % of elderly aged 6574 has a chronic disease [36] and the risk of cognitive
deterioration expands rapidly after age 65. It is important to note that depression
often co-occurs with other disorders such as physical illness and other mental health
Table 2.1 Risk factors depression among elderly

Stressor Vulnerability
Personal Physical illness Sex (female)
Functional limitations Genetic/familial
Cognitive degeneration History of depression
Personality
Coping mechanism
Education/intelligence
Environment Loss (of partner) Social network/support
Isolation Socio-economic status
Other life-related problems
problems (comorbidity). Losing a spouse can have significant mental health effects.
Almost half of all widows and widowers during the first year after the loss meet the
criteria for depression according to the DSM-IV [37]. Depression after loss of a
loved one is normal in times of mourning. However, when depressive symptoms
persist during a longer period of time it is possible that a depression is developing.
Zisook and Shuchter found that a year after the loss of a spouse 16 % of widows and
widowers met the criteria of a depression compared to 4 % of those who did not lose
their spouse [38]. Widows and widowers are a risk group for depression [39].
People with a chronic physical disease are also at a higher risk of developing a
depression. An estimated 1236 % of those with a chronic physical illness also
suffer from clinical depression [40]. For example, around 25 % of cancer patients
suffer from depression [40]. For other neurological illnesses such as multiple scle-
rosis and epilepsy it is assumed the total number of depression cases is even
higher [39].
Depression is relatively common among elderly residing in hospitals and retire-
ment- and nursing homes. An estimated 611 % of residents have a depressive illness
and among 30 % have depressive symptoms [41]. This could be caused by, among
other things, loss of autonomy and social support, presence of chronic diseases,
awareness of own mortality, or demands made by the institution [39].
Loneliness is common among the elderly. Among those of 60 years or older,
43 % reported being lonely in a study conducted by Perissinotto et al. [42]. Long-
term loneliness can affect health and quality of life among many elderly. Loneliness
is often associated with physical and mental complaints; apart from depression it
also increases the chance of developing dementia and excess mortality [43].
2.4 Identification of the Population At-Risk
When initiating and testing the effectiveness of indicated prevention, it is essential

to first select a group of people who could benefit from the intervention. Furthermore,
we need to select a risk profile. Third, there needs to be an intervention that addresses
these risk factors in an effective and cost-effective way. This can be reached by
answering the following three questions:
1. What are the chances of developing a depression in a person with a certain
risk-profile?
The strength of the association between risk factors and the onset of depression
is often expressed as an odds ratio signifying the difference in probability to develop
the disorder between those with and those without a certain risk factor (or combina-
tion of factors). However, for an individual, the only number that really counts is the
absolute risk that he or she will actually develop a depression within a certain time
period (e.g., expressed in a percentage). Pragmatic (cost-benefits) as well as ethical
reasons also require that indicated prevention studies target those who are at sub-
stantial risk of developing the disease. Those are the people that may benefit most
from a preventive intervention, and their baseline risk to get the disorder makes it
worthwhile. The downside is that people who do not view themselves as ill are
made aware of the risk that they could develop a disorder. They are then encouraged
to change their behavior or lifestyle or to follow an indicated prevention program
for a disease that they possibly will never develop. The costs of this, expressed in the
strain and concern for the individual, but also financially, have to be weighted
against the benefits [19].
2. What proportion of incident depressions can be attributed to specific factors?
From the public health perspective it is important to know what the potential
health benefits would be if the harmful effect of certain risk factors could be removed.
What health benefits would arise from this, at which efforts and costs? To measure
this the population attributive fraction (PAF) can be used. The PAF is expressed in a
percentage and demonstrates the decrease of the percentage of incidences (number
of new cases) when the harmful effects of the targeted risk factors are fully taken
away. For public health it would be more effective to design an intervention targeted
at a risk factor with a high PAF than a low PAF. When a risk factor with a high PAF
can be treated, or if people would be allowed to adequately deal with the negative
effects of the risk factor, this would provide a meaningful public health gain [44]. An
example of a study examining these associations is Smit et al., which shows that
persons are at a high risk of depression when they experience symptoms of anxiety,
functional impairments, two or more chronic illnesses, and either a low attained edu-
cational level or below average levels of mastery, while living without a partner [21]
These risk factors are responsible for 48.7 % of the incidence of depression, indicat-
ing that large health gains can be generated if the effects of these risk factors could
be contained. Interestingly, no more than 8.3 % of the older population has these
characteristics, suggesting that this can be done efficiently.
3. How many people need to undergo preventative intervention to prevent one new
case of depression?
An intervention needs to be effective in order to be implemented; this means that
it has to show a statistically significant difference with placebo or other treatment.
Secondly, it needs to be effective; it needs to prove its benefits also in real life
(everyday care) circumstances. Thirdly, it needs to be efficient. The measure to
address this is the Number Needed to Be Treated (NNT). The NNT expresses how
many people need to be treated to prevent the onset of one new case with the disorder;
the lower the number, the more efficient the intervention [45].
To summarize, an indicated preventative intervention would ideally be targeted
at a relatively small group of people with a high, absolute chance of developing the
disease, and a risk profile that is responsible for a high PAF. Furthermore, there
needs to be an intervention that is both effective and efficient.
A practical example of this approach is provided in a paper by Schoevers et al.
[44]. In a large sample of community living elderly people, two models for selective
(people at elevated risk) and indicated (those with subsyndromal depressive symp-
toms) prevention were compared. The goal was to identify groups in primary care
with a high vulnerability for depression using easily identifiable criteria (e.g., gen-
der, education, disability, widowed) that can be used in primary care as a screener to
identify patients at elevated risk of developing a depression. The results showed that
indicated prevention, which includes identifying subsyndromal depressive symp-
toms as the primary risk indicator, was the best way to identify groups who were at
a high risk of developing depression [44]. People who had depressive symptoms
had a risk of almost 30 % and accounted for 24.6 % of new cases at follow-up.
In terms of selective prevention, the study demonstrated that elderly people who
were recently widowed were at great risk of developing depression, and having a
chronic medical condition increased this risk. The Schoevers et al. study showed
that indicated prevention is the preferred option when detecting large groups of
subjects at high risk of developing depression. However, compared to selected pre-
vention, indicated prevention does require extra effort in screening for subsyndro-
mal depression [44] (Figs. 2.1 and 2.2).
It is also of interest to note the relation between absolute risk, PAF, and
NNT. Figure 2.3 shows graphically how a more detailed and specific description of
the target group results in a higher absolute risk, a lower NNT, and also a lower
PAF. This is helpful in determining the costs and benefits of interventions aiming at
more specific or broader subgroups in the population.
2.5 What Interventions Work Best?
Over time, universal and selected intervention services could be the most effective
ways of reducing the incidence of the disease in the population. Unfortunately very
large samples are required to demonstrate reductions in universal or selected inter-
ventions [46]. The incidence of major depression in the general population is around
1.7 % per year [47]. If a preventive intervention would be able to reduce the inci-
dence by 22 % compared to the control group (to 1.3 %), as was found in a meta-
analysis of preventive interventions [28], both experimental and control group
would need at least 17,253 participants. However, if the preventive intervention
would be made twice as effective (so reducing the incidence by 44 %), you would
Fig. 2.1 Selective prevention model
Fig. 2.2 Indicated prevention model. ARabsolute risk, NNTnumbers needed to be treated, and
AFattributable fraction
60
50
40
AR
30 NNT
AF
20
10
0
depressed disable alone female
Fig. 2.3 Consequences of adding risk factors to the prediction model in terms of absolute risk
(AF, in %), numbers needed to be treated (NNT, in %), and attributable fraction (AF, in %)
only need 3,933 participants per condition, which is still an impressive number [5].
If the incidence rate is higher in the target population, which is usually the case in
selective and even more so in indicated prevention, the number of participants
needed to prove an effect is much smaller [5]. This shows that, even though univer-
sal interventions may be effective, its effect is harder to prove than that of indicated
prevention. Hundreds of studies have been conducted examining the effectiveness
of prevention programs targeted at mental health [46]. Meta-analyses have demon-
strated that prevention of psychiatric illnesses among adults is possible. Perhaps in
line with the above, the strongest effects of prevention were observed with depres-
sive illnesses and indicated preventive prevention [16, 46].
It is also important to examine the specific risk factors and their association with
depression onset. Several risk factors such as gender, socioeconomic status, trauma,
and family history are known to contribute to major depression [5]. These so-called
lifetime risk factors are useful in identifying groups for selected interventions but
not for identifying participants for indicated prevention trials since the specificity of
those well-known risk factors is low for predicting short-term risks [5]. Muoz et al.
also stress the importance of distinguishing between risk factors that can be modi-
fied and those that function primarily as markers. Family and personal history can-
not be modified while stressful life events can. Having a past history of depressive
episodes is a high-risk marker of new major depressive episodes. Those individuals
who have had a major depressive episode but currently do not meet criteria for a
depression could be at risk for a recurrence or relapse [5]. High levels of depressive
symptoms are known to be short-term predictors of major depression [48]. When
selecting groups at risk for preventive interventions, these aspects need to be taken
into account.
2.6 Critical Remarks
Although prevention programs could reduce the incidence of late-life depression,

there are several problems related to prevention. Compliance is an important factor,
which possibly reduces the effectiveness of an intervention. Patients with depressive
symptoms might have more difficulty in participating in an intervention, even bib-
liotherapy, due to their symptoms. Furthermore, online interventions are on the one
hand easy to access; on the other hand face-to-face contact (possibly as blended care
together with online interventions) increases compliance [49].
Identifying the right population may also be difficult, in particular among elderly
patients who are likely to suffer from other physical illnesses that complicate diag-
nosis and treatment. Older people may believe that depression is part of a specific
stage in life, associated with the loss of a spouse, and be less inclined to seek help
for their depression. It is also important to examine the risk factors for developing a
mental disorder in general, such as social isolation or abuse in childhood.
Furthermore, studying how depression could have a contagious effect on those close
to the patient is also essential [19].
It is important to mention that available research studies on prevention programs
currently have a follow-up no longer than 1 year. At this time there is no evidence
that prevention programs have longer term effects on reducing the disease burden.
It is theoretically possible that these interventions only postpone the development of
the illness. Still, the health gains are then already substantial, and it is likely that if
people at risk cope with depressive complaints successfully, their chances of not
becoming depressed later on are also increased [20].
Another interesting aspect with regard to the potential health gains of depression
prevention is that risk factors among the elderly for preventing anxiety and depres-
sion overlap for a major part. There is some evidence that preventative interventions
can also reduce the onset of anxiety disorders [50], and in older persons depression
is often preceded by anxiety disorder [44]. This makes it likely that the beneficial
health outcomes of depression prevention are larger than those that are currently
modeled in prevention research.
Another important point to be made is the following. In the above examples, it is
assumed that, for example, when calculating NNTs, there is an intervention with
100 % efficacy. Research consistently shows that around 20 % of the incidence of
depression can be reduced by preventive interventions, so NNT values should be
multiplicated by 5 to reach a reliable estimate of the benefits of prevention.
Furthermore, not for all risk factors a preventive intervention is available, even
though effects of interventions may of course generalize to other domains.
Lastly, prevention research introduces an important ethical question. When pre-
ventive measures are implemented, this means that a large number of people have to
be informed that they are at elevated risk to develop a disorder. On the same hand,
the majority of these persons will not develop the disorder. Still, they will be
confronted with a new threat that may affect their quality of life and even behavior,
even if they decide not to participate. This is another reason for the field to develop
risk profiles that are as specific as possible, and select persons with a high risk so
that costs and benefits of the intervention remain in balance.
2.7 Conclusion
Cuijpers et al. have identified several research priorities for the prevention of depres-
sion: It is important to improve access to effective strategies for those at risk [19].
For example, in order to prevent depression among older people who also suffer
from a physical illness, preventive research needs to be incorporated in health care
settings and social services. Preventive interventions often have multiple effects
beyond depression or mental illness in general; it is imperative to measure multiple
outcomes, including economic, educational, and social functioning. Other priorities
include studying how depression in one person has contagion effects on others close
to him/her and focusing on risk factors for developing mental disorder in general
(e.g., social isolation, child abuse) [19].
It is essential to continue developing methods to identify individuals at high risk
for major depression, for example, by focusing on risk factors for developing mental
disorders such as sleep disturbance, child abuse and neglect, social isolation, or dis-
abilities related to medical and neurological diseases [19]. During the at-risk phase
it is still unclear which disorder will possibly develop and collaborations between
different subfields of mental disorders could increase prevention efforts [19]. In this
chapter, we outlined the framework for prevention, discussed the IOMs prevention
framework, and discussed the risk factors for developing depression among the
elderly. Furthermore we discussed how to identify the population at risk and which
interventions work best. Although we have gained tremendous insight in the identi-
fication and treatment of depression among the elderly, future research needs to
develop specific risk profiles to better identify and treat those with depression.
Indicated and selective preventions appear to be the most successful in prevent-
ing depression to date; however, more research needs to be conducted in larger
samples to determine which prevention method is really most effective. Additionally,
it is important to include longer follow-ups in studies on depression prevention to
determine the persistence of the outcome of preventive interventions.
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Social and Behavioral Risk Factors
for Late-Life Depression 3
Abstract
We describe the roles of social, psychological, and behavioral risk factors in the
development of late-life depression. These risk factors are considered within
three major categories: sociodemographic, social/psychological, and lifestyle/
behavioral; specific examples are provided of each. Attention is given to the con-
trast between readily modifiable vs. non-modifiable factors, as well as the
implications for translating knowledge of risk factor-depression associations into
late-life depression prevention strategies. Detailed description is provided on the
current evidence regarding how these factors relate to the risk of incident depres-
sion among older adults, where emphasis is placed on evidence from well-
conducted prospective studies.
Keywords
Demographic Psychological Lifestyle Behaviors Prevention Geriatric
Depressive disorders Cohort studies Epidemiology Risk marker
3.1 Introduction
Social, psychological, and behavioral risk factors have a major role in late-life
depression prevention. First, a growing body of literature has identified numerous
such factors as potential key contributors to risk of late-life depression. Second, as
A. Singh, M.P.H.
Channing Division of Network Medicine, Brigham and Womens Hospital, Boston, MA, USA
O.I. Okereke, M.D., M.S. (*)
Department of Psychiatry, Brigham and Womens Hospital and Harvard Medical School,
181 Longwood Avenue, 3rd floor, Boston, MA 02115, USA
e-mail: ookereke@partners.org

20 A. Singh and O.I. Okereke
Table 3.1 Potential social and behavioral risk factor categories in late-life depression
Category Potential risk factor/risk marker areas
Demographic Age
Gender
Race/ethnicity
Socioeconomic status
Educational attainment
Marital status
Living/residential status (e.g., alone vs. with others)
Social/psychological Social network
Social support
Caregiving burden
Spousal or other major loss
Major adverse life event or stressful event
Perceived stress
Loneliness
Lifestyle/behavioral Physical activity/exercise
Smoking
Alcohol consumption
Overweight/obesity
Diet
Leisure activities
many of these factors are modifiable, it is important to identify the potential benefits
of interventions that may mitigate their impact. Third, although distinct from the
medical/health and comorbidity factors discussed elsewhere in this volume, social
and behavioral risk factors may have the potential to interact with health factors,
amplifying overall risk of depression among older adults.
As illustrated in Table 3.1, numerous potential risk factors/risk markers can be
subsumed under the major categories of demographic, social and lifestyle/behav-
ioral. However, critically, there has been considerable variability in how intensively
these factors have been studied in the literature to date with respect to late-life
depression risk. A number of studies have examined such late-life depression risk
factors more comprehensively. For example, Schoevers and colleagues [1] per-
formed a detailed analysis of several social and demographic factors and found that
female gender and spousal loss were major contributors to total risk of late-life
depression. Similarly, Smit et al. [2] reported that female gender, low educational
attainment, and low social support were significant predictors. Another study, by
Vink and colleagues [3], addressed multiple social and behavioral factors. Among a
cohort of 1,712 participants (aged 5585 years) in the Longitudinal Aging Study
Amsterdam with 9 years of prospective follow-up, these authors observed that fac-
tors that significantly predicted depression included age, widowhood, and education
level (where higher education was protective). Two other recent studies, conducted
by Lyness et al. [4] and Lenze al. [5], also comprehensively examined such risk fac-
tors but observed somewhat different findings: while high-risk factors such as sub-
threshold or sub-clinical affective symptoms were related to incident depression,
social and behavioral factors were not significantly independently related to
increased risk after accounting for other factors (Table 3.2).
3
Table 3.2 Studies of multiple demographic, social and/or behavioral risk factors and late-life depression
Study authors Study Risk factors Depression
(location) Year design Study population N assessed evaluation tools Study findings
Lyness et al. 2009 Cohort Primary care patients 65 617 Multiple SCID, HAM-D Those at high risk for incident depression
(Rochester, NY) years without major included those with minor or subsyndromal
depression depression, history of major or minor
depression, and functional disability. Social
and behavioral factors were not significantly
independently related to increased risk.
Schoevers et al. 2006 Cohort Nondepressed and 1,940 Multiple Geriatric Mental Recent loss of spouse and disturbed sleep
(Amsterdam, the nondemented participants State AGECAT were significantly associated with incident
Netherlands) of Amsterdam Study of the depression.
Elderly (age 65 years)
Vink et al. 2009 Cohort Participants of the 1,712 Multiple CES-D, HADS Factors that significantly predicted
(Amsterdam, the Longitudinal Aging Study depression over 9 years of follow-up
Netherlands) Amsterdam aged 5585 included age and widowhood; education
years level was protective.
Lenze et al. 2007 Cohort Patients 60 years 126 Multiple HAM-D, Participants with higher apathy scores at
(Pittsburgh, PA) admitted to hospital for Primary Care baseline were more likely to develop MDD
hip fracture Evaluation of (OR = 1.09, 95 % CI = 1.031.16, p = 0.003);
Social and Behavioral Risk Factors for Late-Life Depression
Mental other factors were not significantly

Disorders associated with MDD.
Harlow et al. 1991 Case- Widowed and married 545 Multiple CES-D Size of social network at baseline had a
(Chapel Hill, control women aged 6575 years consistent inverse association with
NC) depressive symptoms at 1 month (p < 0.05)
and 12 months (p = 0.06) of follow-up.
Recent bereavement and physical disability
were related to depression risk.
(continued)
21
Table 3.2 (continued)
22

Cole et al. 2003 Meta- Community residents 50 23,058 Multiple Structured Female gender, bereavement, sleep
(Montreal, analysis years interview or disturbance and disability were found to be
Canada) depression significant risk factors for depression.
rating scale
Blazer et al. 1991 Cross- Community residents 65 3,998 Multiple CES-D While age was positively associated with
(Durham, NC) sectional years CES-D score in the unadjusted analysis, it
was inversely related to depressive
symptoms after controlling for gender,
disability and cognitive impairment
(p < 0.01).
Green et al. 1992 Cohort Community residents 65 1,070 Multiple Diagnostic Incident depression over 3 years was found
(Liverpool, UK) years computer to be significantly associated with baseline
program smoking status, loneliness, female gender,
AGECAT recent bereavement, and lack of satisfaction
with life.
Schoevers et al. 2000 Cohort Community residents 65 1,940 Multiple GMS-AGECAT A bivariate analysis after 3 years of
(Amsterdam, the years follow-up showed that higher age, death of
Netherlands) spouse, and history of depression were
significantly associated with incident
depression. However, in the multivariate
analysis, age was no longer significantly
related.
A. Singh and O.I. Okereke
3 Social and Behavioral Risk Factors for Late-Life Depression 23
3.2 Demographic Factors and Late-Life Depression Risk
Groffen et al. [6] recently conducted an investigation among a sample of 4,809

participants from the Reykjavik Study (aged 6693 years). Similar to the findings
presented by Vink and colleagues [3], education level was related to depression risk:
participants with lower education levels were more likely to report depressed mood
in late-life than those with a college education (odds ratio [OR] = 1.87, 95 % confi-
dence interval [CI] = 1.352.58). Kim and Durden [7] found that having a college
degree was associated with lower levels of depressive symptoms in all age groups,
including older adults (p < 0.001).
Socioeconomic status (SES) variables have also been recognized as significant
predictors: Results from a meta-analysis by Lorant and colleagues [8] showed that
lower SES individuals had a greater odds of developing depression than those in the
highest SES group (OR = 1.24, p = 0.004); however, the studies involved in this
review did not focus on older populations. Kim and Durden [7] observed that the
association between income level and depressive symptoms was not consistent
across age groups: among individuals aged 65 and older, no difference in the change
in depression scores over time was found between the low- and high-income groups.
In the Reykjavik Study [6], lack of car ownership in midlife and history of early-life
food shortages were associated with incident depressed mood in later life.
While Lyness and colleagues [4] did not find an association between race and
depression in a study involving primary care patients, results from another cohort
study found both race and ethnicity to be related to subsequent development of
depressive symptoms. In the Health and Retirement Study [9] both black women and
Hispanic women reported significantly more symptoms of depression than white
non-Hispanic women (p < 0.001 for both), and Hispanic men had higher levels of
depressive symptoms than white non-Hispanic men (p < 0.05).
Female gender is a well-recognized risk factor for depression across all age
groups, and several studies have shown that female gender [1, 2, 10] is specifically
related to risk of late-life depression. Being of advanced chronological age [3, 11]
has also been related to risk of depression in some, but not all, studies. In one cohort
of older primary care patients, women had a significantly higher risk of developing
depression during the follow-up period than men [12]; a similar association was
observed in a cohort of community residents aged 65 and older [13]. Cole and
Dendukuri [10] performed a meta-analysis of studies involving middle-aged and
older adult community residents, and determined that female gender was a risk
factor for depression in this population (Pooled OR = 1.4, 95 % CI = 1.21.8), but
not old age. Blazer and colleagues [11] found a significant positive association
between older age and depressive symptoms in a sample consisting of community-
dwelling older adults; however, when potential confounders such as physical
disability, cognitive impairment, and gender were included in the analysis, the rela-
tionship between chronological age and depressive symptoms was reversed
(p < 0.01). A study by Schoevers and colleagues [14] had similar results: being in a
higher age stratum corresponded to a greater 3-year risk of incident depression in a
bivariate analysis (OR = 1.30, 95 % CI = 1.061.60), but this association was not
significant in a multivariate analysis. Thus, these findings suggest that higher inci-
dence of depression observed among the oldest-old may be explained by other rel-
evant factors. By contrast, the association of female gender with increased risk of
late-life depression has been observed to be a highly consistent finding.
Living alone has also been evaluated as a possible risk factor for late-life depres-
sion [15]. In the meta-analysis by Cole et al. [10], older adults who lived alone had
a greater odds of developing depression than those who did not, though the associa-
tion was not significant (Pooled OR = 1.7, 95 % CI = 0.64.7). Marital status was not
identified as a risk factor in this analysis, as there was no difference in the odds of
incident depression in married vs. unmarried individuals. Green and colleagues [12]
did not find living or marital status to be related to depression in a prospective study
of adults over age 65. Household status at baseline was predictive of depressive
symptoms after 2 years among middle-aged men and women in the Health and
Retirement Study [9], however; both single men who lived alone (p < 0.001) and
single men who lived with others (p < 0.01) had significantly greater levels of
depressive symptoms at a follow-up assessment than married men. Single women
living with children reported more depressive symptoms at follow-up than married
women (p < 0.01), though no difference in the outcome of interest was observed
between married women and those who were single and living alone. Thus, a criti-
cal factor to note when considering the literature on living alone and late-life depres-
sion risk is that living arrangement and marital status are very strongly correlated.
Therefore, research that gives attention to creating clear, mutually distinct catego-
ries of living and marital status among older persons (e.g., married, widowed and
living with others, widowed and living alone, divorced and living with others,
divorced and living alone), and then examines whether such status is independently
related to late-life depression risk, will be poised to offer more clarity on these ques-
tions (Table 3.3).
3.3 Social Factors and Late-Life Depression Risk
Numerous studies have delved into the contributions of social factors in late-life
depression risk. In an examination of marital bereavement, Turvey et al. [16] ana-
lyzed data among 5,449 participants aged 70 years from the Asset and Health
Dynamics Among the Oldest Old Study. Consistent with the strong effects of recent
spousal loss reported by Schoevers et al. [1], recently bereaved participants had
nearly nine times the odds of developing syndromal depression as married partici-
pants (OR = 8.8, 95 % CI = 5.114.9, p < 0.0001), and they also had significantly
higher risk of depressive symptoms 2 years after the spousal loss. Holley and col-
leagues [17] examined contributions of both stress levels and spousal loss to late-
life depression risk among 1,532 persons in the Changing Lives of Older Couples
study (mean age = 69 years). Both stress and spousal loss were independently asso-
ciated with onset of late-life depression. Furthermore, the observed relation between
3
Table 3.3 Studies of sociodemographic risk factors and late-life depression

Study authors Study Study Risk factors Depression
(location) Year design population N assessed evaluation tools Study findings
Groffen et al. 2013 Cohort Participants of 4,809 Education level, GDS-15 Participants with lower education levels were more
(Maastricht, the the Reykjavik SES in early/ likely to report depressed mood in late-life than those
Netherlands) Study mid-life with a college education (OR = 1.87, 95 % CI = 1.35
reexamined 2.58). Lack of car ownership in mid-life and
(aged 6693 early-life food shortages were also associated with
years) incident late-life depressed mood.
Kim et al. 2007 Cohort U.S. adults who 3,617 Education, CES-D College graduates in all age groups had lower levels
(Denver, CO) participated in income of depression than those with less education.
the Americans Participants with higher incomes had lower
Changing Lives depression scores than low-income participants until
(ACL) survey late in life, when the gap in depression levels
between these two groups converged (p for
interaction <0.05).
Lorant et al. 2003 Meta- Adults (mean 26,314 Socioeconomic DIS, GHQ Participants in the lowest SES group had a
(Brussels, analysis ages = 4255 status significantly greater odds of developing depression
Belgium) years) compared to those in the highest SES group
(OR = 1.24, p = 0.004).
Social and Behavioral Risk Factors for Late-Life Depression
Hughes et al. 2002 Cohort Adults aged 8,485 Living/ CES-D Both single men living alone and single men living
(Durham, NC) 5162 years in household with others had significantly greater levels of
the Health and status; race/ depressive symptoms after 2 years of follow-up than
Retirement ethnicity married men without children (p < 0.001 and p < 0.01,
Study respectively). Single women living alone did not have
higher levels of depressive symptoms than married
women at follow-up; however, single women living
with children did (p < 0.01). Black women and
Hispanic women reported significantly more
depression than white non-Hispanic women
(p < 0.001 for both), and Hispanic men had higher
25
levels of depressive symptoms than white non-

Hispanic men (p < 0.05).
stress and depression was stronger in the presence of cardiovascular risk factors
(CVRFs); however, no interactions between spousal loss and CVRFs were found.
Caregiving burden is well-recognized as a predisposing factor for depression
among older adults [18]. Many older persons are coping with physically and emo-
tionally challenging caregiving roles (e.g., caring for a spouse/partner with a serious
illness or with cognitive or physical decline). Additionally, many caregivers experi-
ence elements of grief, as they mourn the loss of relationship with or the decline of
valued attributes of their care recipients. Thus, in an recent example of selective
prevention (see Chap. 8), Schulz et al. [19] translated knowledge of caregiving bur-
dens role in late-life depression into a prevention trial. These investigators conducted
a two-group randomized controlled trial, testing the efficacy of a psychosocial inter-
vention for the informal caregivers of long-term care facility residentsin recogni-
tion of the fact that many such caregivers continue to provide considerable care and
support even after their care recipients have been placed in institutional settings.
Follow-up was conducted at 6, 12, and 18 months post-baseline. Although no statisti-
cally significant treatment effects were observed in caregiver depression, it was
observed that complicated grief was significantly lower for caregivers in the psycho-
social treatment condition. However, another recent trial [20] demonstrated signifi-
cant benefits for reducing depression among older caregivers. In the Resources for
Enhancing Alzheimers Caregiver Health (REACH) II randomized trial, investiga-
tors aimed to test the benefits of a multi-modal intervention (involving didactic
instruction, role-playing, skill developments in stress management and problem-
solving and telephone support) for reducing burden and depression of caregivers of
patients with Alzheimer disease (AD). Of 494 families initially enrolled, 177 fami-
lies (median caregiver age was 62 years) completed the 6-month program and had
pre- and post-intervention depression scores; depression scores demonstrated statis-
tically significant improvements upon program completion.
Concepts of social isolation have also been examined with regard to late-life
depression risk. For example, among 892 participants aged 65 years in the Ibadan
Study of Aging, Gureje et al. [13] found that women with a poor social network and
rural residential status were more likely to develop major depressive disorder (MDD)
than those without such status. Interestingly, a potential gender difference was
found, such that these associations were observed among women but not seen
among men. Harlow and colleagues [21] assessed the association between social
network and depressive symptoms in a study involving both married and recently
widowed women between the ages of 65 and 75 years; they found that number of
friends at baseline had an inverse association with CES-D (Centers for Epidemiologic
Studies Depression Scale) score after 1 month (p < 0.05) and 12 months (p = 0.06) of
follow-up. In a study that explicitly addressed the concept of loneliness, Jaremka
et al. [22] conducted a study relating this factor to late-life depression; importantly,
loneliness has been validated as a distinct construct, distinguishable among older
adults from depression. Among 229 participants (mean age = 70 years) in a cohort
of older adults caring for a spouse with dementia, loneliness (as measured by the
NYU scale) significantly predicted incident depression (p < 0.001).
Finally, social support has been identified as important to late-life depression

risk. For example, Cui and colleagues [23] found that low perceived social support
significantly predicted worsening depression status over a 2-year period among 392
primary care patients aged 65 years and above. Similarly, Cole et al. [24] examined
associations of social support to depression risk among 86 older medical inpatients,
aged 65 years and above. In their analysis, low emotional support was significantly
associated with onset of depression; interestingly, other social factors examined in
this studybirth outside of the country and infrequent contact with family/children
in the past monthwere also significantly related to development of depression
(Table 3.4).
3.4 Lifestyle/Behavioral Factors and Late-Life

Depression Risk
The area of lifestyle and behavioral factors is perhaps most promising with regard
to late-life depression prevention because these tend to be the most readily modifi-
able. For example, while it may not be possible to remediate physical disability,
eliminate certain medical conditions, or alter ones childhood educational attain-
ment, behaviors such as smoking or dietary pattern adherence are more readily
modifiable or potentially avoidable. With regard to smoking behavior, Weyerer et al.
[25] examined this issue in a cohort of 138 older patients recruited from primary
care practices; after adjustment for potential confounding variables, being a current
smoker was significantly related to incidence of major depression. Results from a
cohort study involving elderly community residents also showed a significant asso-
ciation between being a smoker at baseline and depression after 3 years of follow-
up [12]. Saunders and colleagues [26] reported comparable findings with alcohol
drinking behavior as the predictor. Among 701 community-dwelling adults aged 65
years and above, the authors found a significant association between prior heavy
alcohol consumption and late-life depression among men: compared to those who
were not heavy drinkers, men with a history of heavy drinking had a nearly fourfold
higher odds of being diagnosed with depression (OR = 3.7, 95 % CI = 1.310.4,
p < 0.05).
Health-promoting behaviors such as physical activity and adherence to healthy
dietary patterns may decrease ones risk of developing depressive symptoms late in
life. For example, Hodge and colleagues [27] observed that middle-aged and elderly
adults who followed a Mediterranean dietary pattern had lower levels of psychologi-
cal distress after 12 years than those who did not adhere to this diet (OR for tertile 3
vs. tertile 1 = 0.72; 95 % CI = 0.540.95). In the Alameda County Study [28], adults
aged 50 and older who had higher scores on a physical activity scale at baseline had
a reduced likelihood of developing depression over 5 years of follow-up (OR = 0.83,
95 % CI = 0.730.96). Although overweight/obesity can be conceptualized as a
health/medical issue, weight itself is at least subject to modification (e.g., through
weight control activities of diet modification or exercise) and, thus, might also be
Table 3.4 Studies of social/psychological risk factors and late-life depression
28

Cui et al. 2008 Cohort Primary care patients 392 Social SCID, Risk factors associated with worsening depression
(Rochester, 65 years support HAM-D, LIFE status over the 2-year period included low perceived
NY) social support.
Cole et al. 2008 Cohort Nondepressed medical 86 Social Diagnostic Birth outside of the country, fewer than two children
(Montreal, inpatients 65 years network, Interview seen in the past month, and inadequate emotional
Canada) social support Schedule support were all significantly associated with onset of
depression.
Jaremka et al. 2013 Cohort Older adults caring for 229 Loneliness BDI Loneliness, defined by the NYUL scale, was found to
(Ohio) a spouse with dementia (NYU scale) significantly predict incident depression (p < 0.001).
(mean age = 69.7 years)
Gureje et al. 2011 Cohort Participants 65 years 892 Social CIDI Women had a significantly greater risk of developing
(Ibadan, of the Ibadan Study of network MDD over the 39-month follow-up period than men
Nigeria) Aging (HR = 1.63, 95 % CI = 1.302.06). Women who had a
poor social network and rural residence were more
likely to develop MDD than those who did not, but
this association was not found among men.
Holley et al. 2006, Cohort Older adults from the 1,532 Stress, CES-D Stress and spousal loss were independently associated
(Louisville, 2007 Changing Lives of Spousal loss with onset of late-life depression. The observed
KY) Older Couples study relation between stress and depression was stronger
(mean age = 69 years) in the presence of cardiovascular risk factors
(CVRFs); however, no interactions between spousal
loss and CVRFs were found.
Turvey et al. 1999 Cohort Subjects 70 years 5,449 Spousal loss CIDI, CES-D Recently bereaved participants had nearly nine times
(Iowa City, from the Asset and the odds of developing depression as married
IA) Health Dynamics participants (OR = 8.8, 95 % CI = 5.114.9,
Among the Oldest Old p < 0.0001).
Study
considered a lifestyle issue. Almeida et al. [29] addressed this issue in a study exam-
ining the contribution of weight and later-life depression risk. These investigators
found that obese men were more likely than non-obese (body mass index [BMI] < 30)
men to develop depression (HR = 1.31, 95 % CI = 1.051.64). Consistent with these
results, presence of the metabolic syndrome was also found to increase risk of
incident depression (HR = 2.37, 95 % CI = 1.603.51).
Finally, leisure-time activities are also important to study with regard to late-life
depression risk, as these too are readily modifiable behaviors. For example, Magnil
et al. [30] examined such activities among a sample of 302 primary care patients
aged 60 years. The authors observed that those who lacked leisure activities had
an increased risk of developing depressive symptoms over the 2-year study period
(OR = 12, 95 % CI = 1.1136, p = 0.041).
For readily apparent reasons, there has not been an abundance of randomized
trials that have involved direct modification of many of the above-described social
and behavioral factors for the purposes of assessing effects on late-life depression
risk. For example, people could never be randomized to spousal loss, smoking, or
low educational attainment, as this would be unethical as well as infeasible.
However, one could foresee interventions to reduce stress, improve social support/
social engagement, enhance leisure-time activities, or encourage healthful behav-
iors (e.g., smoking cessation and physical activity), with a view toward mitigating
late-life depression risk. Indeed, Underwood et al. [31] recently conducted a ran-
domized trial of daily physical activity and exercise sessions among 891 older care
home residents (aged 65 years). Although the exercise intervention did not have a
statistically significant beneficial effect of depression prevention after 12 months of
follow-up, the estimates were in the direction of lower odds of depression in the
intervention group vs. control group (OR = 0.76, 95 % CI 0.531.09). Thus, future
depression prevention trials of a similar nature would be important contributions
(Table 3.5).
3.5 Future Directions
As noted above, an important future direction in addressing social and behavioral

risk factors in late-life depression is to make more progress in trials that aim to alter
those risk factors that are actually modifiable. Furthermore, it will be important to
perform future investigations that examine key interactions of these factorsfor
example, whether stress or low social support has differential impacts on depression
risk by gender, culture, or race/ethnicity. Finally, additional research ideally can be
undertaken to address social and behavioral risk factors that have been relatively
understudied to date in late-life, such as problem alcohol drinking, substance use,
and the roles of personality styles and traits (e.g., optimism or resilience).
Table 3.5 Studies of lifestyle/behavioral risk factors and late-life depression
30
Study authors Study Risk factorsDepression

Magnil et al. 2013 Cohort Patients 60 years of 302 Leisure-time PRIME-MD; Subjects who lacked leisure activities had an
(Gothenburg, primary care center in activities MADRS-S increased risk of developing depressive symptoms
Sweden) Gothenburg over the 2-year period, measured by MADRS-S
(OR = 12, 95 % CI = 1.1136, p = 0.041).
Underwood 2013 RCT Eldercare home 891 Daily physical GDS-15 The exercise intervention did not have an effect on
et al. residents 65 years activity, depression prevention. After 12 months of follow up,
(Coventry, exercise the intervention group did not have significantly
UK) sessions lower odds of having depression than the control
group (OR = 0.76, 95 % CI: 0.531.09).
Hodge et al. 2013 Cohort Participants of the 8,660 Mediterranean Kessler Participants whose Mediterranean diet scores were
(Carlton, Melbourne diet score Psychological in the highest tertile were significantly less likely to
Australia) Collaborative Cohort computed Distress Scale experience psychological distress than those whose
Study aged 5069 from FFQ (K10) scores were in the lowest tertile (OR = 0.72; 95 %
years CI = 0.540.95).
Weyerer et al. 2013 Cohort Patients 75 recruited 2,512 Smoking GDS-15 After adjustment for confounding variables, current
(Mannheim, from 138 primary care smoking status was significantly associated with
Germany) practices in Germany incidence of depression.
Almeida et al. 2009 Cohort Men 65 years living 12,066 Body mass ICD-10 Obese men were more likely than non-obese men
(Perth, in Perth metropolitan index diagnosis (BMI < 30) to develop depression (HR = 1.31, 95 %
Australia) area CI = 1.051.64).
Saunders et al. 1991 Cohort Random sample of 701 Alcohol GMS A significant association was found between past
(Liverpool, community residents drinking heavy alcohol consumption and late-life depression
UK) aged 65 years behavior among men. Men in the study with a history of
heavy drinking had a higher odds of being diagnosed
with depression than men who were not heavy
drinkers (OR = 3.7, 95 % CI = 1.310.4, p < 0.05).
Strawbridge 2002 Cohort Adults aged 5094 1,947 Physical DSM-IV Participants with higher physical activity levels at
et al. years who participated activity scale criteria baseline were significantly less likely to develop
(Berkeley, in the Alameda County depression over 5 years (OR for 1-point
CA) Study increase = 0.83, 95 % CI = 0.730.96).
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Prevention of Depression in Medical
Conditions 4
Liming Dong and Joseph J. Gallo
Abstract
In this chapter, we provide an overview of the relationship between physical
health and depression, including excess disability and mortality associated with
depression, and discuss what we know about prevention of depression in the
context of medical conditions such as diabetes and cardiovascular disease. We
describe a conceptual framework linking depression and medical illness, with a
literature review of randomized controlled trials of prevention that recruited non-
depressed persons with at least one physical disorder. Most of the reported stud-
ies, though not all, showed that pharmacologic or non-pharmacologic strategies
can reduce rates of depression. Methodologic considerations and future direc-
tions are described. Prevention of depression in the context of medical conditions
is a new field with implications for research, policy, and practice.
Keywords
Medical comorbidity Mortality Primary health care Diabetes Cardiovascular
disease Cancer
L. Dong J.J. Gallo M.D., M.P.H. (*)

Department of Mental Health, Bloomberg School of Public Health,
Johns Hopkins University, 624 North Broadway,
Room 792, Baltimore, MD 21205, USA
e-mail: Jgallo2@jhu.edu

34 L. Dong and J.J. Gallo
4.1 Laying the Groundwork for Prevention
While groundbreaking work has been carried out, prevention of depression in medical
contexts remains largely unexplored territory. While an ounce of prevention is
worth a pound of cure seems self-evident, as Benjamin Franklin wrote in his
famous almanac, in medicine it has not always been easy to demonstrate empiri-
cally that prevention does work as intended. Nevertheless, the personal and soci-
etal costs of depression are so great that we need to move forward even in the face
of uncertainty. In the field of cardiovascular health, the past decades have seen the
concepts of risk factors and prevention become widely accepted. The field of
mental health and psychiatry lags behind, but the idea of prevention is taking hold
as evidenced by the chapters in this book.
Our starting point for prevention is major depression as defined in the American
Psychiatric Associations Diagnostic and Statistical Manual (DSM). We recognize
that, particularly for older adults with medical comorbidity, major depression as a
focus may have some problems because even depressive symptoms that do not meet
clinical diagnostic criteria are detrimental to health and functioning. Minor depres-
sion is particularly common among older adults and is associated with medical
comorbidity [15]. Racial and ethnic minorities tend to report greater symptoms of
general distress and higher burden of medical comorbidity [6, 7] but are less likely
to meet diagnostic criteria for major depression relative to non-Hispanic Whites
[8, 9]. Depression and mortality are linked even when symptoms are relatively mild
[1012] or when psychological factors that are not included in standard criteria are
studied (e.g., hopelessness, pessimism) [13]. So while it seems obvious in most
work that the goal is prevention of major depression, the first question that must be
answered in prevention research on depression and medical comorbidity is: what is
it we are trying to prevent?
Even if we agree to restrict our attention to major depression, investigators seek-
ing to show that an intervention prevents major depression face significant chal-
lenges. The number of people needed in a study to show an effect size of any
significance may be impractical. A strategy to make the sample size requirements
more manageable is to direct the intervention at a high-risk group (i.e., increasing
the number of cases of depression expected so that a preventive intervention has
room to show an effect). Examples of such a high risk strategy include depression
associated with senile macular degeneration [14], poststroke depression [15], and
interferon-induced depression [16]. Prevention studies must consider the target
population (e.g., persons with recent myocardial infarction or diabetes) and the set-
ting (e.g., the coronary care unit or primary care settings) to realize their potential
public health impact. In clinical and community settings where prevention strate-
gies would be deployed, depression symptoms may be difficult to recognize, com-
plicating exclusion of cases (in studies of selective prevention) or in identification
of outcomes (in studies of indicated prevention). So in setting forth our ideas we
must go in with our eyes wide open: things are not so simple as Franklins maxim
would imply.
4 Prevention of Depression in Medical Conditions 35
4.2 The Intersection of Physical Health and Depression
In this section, we discuss the links between physical health and depression among
older adults, links that are potential targets for interventions that may interrupt the
connection between physical conditions and depression. In contrast to depression in
childhood and youth when genetic and developmental vulnerabilities play a signifi-
cant role in the development of depression, the development of late-life depression
is largely attributed to its interactions with acquired factors, especially medical
illness [17, 18]. An analysis of the WHO World Health Survey indicated that the
prevalence of depression among medical patients ranged from 9.3 to 23.0 %, signifi-
cantly higher than that in individuals without medical conditions [19]. Wells et al.
[20] found in the Epidemiologic Catchment Area Study that the risk of developing
lifetime psychiatric disorders among individuals with at least one medical condition
was 27.9 % higher than among those without medical conditions. Meanwhile, the
prevalence of any medical condition among individuals with psychiatric disorder
was 15 % higher than among those without a lifetime psychiatric disorder [21].
The bidirectional association between medical illnesses and depression acts
through physiological changes, psychological changes, and a set of common factors
(e.g., disability, pain, stress, risk behaviors, loneliness, and hopelessness; see
Fig. 4.1) that could be either consequences or causes of physical disorders and
depression. Adverse effects of pharmacological treatment for physical disorders
could induce major depression, and medications for major depression may also
cause medical conditions, such as falls, hip fractures, and obesity.
4.2.1 Disability
Disability is defined by the International Classification of Functioning, Disability

and Health (ICIDH-2) as an umbrella term for impairments, activity limitations or
participation restrictions [22]. Despite declining trends in chronic disability among
US adults aged 65 and older, approximately one-fifth were disabled in 2005 [23].
The high prevalence of physical disability among older adults is mainly attributed
to chronic diseases [24]. Depression and disability mutually reinforce the risk
of each other, and adversely affect disease progression and prognosis [21, 25].
Fig. 4.1 Conceptual framework linking physical and mental health

On the one hand, disability caused by medical conditions serves as a risk factor
for depression [26]. When people lose their normal sensory, motor, cognitive,
social, or executive functions, especially in a short period of time, they can become
very frustrated or depressed. Inability to perform daily tasks as before decreases
self-esteem, reduces independence, increases the level of psychological stress, and
creates a sense of hopelessness. On the other hand, depression increases the risk for
disability. Negative interpretation, attention bias, and learned hopelessness of
depressed persons may increase risky health behaviors that exacerbate physical dis-
orders or disability. Meanwhile, depression-related cognitive impairment also affects
role performance and leads to functional disability [25]. For example, Egede [27]
found in the 1999 National Health Interview Survey that the risk of having functional
disability among patients with the comorbidity of diabetes and depression were
approximately 2.55 times higher than those with either depression or diabetes alone.
4.2.2 Pain
A leading cause of disability among medical patients is pain and pain-related fears
[28]. Pain is an unpleasant perception caused by diseases or injuries, which is particu-
larly common among the elderly, especially institutionalized older adults [29].
The main medical reasons include back injury, arthritis, and cancer [30, 31]. Although
a large proportion of pain complaints can be attributed to physiological changes from
physical disorders, psychological factors (e.g., attention, interpretation, and coping
skills) play an important role in perception of pain, as indicated in Fig. 4.1 [32].
Individuals with cognitive bias and poor coping strategies report more intense and
persistent pain, as well as depressive symptoms [31, 33]. Bair et al. [31] indicated in a
literature review that the prevalence of pain was higher among depressed patients than
non-depressed patients, and the prevalence of major depression was also higher
among pain patients comparing to those without pain complaints. The comorbidity of
depression and pain may be explained by shared biological pathways [31]. Decreases
in neurotransmitters among depressed patients (such as serotonin) amplify nocicep-
tive signals and, therefore, increase the frequency and severity of pain symptoms [31].
Consistently, over half of the chief complaints from depression patients in primary
care were somatic symptoms, mainly pain complaints, which impose difficulties for
primary care physicians in recognizing mild or moderate depression and in preventing
the occurrence of major depression [31].
4.2.3 Stress
While disability and pain are sources of stress, so is being diagnosed with a medical
condition. Being diagnosed with diseases and undergoing treatments increase
patients psychological stress, especially for those who do not have positive percep-
tions, effective coping strategies or adequate social support [34]. According to the
diathesis stress model, major depression will occur once the magnitude of perceived
stress increases to an extent at which ones threshold for the disorder is reached [35].
Meanwhile, major depression is found to be associated with stress-induced activa-
tion of the inflammatory response (Fig. 4.1) that produces a series of physiological
and psychological effects [36]. Immune activation releases cytokines (e.g., TNF
and IL-1) in the brain that may mediate the link between medical conditions and
depressive symptoms [36]. Hormonal response is another important stress-related
biological pathway that links physical disorders and depression [37]. Maladaptation
in stress response may cause the dysregulation of the hypothalamic-pituitary-
adrenal (HPA) axis, characterized by elevated levels of cortisol and corticotropin-
releasing hormone (CRH) [37]. Increased cortisol level is not only associated with
stress and emotional disturbance but also is implicated in progression of a variety of
medical conditions, such as cardiovascular disease, type 2 diabetes mellitus, ulcers,
and loss of bone density [37, 38].
4.2.4 Risk Behaviors
Risk behaviors (e.g., smoking, alcohol and drug abuse, poor adherence to treatment,
malnutrition, and physical inactivity) could be maladaptive coping responses to
stress, or unhealthy lifestyles continued from earlier life stages. For example, physi-
cal inactivity, as a consequence of depression, is also associated with increased risk
for coronary heart disease, diabetes, stroke, and cancer [3942]. Mattson [43] indi-
cated in a review that physical activity activates adaptive stress responses in neu-
rons, produces protective factors such as brain-derived neurotrophic factor (BDNF)
that increase the brains capacity to buffer stress, and therefore decreases the risk for
depression as well as other brain disorders among older adults. Findings from the
Alameda County Study also supported that physical activity was a protective factor
for subsequent depression among adults aged 50 and over [44]. People who partici-
pated in physical activities were more likely to have less risky health behaviors,
such as smoking and overdrinking [44]. Alcohol use has more serious adverse
health effects on older adults than other age groups, since aging-related physiologi-
cal changes (e.g. reduced liver detoxification and renal clearance) affect alcohol
metabolism, increase the blood concentration of alcohol, and magnify negative
consequences. More importantly, alcohol interacts with a variety of frequently pre-
scribed medications potentially influencing both treatment and adverse effects.
4.2.5 Loneliness
Loneliness is the perceived isolation from ones surrounding relationships.

According to the Health and Retirement Study, approximately one-fifth of the US
adults aged 65 and older experienced loneliness [45]. It is considered as an indepen-
dent risk factor for depression [46, 47], and has been demonstrated to be associated
with low physical activity, increased cardiovascular risks, hyperactivity of the hypo-
thalamic-pituitary-adrenal axis, and activation of immune response [4851].
Physical disorders and aging-related functional decline, such as hearing loss and
vision impairments, limit individuals mobility and capability for social involve-
ment to different extents. A cross-sectional study conducted in the Finnish older
population indicated that poor health conditions and functioning impairments were
associated with higher risk for loneliness, and medical illness was also reported as
one of the most common causes of loneliness [52]. Older adults may view loneli-
ness as an important factor in the expression of depression [53].
4.2.6 Hopelessness
Hopelessness is a key concept of major depression [54], and also an independent

risk factor of suicidal ideation [55]. According to the hopelessness theory of depres-
sion, with the presence of negative life events (e.g., experiencing physical disor-
ders), depression-prone individuals tend to process information with bias, attribute
these events to global, constant, and internal causes, and make adverse inferences
[56]. Hopelessness is also conceptualized as a distinct concept independent of
depression, acting as a mediator of the association between physical disorders and
depression [57]. Elevated hopelessness was found to be associated with the onset of
myocardial infarction, cancer, and hypertension, and with mortality [58, 59]. More
commonly, hopelessness can be a consequence of physical disorders among medi-
cal patients, especially those with terminal illness and life-threatening conditions
[57]. Hopelessness reduces expectations for the future, and negatively affects judg-
ment for making medical and behavioral decisions, including non-adherence to
medical regimens or engaging in unhealthy behaviors.
4.2.7 Adverse Drug Effects
Due to age-related changes in pharmacokinetics and pharmacodynamics, older

adults are a vulnerable population to iatrogenic diseases caused by adverse drug
effects. Drugs for treating medical conditions could affect neurotransmitters in the
brain through biological pathways, and also may have a psychological impact on
patients by causing somatic symptoms [60]. Celano et al. [60] summarize major
categories of medications that have the potential to induce depression among medi-
cally ill patients, including neurologic medications, cardiovascular medications,
anti-infective agents, oncologic medications, and miscellaneous medications.
Although cases of drug-induced depression were reported for a variety of drugs, few
prospective studies with good internal validity were conducted to examine the true
incidence [60]. Even so, physicians are recommended to evaluate medical patients
risk for depression, avoid depressogenic drugs for patients with prior or current
depression episodes, and monitor for drug-induced depression [60]. Similarly, anti-
depressants can also cause physical disorders among older adults, such as falls, hip
fractures, weight gain, and obesity, which may in turn increase the severity of
depressive symptoms [6163]. Adverse drug events are frequently due to failure to
adjust dosage or to account for drugdrug interactions in older adults [64].
4.3 Mortality and Depression
Co-occurring depression and medical conditions are associated with more functional
impairment and mortality than expected from the severity of the medical condition
alone. For example, depression accompanying diabetes confers increased functional
impairment [27], complications of diabetes [65, 66], and mortality [6771]. Frasure-
Smith and colleagues highlighted the prognostic importance of depression among
persons who had sustained a myocardial infarction (MI), finding that depression
was a significant predictor of mortality at both 6 and 18 months post MI [72, 73].
Subsequent follow-up studies have borne out the increased risk conferred by depres-
sion on the mortality of patients with cardiovascular disease [10, 74, 75]. Over the
course of a 2-year follow-up interval, depression contributed as much to mortality
as did myocardial infarction or diabetes, with the population attributable fraction of
mortality due to depression approximately 13 % (similar to the attributable risk
associated with heart attack at 11 % and diabetes at 9 %) [76]. Investigators seeking
to understand the biological mechanisms linking depression and medical conditions
have focused on cardiovascular, immunologic, inflammatory, metabolic, and neuro-
endocrine pathways [77, 78].
Several intervention studies (i.e., among samples of older adults with depres-
sion) have examined mortality as an outcome [7982]. In ENRICHD (Enhancing
Recovery in Coronary Heart Disease) taking a selective serotonin reuptake inhibitor
was associated with reduction in the risk of all-cause mortality [83], as was partici-
pation in group plus individual therapy [84] in secondary analyses that ignored ran-
domization. SADHART (Sertraline Antidepressant Heart Attack Randomized Trial)
reported a statistically non-significant beneficial trend on combined cardiovascular
outcomes that included death at 24 weeks [82]. PROSPECT (Prevention of Suicide
in Primary Care Elderly Collaborative Trial) reported diminished mortality after 8
years of follow-up among older persons in practices randomized to a depression
care management program [79].
4.4 Evidence on Prevention of Depression in Medical

Comorbidity
Universal, selective, and indicated prevention strategies apply to mental health [85, 86].
Universal prevention strategies are intended to reach the entire population, without
regard to individual risk factors. For example, every person, without screening, in a
community or practice might be provided with prevention skills. We do not consider
universal prevention strategies here, since persons with medical conditions are de
facto subgroups of the population at increased risk. Selective prevention strategies
target subgroups of the general population that are determined to be at risk, for
example, persons who have a medical condition. Indicated prevention interventions
identify individuals who are experiencing depressive symptoms, but do not meet
criteria for major depression. This potentially includes many persons who have
medical conditions, since depressive symptoms are so common.
We carried out a literature review to identify prevention intervention trials with a

focus on adults with medical comorbidity. Included randomized controlled trials
of prevention recruited non-depressed patients with at least one physical disorder.
We did not incorporate trials primarily directed at treatment of existing major depres-
sion (e.g., in the context of diabetes [87] or cardiovascular disease [80]), prevention of
depression recurrence (e.g., in the context of diabetes [88, 89]), or reduction in depres-
sive symptoms among both depressed and at-risk patients (e.g., in the context of car-
diovascular disease [90] or cancer [91, 92]). Ideally, we would have required
investigators to exclude persons who met criteria for major depression since persons
who have major depression are no longer at risk. Rather than using diagnostic criteria,
investigators may have excluded persons whose depression scores were above a
threshold (e.g., using the Hamilton Depression Rating Scale [93, 94], the Hospital
Anxiety and Depression Scale-depression subscale [95], or the Geriatric Depression
Scale [96]. While it is true that persons whose scores were above a threshold would be
more likely to meet criteria for major depression, persons below the threshold could
still meet criteria for minor depression. The implication is that we would call a study
indicated for persons with minor depression, but selective for persons who do not
have depression. Investigators sometimes did not report the information required to
make this distinction. So we decided to categorize interventions in the table based on
our best justification for each individual study. We did not include studies specifically
tied to the prevention of depression associated with the administration of alpha-inter-
feron or similar substances. We summarize prevention trials meeting our inclusion
criteria in Table 4.1 according to whether we categorized as indicated or selective
prevention (we did not find any studies we would consider universal prevention in
association with medical conditions).
4.4.1 Indicated Prevention Trials
Five studies of indicated prevention trials involved persons who had some depressive
symptoms but did not meet criteria for major depression (Table 4.1). In four studies,
investigators describe sample selection based on presence of medical conditions with-
out specifying a specific medical condition. All employed interventions that were non-
pharmacologic [97100], one examined both pharmacologic and non-pharmacologic
interventions [99] and all were effective in reducing depressive symptoms. One study
of patients with HIV/AIDS prescribed dehydroepiandrosterone, DHEA [101].
Targeting patients with medical comorbidity but without a focus on a specific condition
may make sense from a health services or public health point of view because the focus
is on the venue in which people are receiving care (e.g., primary care) and because
most patients present with multiple medical conditions [102].
4.4.2 Selective Prevention Trials
Selective prevention trials focus on specific medical conditions. Seven of the studies
with a focus on a medical condition were to prevent depression in patients with
stroke [9395, 103106]. While cardiovascular disease and diabetes are common
4
Table 4.1 Indicated and selective prevention studies

Intervention
Study Sample Drug Non-drug Description Setting Findings
Indicated prevention
Disease not specified
vant 170 adults aged 75 and X Intervention: a preventive Primary At 12 months, the intervention group had 51 %
Veer-Tazelaar older with sub- stepped-care program care lower risk of major depression or anxiety than in
et al. [97]; threshold depression Control: usual care the control group (RR, 0.49; 95 % CI, 0.24
vant or anxiety 0.98). At 24 months, the odds of having major
Veer-Tazelaar depression or anxiety in the intervention group
et al. [130] was 62 % lower than in the control group (OR,
0.38; 95 % CI, 0.190.76)
Ciechanowski 138 chronically X Intervention: the PEARLS Community The odds of having 50 % or more reduction in
et al. [98] medically ill adults PST, social and physical depressive symptoms in the intervention group
aged 60 and older with activation, and potential was 5.21 times higher than in the control group
minor depression or recommendations to patients (OR, 5.21; 95 % CI, 2.0113.49). The odds of
Prevention of Depression in Medical Conditions
dysthymia physicians regarding achieving depression remission in the intervention

antidepressant medications group was 4.96 times higher than in the control
Control: usual care group (OR, 4.96; 95 % CI, 1.7913.72)
Williams 415 primary care X X Intervention: SSRI, Primary Among dysthymia patients, mental health
et al. [99] patients aged 60 and paroxetine or PST-PC care functioning was improved by paroxetine for those
older with minor Control: placebo with high or intermediate baseline functioning
depression or levels, but not significantly improved by
dysthymia PST-PC. Among minor depression patients,
mental health functioning was improved by both
paroxetine and PST-PC for those whose baseline
functioning was in the lowest tertile
Miranda and 150 medical patients X Intervention: CBT Primary The intervention was effective in reducing
Munoz [100] aged between 18 and Control: no-intervention or a care depressive symptoms (F = 3.72;
69 with minor 40-min videotape P = 0.01),somatic symptoms (F = 4.33; P = 0.005)
depression and missed primary care appointments (F = 4.5;
41
P = 0.05)
(continued)
42
Intervention
HIV/AIDS
Rabkin et al. 145 HIV positive X Intervention: DHEA Hospital DHEA was effective in reducing depressive
[101] patients aged between Control: placebo symptoms in both intent-to-treat analysis and
18 and 70 with completer analysis, where the response rates
persistent dysthymia were 56 % (DHEA group) versus 31 % (placebo
or subsyndromal group), and 62 % (DHEA group) and 33 %
depression for at least (placebo group) respectively. DHEA was safe
3 months and acceptable, demonstrated by low rates of
adverse events and attrition
Selective prevention
Stroke
Tsai et al. 92 patients with first X Intervention: SNRI, Hospital Milnacipran was effective and safe in preventing
[93] or recurrent ischemic milnacipran poststroke depression. The incidence rate of
stroke within the past Control: placebo DSM-IV major depression was 2.22 % in the
4 weeks intervention group, and 15.22 % in the control
group (P < 0.05)
Robinson 176 patients aged X X Intervention: SSRI, Hospital Patients in the placebo group were more likely
et al. [103] between 50 and 90 escitalopram or PST to develop major or minor depression than in
with hemispheric, Control: placebo both the escitalopram group (HR, 4.5; 95 % CI,
brain-stem or 2.48.2) and the PST group (HR, 2.2; 95 % CI,
cerebellar stroke 1.43.5) after adjustment for history of mood
within the past 3 disorders and potential confounders. In the
months intention-to-treat analysis, escitalopram
remained superior to placebo (HR, 2.2; 95 % CI,
1.23.9), but PST was not associated with a
significant difference from placebo (HR, 1.1;
95 % CI, 0.81.5)
L. Dong and J.J. Gallo
4
Almeida et al. 111 patients with acute X Intervention: SSRI, sertraline Hospital Sertraline was not found to be effective in
[95] ischemic or Control: placebo preventing 6-month depression. The incidence
hemorrhagic strokes of depression was 16.7 % in the intervention
within 2 weeks group and 21.6 % in the control group (RR, 0.8;
95 % CI, 0.32.1). The discontinuation rates
were high in both intervention group (51.8 %)
and placebo group (47.3 %)
Niedermaier 70 patients with X Intervention: NaSSA, Hospital Mirtazapine was effective in preventing
et al. [104] immediate ischemic mirtazapine poststroke depression. The incidence of DSM-IV
stroke Control: placebo depression was 5.7 % in the intervention group
and 40 % in the placebo group (risk difference,
34.3 %; 95 % CI, 52.2 to 16.3 %)
Rasmussen 137 patients with acute X Intervention: SSRI, sertraline Hospital Sertraline was effective and well tolerated in
et al. [94] ischemic stroke within Control: placebo preventing depression. The incidence of
the past 4 weeks depression based on HAM-D17 (>18) was 8.2 %
in the intervention group and 22.8 % in the
control group. The incidence of depression
based on HAM-D6 (9) was 11.5 % in the

intervention group and 28.1 % in the control
group
Narushima 48 patients aged X Intervention: nortriptyline or Hospital In completer analysis, the incidence of
et al. [105] between 18 and 85 SSRI, fluoxetine depression in the combined intervention group
with acute stroke Control: placebo (7.7 %) was significantly lower than that in the
within 6 months placebo group (33.3 %) during the 3-month
treatment period. In intention-to-treat analysis,
no significant difference in depression incidence
was found across groups in this period. 6 months
after discontinuing treatment, the incidence of
depression in the combined intervention group
was significantly higher than in the placebo
group (P = 0.047)
(continued)
43
44
Intervention
Palomaki 100 patients aged X Intervention: Mianserin Hospital Prevalence of depression and severity of
et al. [106] under 71 with acute Control: placebo depressive symptoms were not significantly
ischemic stroke within different between intervention and control group
1 month at all time points. However, there was some
improvement on the HAM and BDI among
adults aged over 56 and males in the
intervention group
Cancer
Komatsu 82 women aged under X Intervention: An oncology Hospital There were no significant differences between
et al. [108] 80 with primary breast nurseguided patient the intervention group and control group in
cancer, surgically education and support group anxiety and depressive symptoms, or quality of
treated and prescribed plus CBT life
for adjuvant therapy Control: usual care
Pitceathly 465 patients aged X Intervention: Immediate or Hospital The intervention effects differed by patients risk
et al. [109] between 18 and 70 delayed (8 weeks after levels. Among high-risk patients, individuals in
with newly diagnosed starting cancer treatment) the intervention group were less likely to
cancer, prescribed psychological intervention develop anxiety or depression than those in the
chemotherapy or Control: usual care control group (OR, 0.54; 95 % CI, 0.291.00).
radiotherapy, and Among low-risk patients, the difference between
expected to live for at groups was not significant (OR, 1.50; 95 % CI,
least 2 years 0.514.43)
Lydiatt et al. 28 patients aged 19 X Intervention: SSRI, Hospital Citalopram has the potential in preventing
[110] and over with newly citalopram depression. The incidence of depression was
diagnosed or recurrent Control: placebo 50 % in the treatment group, which was not
head-and-neck cancer significantly different from that of 17 % in the
and treated beyond control group (P = 0.17). However, the CGI-S
limited excision scale indicated that 60 % patients in the placebo
group were at least mildly ill, while only 15 %
in the intervention group were (P = 0.04)

4
Petersen and 53 women with newly X Intervention: relaxation and Hospital The intervention significantly reduced total
Quinlivan diagnosed counseling HADS scores (P = 0.002), anxiety subscale
[111] gynecological cancer Control: usual care (P = 0.001) and moderate depression subscale
and primarily treated (P = 0.02) scores of the HADS, the total
with surgery GHQ-28 scores (P < 0.02), the somatization,
anxiety and personality development subscale
scores of GHQ-28 (all P < 0.02), but not the
major depression subscale score of GHQ-28
Arthritis
Sharpe et al. 53 patients aged X Intervention: CBT plus Hospital The intervention significantly reduced
[113] between 18 and 75 routine medical management depressive symptoms and C-reactive protein
with a less than 2-year Control: standard care levels at posttreatment, and significantly reduced
history of definite or (routine medical depressive symptoms and improved joint
classical rheumatoid management) involvement at 6-month follow-up
arthritis (seropositive)
Phillips [114] 202 African Americans X Intervention: Community- Community The intervention significantly improved
aged between 67 and based disease education and participants arthritis knowledge (P < 0.05),
75 with both pain management medical social support (P < 0.01), and depressive
osteoarthritis and Control: nondisease-related symptoms (P < 0.01) 1 year after program
rheumatoid arthritis, program completion. The effects sustained to the second
and experienced year after program completion
arthritis-related
chronic pain
Diabetes and rheumatic diseases
de Jonge 100 patients with high X Intervention: Multifaceted Hospital The incidence of major depression was 36 % in
et al. [115] level of case nurse-led intervention the intervention group, comparing to 63 % in the
complexity (65 with Control: usual care control group (P = 0.02). The preventive effects
rheumatic diseases and were significant among subjects without severe
35 with diabetes) pain (P = 0.04), or with baseline CES-D above
20 (P = 0.02)
(continued)
45
46
Intervention
Age-related macular degeneration (AMD)
Rovner et al. 206 patients aged 65 X Intervention: PST Hospital PST was effective in preventing depression in
[116] and over with newly Control: usual care the short term. The 2-month incidence of
diagnosed neovascular depression was 11.6 % in the intervention group
AMD in one eye and and 23.3 % in the control group (OR, 0.39; 95 %
pre-existing AMD in CI, 0.170.92), but the effect diminished by 6
the other eye months
Acute coronary syndrome (ACS)
Hansen et al. 240 patients aged 18 X Intervention: SSRI, Hospital Escitalopram was effective in preventing
[107] and over with ACS escitalopram post-ACS depression. The incidence of ICD-10
Control: placebo depression was 1.6 % in the intervention group
and 8.4 % in the control group (P = 0.022)
Hip fracture
Burns et al. 172 patients aged 60 X Intervention: CBT Hospital The intervention was not effective in preventing
[96] and over with hip Control: usual care depression. The 6-week incidence of depression
fracture, and surgically in the intervention group was 6 %, which was
treated within past 2 not significantly different from 16 % in the
weeks control group (OR, 0.40; 95 % CI, 0.121.30;
P = 0.15)
The intervention column indicates whether the intervention involved a pharmacologic component (Drug) and/or non-pharmacologic component
(Non-drug)
Abbreviations: RR relative risk, OR odds ratio, HR hazard ratio, 95 % CI 95 % confidence Interval, PEARLS the program to encourage active rewarding lives
for seniors (PEARLS), HIV/AIDS human immunodeficiency virus infection/acquired immunodeficiency syndrome, DHEA dehydroepiandrosterone, PST
problem-solving therapy, CBT cognitive behavioral therapy, SNRI serotoninnorepinephrine reuptake inhibitors, SSRI selective serotonin reuptake inhibitors,
NaSSA noradrenergic and specific serotonergic antidepressants, HAM the Hamilton depression scale, HAM-D17 the 17-item subscale of HAM, HAM-D6 the
6-item subscale of HAM, BDI the Beck depression inventory, CGI-S the clinician global impression-severity scale, HADS hospital anxiety and depression scale,
GHQ-28 the general health questionnaire-28, DSM-IV Diagnostic and Statistical Manual of Mental Disorders, 4th edition, ICD-10 international classification
of diseases tenth revision

conditions, and often are accompanied by depression, fewer studies were focused
on prevention among persons with these conditions. The study conducted by Hansen
et al. [107] was the only trial on preventing depression post acute coronary syn-
drome. Other studies focused on cancer [108112], arthritis [113, 114], diabetes
and rheumatologic diseases [115], hip fracture [96], and senile macular degenera-
tion [116].
4.4.3 Nature of the Prevention Interventions Studied
The table provides an indication of whether the prevention intervention for a given
study was primarily pharmacologic (Drug) or non-pharmacologic (Non-drug).
Pharmacologic treatments were primarily selective serotonin reuptake inhibitors
(SSRIs), targeting biological mechanisms for the link between physical illness and
the development of depression (physiological changes discussed above and illus-
trated in Fig. 4.1). Non-pharmacologic interventions were modeled after psycho-
therapy such as problem-solving therapy [103, 116] or cognitive-behavioral therapy
[96, 108, 109, 113]. Other non-pharmacologic interventions included nonspecific
psychological strategies or patient education [108, 111, 114, 115]. All studies for
prevention of depression after stroke employed drug administration, reflecting the
evidence that depression poststroke is associated with biological mechanisms [117,
118]. In contrast, for most other conditions non-pharmacologic management was
applied, interventions that would ameliorate the consequences of physical disorders
or depression (disability, pain, stress, risk behaviors, loneliness, hopelessness) dis-
cussed above. The use of non-pharmacological interventions for prevention of
depression would avoid exposure to medications among persons who do not have
depression. Few studies evaluated an intervention comprising both pharmacologic
and non-pharmacologic management.
4.4.4 Trial Design and Interpretation
Rates of attrition were generally high among included prevention trials, which could
be due to potential adverse drug effects or increased treatment burden related to psy-
chological interventions. Even though some studies reported that attrition was not
differential, the loss of participants may reduce study power and adversely affect the
validity of the study. Stroke, acute coronary syndrome, cancer, and other conditions
impose a variety of treatment burdens on patients so that additional interventions
without direct or immediate clinical effects may not be acceptable [95]. So even with
good participation rates, lack of adherence to the intervention might limit effects.
Studies of stroke provide an example of design and reporting issues for preven-
tion trials.
Quality and design of the studies to prevent depression in stroke varied widely.
For example, some study recruited patients immediately after the stroke [104], some
recruited as far out as 6 months [105] or 3 months [103], and others varied from
2 weeks to 1 month [9395, 106]. Timing of interventions may not be consistent

with when depression might be expected to arise after a stroke. The specified period
for what patients could be included in a study has implications for the introduction
of survival bias. That is, patients have to survive (i.e. be depression free) up to the
time of study enrollment. The difference in this inclusion criterion also implies dif-
ferences in the timing of treatment. Rovner et al. [116] reported their prevention
intervention was more effective 2 months after vision impairment among patients
with age-related macular degeneration than at 6 months. If a prevention window
exists in other medical conditions, different preventive effects might partially be
attributed to the variations in the timing of intervention. Most of the stroke studies
used an antidepressant for prevention; however, how the drug was used varied
widely, and few studies provided evidence for how different doses, frequency of
administration, or changes in dose were determined.
4.5 Opportunities for Prevention of Depression

in Medical Care
The American health care system is undergoing substantial change. The IOM report
Crossing the Quality Chasm: A New Health System for the 21st Century recom-
mended a model consistent with how the most serious causes of disability have
changed over past decades: the need to deal with chronic disease in contrast with a
focus on acute care [119, 120]. The various elements of redesigned practice have
crystallized around the chronic care model (the Wagner model) [121, 122] that
focuses on improvement of chronic care [123]. The Chronic Care Model consists of
six elements: Health Care Organization, Delivery System Design, Decision Support,
Clinical Information Systems, Self-Management, and Community Resources.
Health Care Organization involves the structure, goals, and values of the care pro-
viders organization and its relationships with purchasers, insurers, and other pro-
viders. This is likely to differ across settings. Delivery System Design defines the
structure of medical care such as practice teams where personnel with different
levels of training are responsible for different components of patient care. This com-
ponent may also be different across different treatment settings. Decision Support
describes the standards of care used to make treatment decisions. Clinical
Information Systems includes computerized systems that can serve as reminders to
comply with treatment guidelines, feedback on provider performance, or as patient
registries. Computerized databases such as these are not likely to include patients
with depression or at risk for depression. Self-Management is the education and
support of the patient with a chronic illness to acquire skills and confidence to man-
age their chronic illness through routine assessments of problems and accomplish-
ments. Community Resources include activities that are community-based and may
serve to complement care provider services. A hybrid model that integrates bio-
medical approaches provided in the clinic and informal community approaches may
more effectively improve outcomes over clinical approaches alone with greater
potential for sustainability and impact [124]. The chronic care model is translated
into practice in the patient-centered medical home, currently being implemented
through incentives to improve care. Self-management, decision support, information

systems (including registries that facilitate call back of patients for monitoring), and
other elements of practice redesign outlined here should facilitate putting preven-
tion into practice. Physicians can personalize prevention or treatment strategies by
taking into account patient characteristics and careful attention to how medical con-
ditions and depression are linked.
4.6 Opportunities for Prevention of Depression

in the Community
The Experience Corps (EC) program is a community-based health promotion model

with the purpose of enhancing multiple pathways that link physical and mental
disorders, namely, physical, psychological, social, and cognitive function among
older adults, which is effective in preventing aging-related disability, as well as late-
life depression [125]. Older adults participating in this program volunteer in public
elementary schools to play a meaningful role in supporting childrens education 15 h
per week during the full school year. The causal model is composed of three primary
pathways, including physical activity, cognitive activity, and social activity. The pro-
gram showed that it was effective in increasing participants physical activity in that
the average distance walked, stairs climbed, and kilocalories consumed were signifi-
cantly higher in the intervention group comparing to the control group [126]. A sub-
study examined effects on neurocognitive plasticity using functional magnetic
resonance imaging showing increased activity in prefrontal cortex and improved
executive functions among older adults in the intervention condition [127]. The inter-
vention not only reduced disability and dependence but also increased self-efficacy
in managing daily life and medical conditions. Social activity likely reduced partici-
pants risk for depression through socio-psychological pathways. Being a member of
the volunteer group gave a sense of group identity, engaging in school activities
increased social interaction and reduced social isolation, and sharing wisdom with
school-age children increased sense of life purpose [125]. In summary, the EC model
is a comprehensive intervention for improving older adults overall health, and has
great implications for preventing late-life depression. Given the nature of the program,
medically ill older adults with severe illness may not be able to participate in such
programs that require relatively intact mobility and cognitive functions. Nevertheless,
Experience Corps illustrates the different prevention strategies that could be designed
for community settings to address multiple pathways.
4.7 The Future of Prevention in Medical Conditions
Examining the etiology of both depression and physical disorders and evaluating
medical patients overall risk for depression are important for future prevention trial
design. As we discussed above (Fig. 4.1), the development of a physical disorder is
attributed to a series of biological, social, psychological, and behavioral risk factors,
which may simultaneously elevate individuals risk for depression. For example,
Hemingway and Marmot [128] summarized psychosocial factors associated with

coronary heart disease in a systematic review, where low social support was demon-
strated to be an independent etiological factor for coronary heart disease. In con-
trast, adequate perceived social support is a well-known stress-buffer against
depression [129]. Interventions targeting on these factors can not only control for
physical disorders, but also prevent the occurrence of depression. Medical patients
risk for depression may differ by their predisposition factors and severity of physi-
cal disorders, which potentially affect the prevention effects. Therefore, individuals
shared etiological and prognostic factors for physical disorders and depression, as
well as their overall risk levels for depression should be comprehensively evaluated
at trial enrollment, and accounted for in data analysis. This would also make it pos-
sible to compare results across studies.
Although the bidirectional relationship between physical disorders and depres-
sion has been well known, there are still relatively few randomized controlled trials
on preventing depression among medically ill patients. Even though there were
variations and limitations in sample selection, intervention strategies, and study
designs, existing studies provided great insights on reducing physical and mental
comorbidity. Both pharmacological interventions and non-pharmacological inter-
ventions have the potential to prevent depression among patients with physical dis-
orders. More studies should be conducted to investigate the efficacy, effectiveness,
and cost-effectiveness of preventive interventions, and how such interventions can
be incorporated into practice.
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Vascular Depression and the Role
of Neuroimaging and Biomarkers 5
Sara L. Weisenbach, Nicolette M. Gabel,
and Emily M. Briceo
Abstract
The relationships between cerebrovascular risk factors, executive dysfunction, and
depression during late life have been well established by behavioral and neuroim-
aging studies. In this chapter, we begin with a description of how vascular depres-
sion is conceptualized. We then discuss evidence from structural and functional
neuroimaging literature that supports the vascular depression hypothesis. We go on
to review neuropsychological investigations from the field of neuropsychology that
suggest cognitive features associated with late-life depression, more broadly,
and vascular depression specifically. Next, potential mechanisms underlying the
relationship between depression and interruption to vascular integrity are identi-
fied. In conclusion, we provide an overview of treatment strategies and prediction
of treatment response in the context of vascular depression.
Keywords
Vascular depression Late-life depression Cognition Neuroimaging
Disconnection Inflammation Hypoperfusion Genetics Intervention
S.L. Weisenbach, Ph.D. (*)

Department of Psychiatry, University of Illinois at Chicago, Chicago, IL USA
Research and Development, Jesse Brown VA Medical Center,
1747 West Roosevelt Road, Suite 155, Chicago, IL 60607, USA
e-mail: sweisenbach@psych.uic.edu
N.M. Gabel, Ph.D. E.M. Briceo, Ph.D.
Department of Physical Medicine and Rehabilitation, University of Michigan
Medical School, Ann Arbor, MI, USA

58 S.L. Weisenbach et al.
5.1 Introduction
Late-life depression (LLD) is a heterogeneous disease, with multiple risk factors,

etiologies, and clinical features. It has been recognized for many years that there is a
significant relationship between the presence of depression and cerebrovascular dis-
ease in older adults [1, 2]. This subtype of LLD was eventually termed vascular
depression. The vascular depression hypothesis states that cerebrovascular disease
may predispose, precipitate, or perpetuate some geriatric depressive syndromes
([3], p. 915). It is supplemented by two propositions as to the defining features and
characteristics of vascular depression. The first, proposed by Alexopoulos and col-
leagues [3, 4] suggests that individuals with depression and vascular risk factors,
such as hypertension, atherosclerosis, and/or history of transient ischemic attacks or
surgery for vascular disease have symptoms that are similar to what might be antici-
pated from lesions to striato-pallido-thalamo-cortical pathways, including cognitive
deficits, psychomotor retardation, poor insight, and functional disability. Subsequent
work by this group has focused more broadly on the co-occurrence of depression and
executive dysfunction, with associated occurrence of psychomotor retardation, loss
of interest in activities, and mild paranoia [5, 6]. The second proposal by Krishnan
and colleagues defines vascular depression on the basis of MRI findings of subcorti-
cal ischemic lesions [7, 8], with associated features including older age, lassitude,
history of hypertension, and negative associations with family history of mental ill-
ness, and loss of libido [8].
This chapter reviews the literature on LLD that is linked to features associated
with cerebrovascular risk and disease. We begin with a discussion of evidence from
structural and functional neuroimaging that examines the vascular depression
hypothesis. We then go on to review work from the field of neuropsychology that
suggests cognitive features associated with LLD, more broadly, and vascular depres-
sion specifically. This is followed by a discussion of potential mechanisms underly-
ing the relationship between depression and vascular function. We then provide an
overview of treatment strategies and prediction of treatment response in the context
of vascular depression.
5.2 Morphological Studies Supporting the Vascular

Depression Hypothesis
5.2.1 White Matter Lesions
There have been a multitude of studies associating white matter abnormalities with
depression in older adults using MRI technology to visualize lesions, or what appear
as hyperintensities in the white matter on T2-weighted scans. A systematic review
concluded that white matter hyperintensities (WMH) are more common and severe
among older adults with depression compared to their non-depressed peers [9]. The
etiology of these lesions can represent a variety of pathologies including ischemia,
5 Vascular Depression and the Role of Neuroimaging and Biomarkers 59
perivascular demyelination, arteriosclerosis, gliosis, or partial loss of myelin and

axons [1012]. WMHs are associated with older age [13] and cerebrovascular risk
factors, including diabetes, heart disease, and hypertension [1417].
White matter severity and extent of WMH volume has been related to the sever-
ity of depression in late life [18, 19]. For example, among 639 older, community-
dwelling adults, white matter lesion (WML) severity was found to predict depressive
episodes and symptoms over a 3-year period [19]. While those with first onset of
depression in late life tend to exhibit greater severity of WMH [20, 21], individuals
with first onset of depression earlier in life are also at greater risk of vascular disease
and stroke relative to the normal population [22]. WMH severity has also been asso-
ciated with greater cognitive deficits, particularly in the domains of executive func-
tioning and memory [2325]. It is notable that in these studies, WMH were not as
strongly associated with cognitive deficits in the non-depressed group, suggesting
an interaction between depression and white matter pathology developing into more
severe executive dysfunction among older patients.
The location of WMH may be relevant in the association of LLD with WMH
severity, with a number of studies localizing WMH in depression to frontal regions
[2628] and in specific white matter tracts that are functionally associated with
cognitive and emotional functioning, including the cingulum bundle, uncinate fas-
ciculus, and superior longitudinal fasciculus [25, 29, 30]. There has been some
investigation in the field as to the functional significance of periventricular versus
deep WMH. The European multicenter study (LADIS) found that after controlling
for cognitive impairment, there was a stronger association between deep white mat-
ter lesions and depressive symptoms compared to lesions in periventricular areas
[31]. It is notable that periventricular WMH are thought to be non-vascular in ori-
gin, relating to disruption of the ependymal lining, whereas the majority of deep
subcortical WMH are associated with incomplete ischemic destruction or widened
perivascular spaces without considerable ischemic tissue damage [32]. At the same
time, WMH across regions are strongly related [33] suggesting that distinguishing
between WMH in these regions may be capricious and part of a larger cardiovascular
disease picture.
5.2.2 White Matter Tracts
Another way of investigating white matter integrity is with diffusion tensor imaging
(DTI), which measures the diffusion of water in tissues and allows for indirect evi-
dence of the microstructure of white matter, most commonly represented as frac-
tional anisotropy (FA) and mean diffusivity (MD). DTI may be more sensitive to
white matter pathology than is quantification of WMH, as Sexton and colleagues
[34] found no differences in WMH volume, but detected differences in FA between
depressed and non-depressed groups, though WMH severity is associated with FA
in LLD [35]. A number of studies have found lower FA in widespread regions
among individuals with LLD relative to controls [34, 36, 37]. For example, Sexton and
colleagues [34] found that 36 % of voxels (using a mean FA skeleton representing
the centers of all tracts that were common to all participants) were decreased in
individuals with remitted depression (n = 36), relative to controls (n = 25) at p < 0.05
and 16 % at p < 0.01, and there were no areas in which FA was higher in the LLD
group. Further, lower FA has been associated with poorer performance on measures
of cognitive functioning among patients with LLD [35, 3840] and with measures
of cerebrovascular risk severity. In a group of LLD patients, those with a higher
score on the Framingham Stroke Risk Profile scale demonstrated lower FA across a
number of white matter regions, while this association was detected only in the
body of the corpus callosum among non-depressed controls [41]. It is important to
recognize that FA reflects the organization of fiber tracts, including fiber density,
axonal diameter, or myelination in white matter. Thus, lower FA can result from
multiple pathophysiological sources [42, 43].
Magnetic transfer resonance (MTR) imaging is another neuroimaging technique
that can be used to assess white matter integrity, but is specifically sensitive to myelin,
and to a lesser extent, axonal integrity. MTR provides information about the macro-
molecular structure of the cerebral white matter based on the interplay between the
normally observed tissue water signal with protons contained in the large macromol-
ecules, and is expressed as a ratio of free water (unbound to protons) to magnetization
of the bound protons (including myelin; [44, 45]). In an early study using MTR to
investigate patients with LLD, Kumar and colleagues [46] found lower MTRs in the
genu and splenium of the corpus callosum, right caudate nucleus, putamen, and occip-
ital white matter in eight LLD patients relative to eight non-depressed controls. In a
larger study, Gunning-Dixon and colleagues [47] found lower MTR in a number of
left frontostriatal and limbic regions, as well as thalamus, splenium of the corpus
callosum, inferior parietal, precuneus, and middle occipital white matter regions in
55 older depressed patients relative to 24 non-depressed controls.
Together, the aforementioned studies provide support for the vascular depression
hypothesis. They demonstrate that white matter integrity is reduced in patients with
LLD relative to controls, is somewhat specific to regions important for cognitive
and emotional functioning, and is associated with cognitive functioning and depres-
sion severity.
5.3 Functional Neuroimaging Studies Supporting

the Vascular Depression Hypothesis
5.3.1 Task-Related Functional Magnetic Resonance

Imaging (fMRI)
Given hypotheses regarding disruption of frontostriatal pathways in LLD, the

majority of task-related functional neuroimaging studies to date have utilized
executive functioning tasks to manipulate frontalstriatal circuitry. These studies have
converged to reveal disruption in the prefrontal and striatal systems that support
executive functioning. Although some studies have reported reduced activity of the
dorsolateral prefrontal cortex (DLPFC; [48]) and anterior cingulate [49], another
study [50] reported hyperactivation in depressed elders in several frontal (e.g., anterior
cingulate, orbitofrontal, superior frontal gyrus) and insular regions. In addition, evi-
dence for reduced hippocampus [49] and increased basal ganglia activation [48, 50]
have been reported during executive functioning tasks. Although several factors
may affect the extent and direction of activation of disrupted executive control cir-
cuitry, findings by one group [51] suggest that the presence of comorbid anxiety
may be related to hyperactivation of this network. Specifically, this group reported
that older depressed adults with comorbid anxiety exhibited greater and more sus-
tained activation than older depressed adults without comorbid anxiety in regions
pertinent to executive functioning (e.g., dorsal anterior cingulate, supplementary
motor area, posterior cingulate) during a cognitive control task.
Recent work has also revealed disrupted functioning of networks related to emo-
tional control. For example, Brassen and colleagues [52] reported reduced activa-
tion of the ventromedial prefrontal cortex in response to viewing negative emotional
words, a pattern that was associated with greater symptom severity. Aizenstein and
colleagues [53] reported greater activation of the subgenual anterior cingulate gyrus
(sgACG) in a sample of depressed elders compared to healthy comparison elders.
In the depressed group, greater activity of the sgACG was associated with greater
white matter pathology, suggesting that reduced integrity of white matter in prefron-
tallimbic pathways may interfere with the capacity for prefrontal systems to modu-
late hyperactive limbic regions.
Taken together, the circuitry supporting cognitive and emotional control appears
to be disrupted in geriatric depression. With the exception of one [48], all of the
aforementioned studies reported equivalent performance between the depressed and
healthy comparison groups, suggesting that compensatory mechanisms occur in
adults with LLD to maintain overall performance. It also suggests that functional
imaging findings are more closely related to underlying brain pathology than are
behavioral measures. A limitation to having equivalent performance between
groups, however, is that it remains unclear how these circuits are engaged under
conditions in which their resources are taxed beyond their capacity (i.e., at a point
when performance becomes disrupted relative to controls), which could provide
useful information regarding the plasticity of neural mechanisms in the context of
disrupted circuitry, underlying the often-observed relative deficits in executive func-
tioning and memory in LLD.
5.3.2 Resting state fMRI
Resting state fMRI studies have provided further evidence for the hypothesis that
LLD is associated with disrupted connectivity between brain regions important for
modulating emotion processing. Resting state functional connectivity analyses
evaluate the temporal relationships between activation among different brain regions.
In the geriatric depression literature, most studies to date have identified a seed
region (i.e., a region of theoretical empirical interest) and measured associations
between activation in that region and another seed region, or all other areas in the
brain, in order to determine the functional synchrony between cerebral structures in

a network. Disrupted connectivity between regions could be a result of abnormal
functioning of one or both regions, or due to aberrant structural pathways between
these areas. Resting state fMRI studies often target the default-mode network, a set
of regions that are engaged during rest and inhibited during task performance [54].
Critical nodes of the default mode network include medial prefrontal cortex, poste-
rior cingulate, precuneus, and lateral inferior parietal cortex. The posterior cingulate
cortex, in particular, is often used as a seed region for resting-state analyses because
of its participation in default-mode networks, direct connections with the hippo-
campal formation [55] and associations with Mild Cognitive Impairment (MCI), a
precursor to dementia [56].
A number of studies are accruing to indicate disruption of the default-mode net-
work at rest in LLD. For example, Wang et al. [57] found lower connectivity
between posterior cingulate cortex and several right frontal regions (i.e., superior,
middle, and inferior frontal gyri) and higher connectivity in left inferior temporal
and fusiform gyrus in a sample of adults with remitted LLD compared to healthy
comparison adults. Wu and colleagues [58] reported reduced connectivity between
the posterior cingulate and the sgACG, and increased connectivity in the dorsome-
dial prefrontal and orbitofrontal cortices. These authors found an inverse relation-
ship between WMH volume and resting state connectivity in medial frontal gyrus,
suggesting that disrupted white matter integrity contributed to disrupted connectivity
between these regions.
Altered connectivity of striatal and limbic pathways has also been associated with
depression in older adults. Increased connectivity between the caudate and a number of
frontal and subcortical regions has been reported [59]. In older adults with MCI,
increased symptoms of depression were associated with greater connectivity between
amygdala and DLPFC [60] and hippocampus with regions in the default-mode net-
work (i.e., medial prefrontal cortex, middle temporal gyrus, posterior cingulate; [61]).
Taken together, these studies demonstrate altered connectivity in a number of circuits
pertinent to cognitive and affective control, which may be driven by poor integrity of
structural connections or dysfunction of individual regions within these networks.
Whereas the above described functional connectivity analyses are considered a
model-driven approach in which a seed region is selected for theoretical purposes,
data-driven approaches (e.g., regional homogeneity; ReHo) analyze resting state
activation data with regard to the temporal relationship between spatially neighbor-
ing regions. Abnormality in ReHo is assumed to be reflective of either increased or
decreased regional activity during rest. Identification of areas of disrupted regional
neural activity at rest may aid in generation of hypotheses regarding abnormally
functioning regions in geriatric depression. Studies have identified abnormal ReHo
in a number of cortical and subcortical regions in adults with geriatric depression.
Altered ReHo, both increased and reduced, has been reported in a number of pre-
frontal (i.e., [62, 63]), temporal and parietal [6264], insula [63], basal ganglia [62],
and cerebellum [64] foci. Abnormal ReHo has also been demonstrated in those with
remitted geriatric depression [65]; in this sample, altered ReHo in the right putamen
and left superior frontal gyrus was related to slowed psychomotor processing speed
and executive functioning.
5.3.3 Positron Emission Tomography (PET)
PET has been used to generate and test hypotheses regarding direct neural mechanisms
underlying the geriatric depression syndrome. While the studies described below
provide less direct support for the vascular depression hypothesis than structural
and functional MRI studies, they contribute to broadly characterizing the geriatric
depressive syndrome. We review them as part of this chapter because the mecha-
nisms studied may be relevant to vascular functioning when considered within a
broader context.
Given the increased risk for Alzheimers disease in depressed elders (e.g.,
[66]), a few studies have utilized PET techniques to investigate the connection
between LLD and pathology linked to Alzheimers disease. Butters et al. [67]
investigated -amyloid deposition with Pittsburg-compound B (PiB) in a small
sample of older adults with remitted depression; a majority of these individuals
met criteria for MCI. PiB imaging showed that approximately one half of these
individuals had PiB retention consistent with -amyloid accumulation character-
istic of early Alzheimers disease. Lavretsky et al. [68] utilized FDDNP-PET
(FDDNP; a molecule that binds to amyloid plaques and neurofibrillary tangles) to
investigate Alzheimers pathology in a sample consisting of approximately half
elders with MCI and the other half cognitively normal. In those with MCI, greater
depression scores were related to lateral temporal FDDNP binding, and greater
anxiety scores were associated with greater posterior cingulate FDDNP binding.
In the healthy comparison group, greater depression symptoms were related to
FDDNP medial temporal binding, and greater anxiety with medial temporal and
frontal FDDNP binding. Taken together, these studies provide preliminary evi-
dence suggesting an interaction between symptoms of Alzheimers pathology and
symptoms of depression and anxiety, which may also depend on the presence of
cognitive symptoms.
PET studies have also recently investigated the functioning of the serotonergic
system in older adults with depression, due to the primary function of antidepres-
sant medication affecting the serotonergic system. Diminished serotonergic recep-
tor binding has been reported in older adults with depression in the raphe nucleus
([69]; 5HT1a) and hippocampus ([70]; 5HT2a). Two studies [71, 72] have reported
a blunted right cortical response to acute citalopram treatment, a serotonin reuptake
blocker, compared to healthy comparison elders with possible compensatory metab-
olism in left hemisphere. Smith and colleagues [73, 74] also reported that in a small
sample, clinical doses of citalopram occupied over 70 % of the serotonin transporter
receptors in the striatum and thalamus, in addition to a number of cortical and lim-
bic regions (e.g., anterior cingulate, middle frontal and middle temporal, parahip-
pocampal gyrus), and that in some of these regions glucose metabolism also
decreased from before to after treatment. The authors concluded that high receptor
occupancy by SSRIs is associated with reductions in glucose metabolism in geriat-
ric depression. Taken together, these data indicate altered functioning of the seroto-
nergic system in geriatric depression that may improve with effective pharmacological
treatment.
5.4 Cognition in the Context of Vascular Depression
Cognitive changes associated with depression have been the focus of research for
decades. Results have been inconsistent, likely as a result of methodological differences
in how depression is diagnosed and cognitive functioning measured, as well as the
effects of potential subtypes and the severity of depression (for a review, see [75]),
though deficits in executive functioning, learning and memory, and attention have been
associated with depression in most studies [75]. In older adults, additional confounding
factors include the potential presence of primary degenerative disorders, such as
Alzheimers disease, which can pose a challenge to differential diagnosis in its early
stages. Differences in the pattern of deficits exhibited on neuropsychological assessment
have been found to distinguish between depression with cognitive impairment and
dementia (for a review, see [76, 77]), namely mild-to-moderate deficits in memory
encoding, processing speed, and attention in the former versus the addition of more
pervasive impairments involving language and motor functioning in the latter.
5.4.1 Cognition and White Matter Disruption
The relationship between WMH and cognitive functioning in vascular depression

has not been consistently demonstrated. With the advent of diffusion tensor imaging
(DTI), however, which can measure more subtle white matter pathology, the level of
disruption in white matter tracts has again become a variable of interest, with stud-
ies demonstrating significant correlations between severity of white matter disrup-
tion, depression, and neuropsychological performance [35, 39, 40]. In particular,
executive functioning and processing speed have been shown to be significantly
negatively correlated with disruptions in white matter integrity in the frontalstria-
tallimbic system [39, 40], whereas working memory and episodic memory were
less strongly related [39]. In an earlier study by Lesser and colleagues [78], older
adult participants with late-onset LLD (i.e., after age 50) and early-onset LLD (i.e.,
before age 35) were compared with non-depressed controls on tests of neuropsy-
chological function and WMH burden on MRI. They found that depressed partici-
pants performed more poorly than controls on tests of construction, nonverbal visual
memory, nonverbal intelligence, information processing speed, and executive func-
tion (specifically, verbal phonemic fluency). Late-onset LLD was associated with a
greater burden of WMH than early-onset LLD, and within the late-onset group,
greater WMH burden was significantly associated with poorer executive function.
WMH burden was not associated with severity of depression.
5.4.2 Executive Functioning
Though the aforementioned study did not report whether depression severity was
associated with executive functioning, this association has since been demonstrated.
Baudic and colleagues [79] compared the performances of depressed and non-depressed
older adults on tests of verbal recall memory, working memory, and executive
functioning. Executive functioning domains included reasoning, estimation,
response inhibition, verbal fluency, selective attention, set-switching, problem-
solving, and perseveration. As expected, depressed participants performed more
poorly than non-depressed participants in the domain of verbal memory and on each
of the executive functioning tests except one, which was considered the most highly
structured and least demanding. A significant relationship was found between
depression severity and performance on several of the executive functioning tests,
with more severely depressed participants performing worse.
In an effort to better characterize the specific executive dysfunctions associated
with LLD (vs. those associated with depression across the lifespan and with healthy
aging), Lockwood et al. [80] compared 20 younger (i.e., ages 2060) and 20 older
(i.e., ages 61+) depressed participants with 40 age-matched non-depressed controls on
a variety of measures of executive functioning. Domains assessed included sustained
attention (i.e., attention functioning over time), selective attention (i.e., response
inhibition and vigilance), focused effort (i.e., mental manipulation, processing speed,
and effortful information processing), and inhibitory control (i.e., perseveration and
commission errors). A significant age by depression interaction was found in the
domains of focused effort and inhibitory control, with older depressed patients dem-
onstrating longer response latencies, more perseverative responses, slower processing
speed, and more difficulty set-shifting than non-depressed older participants and
depressed and non-depressed younger participants.
5.4.3 Memory
Results of research examining the relationship between LLD and memory function-
ing have been mixed. From a lifespan perspective, a meta-analysis of 147 studies
exploring the association of memory impairments with depression across age groups
demonstrated that the relationship is stronger in younger depressed patients than in
older depressed patients [81]. It is likely the case that memory processes recruit the
not only medial temporal regions, but also the engagement of parietal association
and frontal cortex in older adults (and especially depressed older adults) to a greater
extent than in younger adults. As mentioned above, Baudic and colleagues [79]
assessed memory and executive functioning in depressed and non-depressed par-
ticipants and found that the former performed worse than the latter in both domains
of cognitive functioning. They also found that verbal memory was significantly
associated with executive functioning in the depressed, but not in the non-depressed,
participants. The findings of Elderkin-Thompson et al. [82] also support this tenant.
Measures sensitive to different aspects of memory were used to examine patterns of
deficits in recall, retention, and recognition of explicit and implicit material in
community-dwelling elderly participants with moderately severe depression
(n = 112) and non-depressed (n = 138) controls. Implicit learning was assessed
through a test of the participants ability to develop predictions based on probabilis-
tic patterns presented through abstract visual stimuli, while explicit learning was
assessed using word-list (verbal memory) and complex figure (visual memory)
learning tasks, with recall and recognition trials. Additionally, measures of attention,
processing speed, language fluency, divided attention, response inhibition, and
abstract conceptualization were administered. Depressed participants performed
more poorly, as expected, on standard measures of executive functioning and pro-
cessing speed. They were also found to demonstrate greater inefficiency learning
the word list on the verbal memory test compared to non-depressed controls, yet the
percentage of words learned that were later recalled after a delay was the same.
In other words, what was learned was retained, but the act of learning involves the
use of working memory to categorize and organize material for encoding, and is
therefore mediated by executive functioning processes that appear to be compro-
mised in depressed older adults. Implicit memory was not found to be significantly
different between depressed and non-depressed participants.
5.4.4 Processing Speed
Processing speed is one of the most important determinants of cognitive functioning,

and a decrement in processing speed with advancing age has been proposed as the main
determinant of age-related cognitive decline (for a review, see [83]). In a study compar-
ing depressed older adults to non-depressed controls, Butters and colleagues [84]
demonstrated that variance in processing speed strongly predicted performance on all
other cognitive domains studied (i.e., executive functioning, language, visuospatial
functioning, and memory), and mediated the relationships between age and cognitive
performance, and between depression severity and cognitive performance. Additionally,
ventricular volume on MRI was found to be associated with age and performance in the
domain of language. This study found no relationships between WMH burden on
MRI and cognitive performance or depression severity. A similar study by Sheline
and colleagues [85] demonstrated that processing speed performance mediated the
relationships between cognitive performance and several risk factors, including vas-
cular burden and depression severity. Vascular burden in this study was defined using
a stroke risk prediction assessment that incorporates demographic variables, systolic
blood pressure, and the presence of chronic illness and cardiovascular risks.
5.4.5 LLD and Risk of Dementia
LLD with cognitive dysfunction has been shown to result in greater disability than
depressive symptoms alone [6], and MCI with co-occurring LLD has been shown to
double the risk of developing Alzheimers disease (AD) compared to MCI alone [86].
The conversion from MCI to AD also appears to occur earlier in patients with co-
occurring depressive symptoms, as demonstrated by Modrego & Ferrandez [86] in
their prospective cohort study of 114 outpatients diagnosed with amnestic MCI.
A cross-sectional study by Gualtieri and Johnson [87] similarly demonstrated greater
general cognitive decline in depressed older adults compared to non-depressed older
adults, first apparent at ages 5564, and worsening precipitously thereafter.
5.5 State Versus Scar Effects in LLD
Given accruing evidence for abnormal functioning of a number of cortical and

subcortical networks in geriatric depression, of particular interest is whether these
abnormalities are a reflection of the actively depressed state, or whether they may
persist following successful resolution of symptoms. To date, studies have investi-
gated this question through either longitudinal investigation of adults with geriatric
depression, or comparison of depressed elders who are actively depressed versus
those who have achieved symptom remission. Of encouragement, successful treat-
ment has been reliably associated with normalization of some aspects of disrupted
network functioning. For example, successful antidepressant treatment is associated
with reduction of the elevated cerebral glucose metabolism observed during
depressed states (e.g., [7174]), with greater symptom reduction associated with
greater metabolic change (e.g., [88, 89]). In a task-related fMRI study, Brassen et al.
[52] reported that the reduced engagement of the ventromedial prefrontal cortex that
was measured during viewing of emotional words resolved following a successful
trial of antidepressants. Aizenstein et al. [90] reported amelioration of the reduced
DLPFC and dorsal anterior cingulate cortex activation during a cognitive control
task, following successful treatment. However, disruption in the connectivity
between these regions did not improve with treatment, suggesting that disrupted
functional synchrony between these cognitive-control regions may be a phenome-
non that persists following remission. Supporting the hypothesis of persisting dis-
rupted functional connectivity, Wu et al. [58] reported that resting state functional
connectivity of the posterior cingulate with the sgACG and dorsomedial prefrontal
cortex, although improved following successful antidepressant treatment, was still
reduced compared to healthy comparison elders.
In addition to evidence for persistence of disrupted functional connectivity, a
few studies have reported persisting disruption of prefrontal circuitry following
symptom remission. For example, Wang et al. [91] reported reduced activation in
older adults with both active state and remitted LLD compared to never-depressed
subjects in a number of anterior and posterior cortical regions, including the left
anterior cingulate gyrus, the anterior portion of the posterior cingulate, and the
left angular gyrus, several foci of which fall along a prominent white matter tract
(i.e., the superior longitudinal fasciculus). Alexopoulos et al. [92] reported that
among older adults who did not successfully respond to antidepressant treatment,
event-related potentials revealed abnormal functioning of the rostral anterior cin-
gulate gyrus during an executive functioning task. Yuan et al. [65] reported that
altered regional homogeneity of right putamen and left superior frontal gyrus in a
remitted geriatric depression sample was connected to slowed psychomotor pro-
cessing speed and executive functioning. Taken together, these studies suggest
that although a subset of the functional abnormalities observed during the LLD
state may resolve with successful treatment, other abnormalities persist and may
be tied to damage to the structural connectivity in important affective and cognitive
networks.
5.6 Physiological Changes Underlying the Relationship

Between Vascular Disease and Depression
While there is now enough evidence to conclude that in at least a subset of older
individuals there is a clear relationship between vascular pathology and depression,
it is not yet completely apparent why this relationship exists. While space limita-
tions prohibit a complete discussion of all possible mechanisms, we present a few
candidate hypotheses below that have been proposed in a recent manuscript by
Taylor and colleagues [30].
5.6.1 Disconnection
When vasculature that serves cerebral areas important for cognition and affective
functioning is compromised, it can disrupt neural connections in and between these
regions and impact behavior. As reviewed above, there is evidence that when spe-
cific fiber tracts and neural circuits are damaged, there are direct relationships with
cognitive performance and affective dysregulation (see [93]). For example, a recent
study by Lamar and colleagues [38] found that lower FA in the uncinate fasciculus
predicted poorer performance on a measure of executive functioning among 26
patients with LLD. In a study of 145 healthy and cognitively impaired older adults,
Smith and colleagues [73, 74] measured global and focal WMH volume, and found
that WMH in specific regions were associated with impairment in specific cognitive
domains. Specifically, WMH in bilateral temporal-occipital, right parietal periven-
tricular, and left anterior limb of the internal capsule were associated with episodic
memory performance, while WMH in bilateral inferior frontal, bilateral temporal-
occipital, right parietal periventricular, and bilateral anterior limb of the internal
capsule were predictive of executive function performance, independent of total
white matter volume. Finally, Dalby and colleagues [94] demonstrated a positive
relationship between depression severity and fiber tracts intersected by white matter
lesions in the left superior longitudinal fasciculus and the right uncinate fasciculus
among 22 patients with LLD.
5.6.2 Hypoperfusion
Another potential mechanism to account for the relationship between vascular

pathology and depression is reduced perfusion of blood to key brain regions integral
to affective and cognitive processing. There is a growing body of research pertain-
ing to cerebral hemodynamics in the context of LLD. One such measure is that of
carotid intima-media thickness (IMT). The carotid intima-media encompasses the
innermost two layers of the arterial wall is a reflection of atherosclerosis and vascu-
lar disease risk [95], and correlates strongly with atherosclerosis itself [96]. Studies
have shown IMT to be higher among older adults with LLD relative to controls, and
to correlate with WMH among patients with LLD [97]. IMT is also associated with
later of age depression onset [72]. Further, individuals who do not respond to anti-
depressant monotherapy have been shown to have particularly high IMT, relative to
responders and control participants [21, 98].
Arterial endothelial function is another way to assess vascular function and
pathology. Vascular endothelium is the thin layer of cells that line the inner surface
of blood vessels and forms an interface between blood and the rest of the vessel
wall. Endothelial cells are involved in a multitude of functions, including control-
ling the passage of materials and white blood cells in and out of the bloodstream,
blood clotting, inflammation, angiogenesis, fluid filtration, and the control of blood
pressure [99]. While it is not possible to directly assess the functioning of endothe-
lia within the brain, conditions such as diabetes and hypertension that incline toward
endothelial dysfunction typically affect multiple vascular beds [100], often mea-
sured in gluteal fat. Studies of older depressed patients have found reduction in the
vasodilating response to acetylcholine in preconstricted small arteries [101, 102],
though this did not correlate with the severity or volume of WMH [102]. As Taylor
and colleagues [30] proposed, this latter finding suggests that WMH may actually
be an endpoint to perfusion deficits, which do not need to cause ischemia to impact
brain functioning. A study of older patients with LLD found that endothelial func-
tion was poorer in the depressed group relative to controls, and that this was true for
both responders and non-responders to antidepressant monotherapy [21, 98]. Blood
flow velocity using cerebral transcranial Doppler ultrasound is also capable of
reflecting vascular function. Cerebral blood flow velocity increases during mental
activity, while vasomotor reactivity is compensatory for maintaining cerebral blood
flow in the arterioles. A sample of 1,494 older adults who screened negative for
depression at baseline was drawn from the Rotterdam study. Lower peak-systolic,
end-diastolic, and average blood flow velocities were associated with higher depres-
sion symptom severity at the follow-up visit approximately 36 years following the
baseline visit. Mean blood flow velocity and decreased baseline vasomotor reactiv-
ity predicted incident depressive symptoms during the span of the follow-up period
[103]. Another study, also drawing from the Rotterdam sample, found that depres-
sive symptomatology was negatively associated with blood flow velocity and vaso-
motor reactivity, and those diagnosed with a DSM-IV depressive disorder had the
lowest levels of blood flow velocity [104].
5.6.3 Inflammatory Processes
Alexopoulos and Morimoto [105] suggest that inflammatory processes related to

aging and disease may induce neural and/or metabolic changes that predispose to
depression in late life. A number of studies have demonstrated an association
between plasma levels of peripheral pro-inflammatory cytokines and depressive
symptoms in older adults [106115]. Interleukin-6 (IL-6) has most consistently
been associated with depressive symptoms after variables such as age, chronic dis-
ease, cognitive functioning, and antidepressants have been controlled. Perhaps most
relevant to vascular depression specifically, higher levels of IL-6 and C-reactive

protein have been associated with greater white matter pathology [116119].
Pro-inflammatory cytokines impact neurotransmitter systems that are relevant to
depression, including monoamine neurotransmitter pathways [120122], resulting
in reduced tryptophan and serotonin synthesis [120, 123]. They also disrupt func-
tion of glucocorticoid receptors and decrease hippocampal neurotrophic support
[124]. As supported by these and other studies, Alexopoulos and Morimoto [105]
propose that dramatic and prolonged CNS immune response can impact emotional
and cognitive network functions that are relevant to depression and can contribute
to the etiology of at least some LLD syndromes.
5.7 The Role of Genetics in Conferring Risk for Vascular

Depression
First onset of depression in late in life is much less associated with family history of
depression than is onset of depression in earlier life [125]. This does not, however,
preclude genetic or epigenetic factors conferring greater risk of depression onset in
late life. There has been a great deal of work into the role of the serotonin trans-
porter polymorphism, 5-HTTLPR in risk of depression onset early in life. While
there has been no direct association demonstrated between 5-HTTLPR and late-
onset depression, there are findings suggesting environment by gene interactions.
Specifically, having the S/S allele together with pre-existing medical illnesses,
including coronary artery disease [126], cardiac events [127], and stroke [128, 129]
increases risk for developing depression late in life. There has also been work on the
role of brain-derived neurotrophic factor (BDNF) in LLD. Alexopoulos and col-
leagues [130] found that older patients with depression who carried the met allele of
the Val66Met polymorphism were more likely to achieve remission following 12
weeks of treatment with escitalopram than were those homozygous for the val
allele. White matter abnormalities, as measured by DTI, were also predictive of
non-remission, although there was no interaction of white matter abnormalities with
BDNF polymorphism. In a different study, met allele carriers were shown to have
an earlier age of depression onset and lower right hippocampal volume than val/val
carriers, suggesting a neuroprotective role of the val/val genotype [131]. Indeed,
older adults with depression, relative to non-depressed controls are more likely to
carry the met allele of the Met66Val polymorphism [132], and showed greater
WMH burden, regardless of depression status [133].
There is also growing interest into the role of genetic variants associated with
cerebrovascular risk in the context of LLD. Taylor and colleagues have published on
the role of genetic markers associated with the functioning of the reninangiotensin
system (RAS; [134136]). The RAS is involved in the regulation of fluids and blood
pressure, and has also been shown to be involved in physiological and psychosocial
responses to stress, the occurrence of ischemic events, and inflammatory processes
[137]. In their first published study, Taylor and colleagues [134] assessed the
relationship between WML and genes coding for angiotensin-II AT1 receptors
(AGTR1 and AGTR2). They found that depressed and non-depressed men who
were homozygous for the AGTR1 1166A allele had less change in volume of WML
over a 2-year period relative to 1166C allele carriers. Further, men with the AGTR2
C3123A polymorphism and hypertension had less change in WML over the 2-year
period than men without hypertension and men with the A allele. In their second
published study, Taylor and colleagues [134] found variations (using a haplotype-
tagging single nucleotide polymorphism (htSNP) analysis) in the gene coding for
AGTR1 between a large group of older depressed patients and controls. There were
also findings of variation in this gene predicting smaller DLPFC and larger right
hippocampal volumes in the entire sample. A third study [136] showed that, among
depressed older adults, AGTR1 C1166 carriers had greater lesion ratios across a
number of white matter tracts, including the anterior thalamic radiation and inferior
fronto-occipital fasciculus. Finally, Hou and colleagues [138] genotyped
angiotensin-converting enzyme (ACE) insertion/deletion polymorphism in patients
with remitted geriatric depression. They found that D-allele carriers had smaller
white matter volumes in right superior frontal and anterior cingulate gyri and larger
volumes of left middle temporal and right middle occipital gyri relative to I homo-
zygotes. Among D-allele carriers, lower right anterior cingulate volume was nega-
tively associated with performance on the Clock Drawing Test. From these studies,
we can conclude that variations in genes impacting the RAS play a role in vascular
risk and cerebral structural morphology, both within and outside of the context of
depression. Further studies into genetic variations in RAS in LLD may assist in
better elucidating the neurobiology of vascular depression and in predicting course
of illness over time.
5.8 Treatment Strategies
A review of the literature on evidence-based treatments for LLD found that about
50 % of patients improved on antidepressants, but that the number needed to treat
(NNT) was quite high (NNT = 8, [139]) and placebo effects were significant [140].
Additionally, no difference was demonstrated in the effectiveness of one antidepres-
sant drug class over another (e.g., selective serotonin reuptake inhibitors; SSRIs; vs.
tricyclic antidepressants; TCAs), and in one-third of patients, depression was resis-
tant to monotherapy [140]. The addition of medications or switching within or
between drug classes appears to result in improved treatment response for these
patients [140, 141]. A meta-analysis of patient-level variables demonstrated that
duration of depressive symptoms and baseline depression severity significantly pre-
dicts response to antidepressant treatment in LLD, with chronically depressed older
patients with moderate-to-severe symptoms at baseline experiencing more improve-
ment in symptoms than mildly and acutely depressed patients [142].
Pharmacological treatment response appears to range from incomplete to poor in
LLD with co-occurring cognitive impairment. Of the MCI patients with dementia
that converted to AD over the course of their study, Modrego and Ferrandez [86]
found that the majority of these patients did not respond to antidepressant medica-
tions, and that no long-term improvements were observed if there was no response
to treatment within the first 2 months. These findings were posited as a potential
clinical indicator of the risk of conversion to AD. In a non-cognitively impaired

sample, in contrast, Gallassi and colleagues [143] found that at 6-month follow-up,
33 of the 42 depressed older adults sampled experienced remission of depressive
symptoms following administration of antidepressant medication (i.e., fluoxetine or
reboxetine) at baseline. Additionally, performance on memory tests improved from
baseline to 6-month follow-up, though notably, remained significantly worse than in
age- and education-matched non-depressed controls. This study was limited to the
assessment of memory and performance on a general cognitive screening measure
(i.e., the Mini Mental Status Exam); executive functioning and processing speed
were not assessed. Additionally, control participants were only assessed at one time
point; therefore it is not clear to what extent practice effects may account for the
improvements found in memory performance for the depressed participants.
Bhalla and colleagues [144] also assessed cognitive functioning (i.e., processing
speed, memory, visuospatial, language, and executive functioning) in LLD patients
before and after successful psychopharmacological treatment and remission of
depressive symptoms and compared their performance to that of a non-depressed,
age- and education-matched control group. In this study, the control group was also
re-administered the same cognitive tests 1 year later. Results indicated that both
groups improved on testing at follow-up at approximately the same rate, indicating
a significant practice effect for the cognitive assessment. The authors compared the
performances at baseline and follow-up for each individual participant and found
that, despite improvement in the group mean for cognitive functioning and remis-
sion in depressive symptoms, LLD participants who were impaired at baseline
remained impaired at Time 2, and further, one-fourth of the LLD participants who
were cognitively intact at baseline were found to be impaired at follow-up. Similarly,
a study by OBrien and colleagues [145] found that, despite practice effects and
improvement in the severity of depressive symptoms at 6-month follow-up, the
depressed group continued to perform significantly worse on cognitive testing com-
pared to non-depressed controls. Additionally, structural differences in the brain
associated with depression, namely reduced hippocampal volume, were found to
account for 17 % of the variance in memory performance at follow-up. These stud-
ies suggest a chronic decrement in cognitive functioning associated with LLD that
is not adequately addressed through improvement of depressive symptoms alone.
Furthermore, non-response to standard treatment with antidepressants has been
found to be associated with vascular risks and poor cognitive functioning. A study
by Sheline and colleagues [146] demonstrated that processing speed, executive
functioning, episodic memory, and language functioning predicted remission at
3-month follow-up after initiation of antidepressant medication (i.e., nortriptyline),
and that WMH burden was significantly associated with both depression severity
and neuropsychological performance. Simpson et al. [147] also demonstrated the
predictive power of neuropsychological functioning and WMH burden in response
rates to standard treatments for depression, including psychopharmacological and
ECT. In particular, severity and confluence of WMH in the pontine reticular forma-
tion and basal ganglia were significantly associated with treatment non-response.
Iosifescu et al. [148] demonstrated this association between WMH and treatment
response in younger depressed subjects as well, though found that left hemisphere
WMH predicted lower rates of treatment response and remission, whereas total
WMH severity score did not.
Psychotherapeutic interventions have also been explored to address the significant
disability associated with LLD. Results of a meta-analysis by Pinquart and col-
leagues [149] demonstrated comparable effect sizes for psychotherapy and pharma-
cotherapy in LLD and suggested that psychotherapy may be more effective than
antidepressants in the treatment of milder forms of depression, such as dysthymia.
Another meta-analysis by Cuijpers and colleagues [150] identified 25 studies of the
effects of psychological treatment on depression in older adults and determined that
psychotherapy is effective in reducing depressive symptoms. No significant differ-
ence in effect size was found among the therapies utilized, which included cognitive
behavioral, interpersonal, and problem-solving focused therapies. Alexopoulos and
colleagues [151] suggested that problem-solving therapy (PST) could prove particu-
larly beneficial to LLD patients by addressing both the mood and executive dysfunc-
tion components that contribute to the significant disability associated with LLD. PST
is generally administered as a time-limited, semi-directive, skill-building focused
treatment, using psychoeducation to assist participants in identifying problems, gen-
erating possible solutions, effectively weighing the costs and benefits of solutions to
determine an appropriate course of action, and assessing the effectiveness of the
chosen solution (see [152]). A study by Arean and colleagues [153] found that PST
modified for use in a primary care setting resulted in better outcomes (i.e., fewer days
depressed and less severe symptom ratings) for older, depressed patients than stan-
dard community-based psychotherapy at 12-month follow-up. In a randomized, con-
trolled treatment outcome study, Alexopoulos and colleagues [154] compared the
effects of PST and supportive therapy on functional disability (assessed using the
World Health Organization Disability Assessment Scale, 2nd edition) and severity of
depressive symptoms in a sample of 201 depressed older adults with executive func-
tioning impairments. Participants were assessed at baseline and at 12-, 24-, and
36-weeks post-treatment. Those who completed PST demonstrated significantly
greater reductions in functional disability ratings compared to the supportive therapy
group and maintained therapeutic gains made over the supportive therapy group at
later follow-ups. Additionally, response to PST was significantly associated with
poorer executive functioning and a greater number of depressive episodes at baseline,
suggesting that this population of difficult-to-treat older adults may differentially
benefit from this therapeutic approach.
5.9 Conclusion
There is now a wealth of evidence to support the association between vascular

pathology and depression in older age. While the etiology of depression in older age
is multifactorial, from the epidemiological, neuroimaging, behavioral, and genetic
evidence available, we can conclude that vascular depression represents one impor-
tant subtype of LLD. The mechanisms underlying the relationship between vascular
pathology and depression are likely multifactorial, and may include disrupted
connections between key neural regions, reduced perfusion of blood to key brain
regions integral to affective and cognitive processing, and inflammatory processes.
There is also a growing interest into the role of genetic factors that may improve
ability to predict which adults are at greatest risk of developing depression late in
life. There are promising treatment prospects on the horizon for vascular depres-
sion, both pharmacological and behavioral. Continued work into the underlying
neurobiology of the condition will help to formulate more targeted and effective
prevention and treatment strategies.
Acknowledgements The authors thank Dr. Jon-Kar Zubieta and Ms. Chhavi Rastogi for their
assistance with manuscript editing.
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Measurement and Assessment
in Late-Life Depression 6
Olivia I. Okereke
Abstract
This chapter addresses the measurement and assessment of depression among
older adults, with a view toward its importance in developing optimal depression
prevention strategies. Overview is provided regarding commonly used dimensional
and categorical measures of depression. Specific examples of depressive symptom
scales as well as structured and semi-structured diagnostic interviews are described
in detail. Special attention is placed on relative advantages and limitations of each
measure or assessment method. Evidence for the reliability and validity of instru-
ments for the measurement of depressive symptoms specifically among older
adults is discussed in detail and illustrated in accompanying tables.
Keywords
Measures Scales Depressive symptoms Geriatric Structured interview
Diagnosis Dimensional Categorical Reliability Validity
6.1 Overview
Optimal approaches to measurement and assessment of depression and depressive

symptoms differ among older versus younger adults. First, symptoms featured on
common depression screening tools may be more likely to overlap among older
persons with physical or other symptoms that are not actually related to depres-
sion. Second, at the individual item level, some questions/items may show dif-
ferential functioning with regard to detecting true depression among older persons.

181 Longwood Avenue, 3rd Floor, Boston, MA 02115, USA

84 O.I. Okereke
Third, the thresholdsor cut pointsfor detecting depression may differ among
older versus younger adults even when using the same questionnaire; these differ-
ences may be more pronounced among older persons with co-morbidity and may
also show ethnic and/or cultural variation. Thus, careful attention to issues in
depression measurement and assessment will be critical to late-life depression
prevention.
This chapter will provide an overview of several common methods and specific
tools to measure depressive symptoms and assess presence of depressive disorders
among older adults. Broadly, both brief screening tools and detailed assessment
methods will be discussed. Benefits of screening tools include: (1) brevity, (2) ease
of use for patients and/or providers, (3) adaptability to self-report/self-administration,
(4) usefulness in monitoring symptoms and/or treatment response, and (5) applica-
bility to larger-scale preventive interventions. Potential shortcomings of these meth-
ods include: (1) reduced specificity for clinical depression, (2) lack of opportunity to
clarify or expand upon symptoms, and (3) susceptibility to gender, cultural or age
item biases. By contrast, detailed assessment methods tend to be lengthyrequiring
from 30 minutes to one hour to administer. However, many such assessments provide
the highest specificity not only regarding current symptoms or diagnoses but also
with respect to past history of depression, number of episodes and overall course.
Other benefits include: (1) the use of structured or semi-structured formats, which
tend to improve reliability of diagnosis over unstructured formats, (2) high level of
training that is typical of the administrator of such an assessment, and (3) the ability
to account for psychiatric co-morbidityincluding conditions (e.g., active substance
abuse) that may better explain a given persons symptoms. However, due to their
length, high requirements for administrator/interviewer training and burden from the
patients perspective, these types of interviews tend to be utilized primarily in the
research setting.
6.2 Commonly Used Brief Measures and Screeners

in Late-Life Depression
Several depression measures have achieved widespread use for the evaluation and
screening of depression, including among older adults. Key aspects of these
measures are summarized in Table 6.1.
The Centers for Epidemiologic Studies Depression Scale, or CES-D [1], is
among the most popular depression screening measures in research. The CES-D
can also be used to screen for both depression in very old populations [2]. Long
forms (20 items) and short forms (e.g., 10 items) [3, 4] are available; the abbrevi-
ated ten-item version of the CES-D [4] takes <5 min to complete on average.
Furthermore, both Likert-style [3] and binary (yes/no) [4] formats are available for
the ten-item version, further increasing ease of administration. Reliability of the
CES-D, as assessed using measures of internal consistency, for example, is reported
to be high [4, 5]. Additionally, cut points for clinically significant depressive symp-
toms have been created for long (16 points) and short versions of the CES-D
6 Measurement and Assessment in Late-Life Depression 85
Table 6.1 Selected depression brief evaluation and screening measures and their key features
Features
Can be Includes Possible cut points for
mapped item on MDD or clinically Average
Number Response to DSM suicidal significant depressive completion
Measure of items format criteria ideation symptomsa times
PHQ-9 9 4-Point Yes Yes 10, or algorithm <5 min
Likert
GDS-15 15 Yes/no No No 5 <5 min
CESD-10 10 Yes/no, or No No 4 For yes/no format; <5 min
4-point Likert 10 for Likert format
BDI-II 21 4-Point Yes Yes Variable; Beck et al. 510 min
Likert [28] suggest score
ranges: minimal
(013), mild (1419),
moderate (2028),
and severe (2963)
CES-D 20 4-Point No No 16 510 min
Likert
CES-D- 20 4-Point Yes Yes 16 510 min
revised Likert
a
Refer to Table 6.2 in this Chapter for more details regarding the validated cut points for these
measures when compared to diagnostic, gold-standard interviews
(10 points is suggested for the 10-item Likert-style version [3], and 4 points for the
binary format version) [4, 6]; however, as illustrated in Table 6.2 of this chapter,
variation has been observed in the optimal cut points for identifying depression
among older adults [79]. The key aspect of the CES-D is that the symptoms focus
heavily on core affective aspects of depressionsuch as feelings of being sad,
depressed, fearful, or hopeless. Thus, a potential limitation of the CES-D is that
depressed individuals who do not respond to items with a high focus on the affec-
tive aspects of depression may not be detected as such by the CES-D. This is a
particular challenge among older adults, among whom the state of anhedoniaas
opposed to expressed, subjective sadnessmay be the dominant feature of depres-
sion [4, 6]. A related limitation is that of item bias, or differential item-functioning.
For example, in an analysis [10] among a large-scale Australian cohort of women,
there was notable response variation for one item on the CES-D: older women,
compared to younger women, were substantially more likely to be missing
responses some items (e.g., I felt hopeful about the future); although the precise
explanation for this missing pattern is not clear, it is possible that it may have been
more challenging for the oldest versus younger women to answer a question related
to speculating on future time. Other investigators have found evidence of item-
response bias among older adults by race/ethnicity on the CES-D [11, 12].
Furthermore, the development of the CES-D pre-dated the advent of the modern
criteria for major depression (which emerged with the publication of the Diagnostic
Table 6.2 Comparisons of common brief depression scales with diagnostic gold standards in late-life depressiona
86
Study authors Gold

(location) Year Study population N Brief scale standard Author findings
Haringsma 2004 Dutch community residents 318 CES-D MINI ROC analysis found cut-off score of 25 to be optimal for MDD
et al. (Leiden, aged 5585 years who (sensitivity = 0.85, specificity = 0.64) and 22 for clinically
The referred themselves to relevant depression (sensitivity = 0.84, specificity = 0.6)
Netherlands) depression prevention
program
Beekman et al. 2002 Dutch adults between 55 and 277 CES-D DIS Using a cutoff score of 16 for MDD, sensitivity was 1 and
(Amsterdam, 85 years old, enrolled in the specificity = 0.88
The Longitudinal Aging Study
Netherlands) Amsterdam
Lyness et al. 1997 Patients 60 of 3 primary 130 GDS, SCID ROC analyses found that using a cutoff point of 21 on the
(Rochester, care practices in Rochester, GDS-15, CES-D for MDD, sensitivity = 0.92 and specificity = 0.87. A
NY) NY CES-D cutoff point for MDD of 10 on the GDS resulted in a sensitivity
of 1 and specificity of 0.84. A cutoff of 5 on the GDS-15 had a
sensitivity of 92 % and a specificity of 81 %. All scales lost
accuracy for detection of minor depression
Irwin et al. 1999 Patients 60 enrolled in 68 CES-D-10 SCID An optimal cutoff point of 4 was found for major depression
(San Diego, university-affiliated primary (sensitivity = 1, specificity = 0.92). The ten-item CES-D appeared
CA) care clinics as effective at screening for depression as the original CES-D
Blank et al. 2004 Patients 60 from urban 360 CES-D-10, DIS The GDS-15 had the highest sensitivity/specificity when used to
(Hartford, CT) primary care practices, GDS-15 screen for major depression in nursing homes (sensitivity = 0.86,
nursing homes and a hospital specificity = 0.82 using cutoff of 6). The CES-D-10 performed
better than other instruments in clinics (sensitivity = 0.79,
specificity = 0.81 using cutoff of 4) and hospital settings
(sensitivity = 0.92, specificity = 0.77)
Nyunt et al. 2009 Adults 60 living in 4,253 GDS-15 SCID Using cutoff of 5 for MDD, sensitivity was 0.97 and specificity
(Singapore) communities or nursing was 0.95
homes
O.I. Okereke
6
Chen et al. 2010 Patients (aged 60) of 77 PHQ-9, SCID When using a cutoff point of 9 for major depression, the
(Huangzhou, primary care clinics in PHQ-2 PHQ-9 had a sensitivity of 0.86 and specificity of 0.77. The
China) Huangzhou PHQ-2 was also found to be an effective screening tool, with
sensitivity = 0.84 and specificity = 0.9 using the cutoff of 3
Marc et al. 2008 Adults aged 65 receiving 526 GDS-15 SCID The optimal cutoff point for major depression was found to be
(Westchester, home care from a visiting 5, which yielded sensitivity = 0.72 and specificity = 0.78
NY) nurse service agency
Lamers et al. 2008 Patients 60 of general 105 PHQ-9 MINI For ADD (any depression), a cutoff of 6 for the summed
(Maastricht, practices in The Netherlands PHQ-9 score was used, and corresponded to sensitivity = 0.96
The and specificity = 0.81. The cutoff point 7 was used for MDD,
Netherlands) with sensitivity = 0.92 and specificity = 0.78. When using the
algorithm-based score of the PHQ-9 instead of the summed
score, the test for both ADD and MDD had low sensitivity
Ros et al. 2011 Older adults with or without 623 CES-D CIDI Among participants without cognitive impairment, the optimal
(Albacete, cognitive impairment cut-off point was found to be 28, with sensitivity = 0.82 and
Spain) specificity = 0.94. The optimal cut-off point among those with
cognitive impairment was just 13, however, which resulted in
sensitivity = 0.86 and specificity = 0.72
Mitchell et al. 2010 Older adults in medical 4,969 GDS-30, Semi- Meta-analysis found the GDS-30 to have a sensitivity of 0.82
Measurement and Assessment in Late-Life Depression
(Leicester, inpatient/outpatient settings GDS-15, structured and a specificity of 0.78. The GDS-15 had sensitivity = 0.84 and
UK) and in nursing homes GDS-4 psychiatric specificity = 0.74, and the GDS-4 was found to be the most
interviews effective at screening for depression in medical settings, with
sensitivity = 0.93 and specificity = 0.77
Watson et all 2009 Adults 65 in residential 112 GDS-15, SCID Using the cutoff point of one positive answer as criterion for
(Chapel Hill, care/assisted living PHQ-2 depression, the PHQ-2 had sensitivity = 0.80 and
NC) communities specificity = 0.71. The GDS-15 had sensitivity = 0.60 and
specificity = 0.75 with a cutoff point of 5, and yielded
sensitivity = 0.73 and specificity = 0.65 when using a cutoff of 4
(continued)
87
88
Study authors Gold

(location) Year Study population N Brief scale standard Author findings
Bunevicius 2012 Mid-life and older adults 522 BDI-II MINI A cutoff point of 14 produced a sensitivity of 0.89 and
et al. (Palanga, with coronary disease (mean specificity of 0.74 for MDD as diagnosed by the MINI
Lithuiana) age = 58 years; range 3277
years)
Frasure-Smith 2008 Mid-life and older adults 811 BDI-II SCID A cutoff point of 14 produced a sensitivity of 0.91 and
and with coronary disease (mean specificity of 0.78 for DSM-IV MDD
Lesprance age = 60 years; SD = 10
(Montreal, years)
QC, Canada)
Huffman et al. 2010 Mid-life and older adults 131 BDI-II SCID A cutoff point of 16 produced a sensitivity of 0.88 and
(Boston, MA) with coronary disease (mean specificity of 0.92 for DSM-IV MDD
age = 62 years; SD = 12.5
years)
a
Studies assessing the BDI-II did not focus exclusively on the late-life population but included samples with a mean age of approximately 60 years or greater
O.I. Okereke
and Statistical Manual of Mental Disorders III, or DSM-III in 1980); thus, the
items do not explicitly map to all of the DSM criteria for major depressive disorder
(MDD). Consequently, a revised version of the CES-D was recently developed by
Gallo [13]. The CES-D-revised is a 20-item scale with a similar Likert response
format, and it provides increased emphasis of symptoms of depression as they may
be experienced by older persons (e.g., more questions related to anhedonia and less
reliance on subjective sadness) and also includes questions about thoughts of
death/self-harm. In addition, unlike the original CES-D, the CES-D-revised can be
mapped directly to the criteria of the DSM-IV [14].
Another scale that has achieved widespread use, as has the CES-D, is the
Geriatric Depression Scale (GDS) [15]. The Geriatric Depression Scale is a
self-report instrument measuring depressive symptoms in older adults [15, 16].
The scale is designed to identify symptoms that distinguish depression in the elderly
from dementia. The GDS is comprised of the affective (e.g., sadness, apathy, cry-
ing) and cognitive (e.g., thoughts of hopelessness, helplessness, guilt, worthless-
ness) symptoms of depression in the elderly [17]. It downplays the somatic items
(e.g., disturbances in appetite, sleep, energy level, and sexual interest) that many
suggest are important confounds among older adults [18, 19]. For example, com-
pared with younger depressed adults, depressed older persons tend to present more
often with somatic symptoms (e.g., general somatic and gastrointestinal symptoms)
and hypochondriasis [20].
Available in both long (30-item) and shorter versions (e.g., the commonly used
GDS-15, with 15 items)the shorter version [15] (GDS-15) with a yes/no response
format was developed to decrease fatigue or lack of focus that may be experienced
by older persons [21]the GDS has several advantages, and its 15-item format is
primarily used in the context of brief screening and assessment. First, the yes/no
response format allows for brevity in administration, and scoring is very straightfor-
ward for the busy clinician [7, 22]. Validated cut points have been published both
for older adults in primary care settings and also for older adults with specific co-
morbidities (see Table 6.2 for details) [6, 7, 17]. Moreover, as its name implies, the
GDS-15 has particular value for detecting late-life depression because featured
items also emphasize symptoms that may be most relevant to the experience of
depression in older personsespecially several questions honing in on anhedonia
(e.g., items re: dropping activities, not doing new activities, boredom, emptiness) [6,
17]. Potential limitations include a decrease in the kind of dimensionality (i.e., abil-
ity for symptom scores to be expressed on a broader continuum) than is possible
with the Likert-style CES-D and other measures, as well as the inability to map
directly to DSM diagnostic criteria for MDD; the latter is not surprising, however,
aslike the CES-Dthe original development period of the GDS pre-dated the
era of the modern DSM criteria. Another potential limitation of the GDS-15 is that
the items do not feature emphasis on appetite/weight or sleep disturbance; such
symptoms are not only potentially relevant to detecting depression but also allow for
discrimination of subtypes of depressionfor example, typical (reduced appetite/
weight, decreased sleep, etc.) versus atypical (increased appetite/weight, hypersom-
nia, etc.) [2325]. Nevertheless, there is some evidence that dimensionality in the
90 O.I. Okereke
GDS-15 is likely adequate. For example, in a recent analysis of long-term depres-

sion patterns in a large cohort of older female adults, Byers et al. were able to
employ repeated measures of the GDS-15 in order to derive distinct latent sub-
groups of depression trajectories [26].
The Beck Depression Inventory, or BDI, is another widely used measure [27].
Although the original BDI was developed by Aaron Beck in the 1960s, the most
commonly used form is the 21-item BDI-II [28]. Importantly, the BDI-II, unlike its
predecessor, was developed in light of the newly available diagnostic criteria for
MDD in the DSM nosology. The Beck Depression Inventory (BDI) is a valid instru-
ment for the diagnosis of depression in older adults [29]; there is also a seven-item
BDIPC which is an abbreviated primary care version of the BDIII, but it has not
been specifically tested in elderly medical patients [30]. Validation studies have
found the BDI-II to be effective at screening for depression in middle-aged and
older adults with coronary disease, even though it contains several questions regard-
ing somatic symptoms that could act as confounders [27, 31, 32]. Like the GDS, the
BDI-II incorporates more aspects relevant to the behaviors and cognitions in depres-
sion, as opposed to the relatively greater emphasis on the affective elements seen in
the CES-D [32]. The BDI-II enjoys advantages of reliability, validity, dimensional-
ity, sensitivity to change (useful in context of symptom monitoring), and applicabil-
ity in assessing a broad range of aspects in depression, including the elements of
typicality versus atypicality [33, 34]; although, its 21-item length renders it less
practical than other screeners, especially in the primary care context [29]. Also, less
is known about the BDI regarding differential item functioning and any concerns
regarding its use in culturally diverse contexts. Finally, there have been concerns
about overlapping symptoms between medical conditions and the depressive
somatic symptoms on the BDI [33], and some elderly individuals may not be able
to complete the scale due to reading difficulty, physical debility, or compromised
cognitive functioning [34].
A measure that has rapidly emerged as a screener of choice among many experts
[35] is the Patient Health Questionnaire-9. Originally developed in 1990s as part of
the PRIME-MD (Primary Care Evaluation of Mental Disorders) by Spitzer,
Williams and Kroenke [36], the PHQ-9 is now publicly available and features a
Likert-style response format for easy self-administration and rapid scoring by the
clinician. The PHQ-9 has been shown to be effective and efficient as a depression
screening tool for older adults in primary care settings [37] and has been success-
fully used to identify depression in homebound older persons [38]. It has high reli-
ability and has been extensively validated in a variety of contexts [3945]; both a
diagnostic algorithm and cut point (of 10 points or above) have been validated for
the PHQ. Furthermore, the measure has dimensionality and demonstrated sensitiv-
ity to change [40, 41], both of which are useful in the context of tracking symptoms
among persons under treatment or monitoring persons at risk for depression. Among
commonly used measures, the PHQ-9 was designed to map most directly to the
modern criteria for major depression in the DSM [46]. To increase applicability, an
eight-item version (PHQ-8) is also available and it removes the item pertaining to
thoughts of death/suicide, as this may be inappropriate in certain large-scale
screening contexts where rapid clarification and follow-up is not possible; however,
current evidence shows that the validated cutoff of the PHQ-8 has comparable sen-
sitivity and specificity for depression as the original nine-item version [47]. A two-item
version of the PHQ has also performed well in validation studies, and has been
recommended for initial depression screening due to its brevity [48, 49]. Unlike
most other screeners, the PHQ also does not show any evidence of differential item
functioning that was observed for other measures [42, 43]. In part because of the
attributes noted above, the PHQ has gained traction as a screener and has been rec-
ommended for the purpose by a variety of agencies/organizations, and Medicare has
integrated the PHQ-9 into the revised Minimum Data Set assessments (MDS 3.0)
for nursing home residents [50]. (For more re: policy, see Table 9.1 in Chap. 9.)
6.3 Detailed Assessments for Late-Life Depression
The preceding section introduced several popular and well-regarded measures in

widespread use for the brief evaluation and/or screening of depression among older
adults. However, it is generally recognized that sole administration of such brief mea-
sures to older persons would not be insufficient for diagnosing or characterizing clini-
cal depression. Rather, brief measures have the advantage of identifying persons who
may be experiencing depression but would otherwise go undetected; further evalua-
tion, using a detailed clinical interview for example, and/or treatment would be war-
ranted following a positive screen using one of those brief measures.
Several detailed assessments have been developed for the purposes of diagnosing
and characterizing depression. For reasons that will be made evident in the Chapter,
these detailed assessments cannot have broad utility in primary care settings and are
almost exclusively applied in research contexts. However, these methods for detailed
evaluation have been essential in mental health research, and in conduct of late-life
depression research specifically; thus, overview and description are provided here.
Overall, the major advantages of the detailed assessments include: (1) high spec-
ificity for diagnosis, (2) improvements in reliability compared to unstructured and/
or open-ended clinician interviews, (3) incorporation of both symptom and func-
tional (i.e., presence of social or occupational impairment due to symptoms) aspects
of depression into making the diagnosis, and (4) the ability to incorporate the obser-
vations of a trained interviewer. This last advantage can be critical in the assessment
of older persons; given the higher likelihood that older persons may deny overt
sadness [13], which would be relatively easy to do on a self-report questionnaire, a
sensitive and well-trained interviewer may be able to overcome this issue by prompting
more accurate responses or obtaining clarifications that allow for accurate coding of
responses.
Regarding limitations, these detailed assessments have many in common, but to
varying degrees. First, the length and time burden tends to be substantial. More
streamlined semi-structured interviews [51] may take on average a half-hour; how-
ever, some require 2 h or more, depending on how many symptoms are endorsed
by the patient. Second, these interviews necessitate considerable training of the
92 O.I. Okereke
administrators, in order to optimize fidelity and, thus, reliability; some can only be
administered by persons with specific mental health clinical training. A third, but
relatively underappreciated potential limitation, is that there is inadequate informa-
tion regarding the vulnerability of these interview formats to cultural biases.
Finally, an important limitation is that these interviews tend to lack dimensionality,
as the emphasis is placed on categorical diagnosis.
The first detailed assessment to be aligned with the modern criteria for major
depression in the DSM was the Diagnostic Interview Schedule (DIS) [52]. The DIS
was developed and implemented in the context of one of the largest and historically
important psychiatric epidemiology studies, the Epidemiologic Catchment Area
(ECA) program [53]. The DIS operationalized disorder criteria as they appeared in
the DSM-III, which was published in 1980. The DIS is a fully structured interview
that allows reporting from patients/respondents such that over two dozen different
diagnoses can be determined by trained interviewers using fully described algo-
rithms and later using computerized formats [54].
Highly similar to the DIS, the Composite International Diagnostic Interview
(CIDI) was actually developed as an extension or expansion upon the original DIS
and was first published by the World Health Organization (WHO) in 1990 [55];
several versions and updates have been published since then. The CIDI is a fully
structured interview that can be administered by laypersons; it has the advantage of
relating to both the DSM as well as the International Classification of Diseases
(ICD) nosologiesthus, making cross-national/cross-cultural comparisons more
feasible. Although it is not required that CIDI administrators have clinical back-
grounds, specific training is still necessary for its valid use. Like the DIS, the CIDI
now includes computerized administration formats.
By way of contrast with fully structured interview formats such as the DIS and
the CIDI, the SCIDor Structured Clinical Interview for DSM Disordersis one
of the best known semi-structured interviews [56]. Because of its semi-structured
format, which entails the ability to ask appropriate follow-up and clarifying ques-
tions as well as to incorporate clinician experience and observations, the SCID
should be administered by clinicians or other trained mental health professionals,
not laypersons. Although persons with fewer symptoms may take less time to inter-
view, average administration time may be around 2 h. The allowances involved in a
semi-structured format may raise questions regarding the reliability of the SCID;
however, high reliability of the SCID has been established [57, 58], including
among older persons [59]. The SCID has been applied in non-English language/
non-primary English language cultures and similarly has been found to have good
reliability and discriminant validity [60, 61]. Although the SCID can be used by
clinicians in the practice setting, the most popular usage of this instrument is in the
research setting.
Finally, another major semi-structured interview that has obtained wide-reaching
use is the MINI, or Mini-International Neuropsychiatric Interview [51]named
consistently with its considerably shorter average administrative time when com-
pared with other diagnostic assessments. Versions of the MINI that focus primarily
on elaborating current diagnosesbut not routinely on determining lifetime
diagnoses of psychiatric disorders in all categoriesmay take on average less than

half an hour to complete. As expected, however, the MINI requires considerable
experience and expertise on the part of the clinician interviewer; although it is pos-
sible for non-clinicians to administer this interview, it is not expected that this could
be achieved without extensive and rigorous training and testing of interviewers
especially as the interview incorporates some ratings based on direct clinician
observations and/or judgments. The MINI can also be administered alongside the
Sheehan Disability Scale (SDS) [62], created by one of the MINI developers.
Although fully and semi-structured interview formats are unlikely to gain traction
for broader use among older adults in primary care settings, the SDSwith a
brief, self-report format and easy-to-use visual analog designwould be more
applicable for rapid assessment of the degree of everyday functional impairment
that patients are experiencing due to depression.
As expected, efforts have been made to validate commonly used brief depression
scales against detailed interviews as the gold-standard (e.g., the DIS, CIDI, SCID,
and MINI) and to derive cut points for optimal sensitivity and specificity for clinical
depression. Table 6.2 summarizes cross-sectional studies that specifically conducted
such evaluations among older adults.
6.4 Future Directions in Measurement and Assessment

of Late-Life Depression
The aforementioned available brief and extended measures in late-life depression

have numerous strengths; there remain several potential weaknesses and limitations
that highlight the need for improvements. First, more work can be done to ensure
that validity and applicability of brief, self-report measures are optimized for older
persons; furthermore, it is essential to ensure that psychometric performance is
equally good among ethnically or culturally diverse older adults. Second, in order to
be applied in the setting of depression prevention, it is important that measures have
demonstrated sensitivity to change and can be used in a reliable and valid fashion to
track the course of symptoms among older persons at risk for depression. Third,
given the diversity of current measures in use, there is a need to ensure harmoniza-
tion and linkage across measures; this step will facilitate, for example, comparisons
of the impacts of late-life depression preventive interventions employed across
different care entities.
The road to harmonization may indeed be paved by an important innovation, and
key future direction, in measurement and assessment of late-life depression: use of
computerized adaptive testing (CAT). Already in broad use for a variety of pur-
posesfrom student standardized test administration to performance measurement
among professionalsCAT may represent an ideal opportunity both for maximiz-
ing precision in the assessment of depressive symptoms among older persons as
well as for harmonizing different available measures to a common scale. For example,
a National Institutes of Health (NIH) Roadmap initiative called PROMIS, or Patient
Reported Outcomes Measurement Information System, has developed CAT
94 O.I. Okereke
methods to capture symptoms endorsed in a variety of domainsincluding depression

and general functioning [6366]. Critically, this system is designed to optimize
precision and minimize bias in measurement so that the true level of any given
person on the construct of interest can be captured by the attained score. A readily
apparent advantage of CAT is that it lends itself to direct self-administration by
patients. Furthermore, flexibility in the items generated by the computer allows for
considerable shortening of test items and total administration timeeven compared
to many existing brief scales. In addition, through the PROsetta Stone [67] effort,
PROMIS team leaders have developed methods for linking scores on PROMIS mea-
sures of constructs such as depression to comparable scores as they would appear on
above-mentioned scales in common use, such as the CES-D and PHQ-9.
Nevertheless, CAT has a number of important limitations, including some of the
technical complexity involved in item selection (and ensuring an adequately repre-
sentative pool of items), calibration, and valid scoring. Continued work is required
to ensure that high performance of PROMIS measures of depression can be achieved
among diverse groups of older persons and that, ultimately, the CAT interface can
be applied in the kinds of primary care contexts in which it may be most useful for
many older adults.
6.5 Summary
Numerous practical and self-administered measures are available for the assessment of
depression in later-life. Generally, brief measures have the greatest utility in the context
of screening for depression among older adults, and several measures have added use-
fulness in grading the severity of symptoms. Major advantages of such measures
include brevity and ease of use for both the patient and provider; the context of a busy
primary care practice, the importance of simplicity and time-efficiency cannot be over-
stated. Nevertheless, important potential disadvantages of brief measures include lack
of specificity: many people with higher scores on such measures (e.g., due to some
recent illness or other reason) may not actually have depression. Furthermore, it is criti-
cal in the screening context that administration of a quick screening not be regarded as
tantamount to diagnoses; indeed, use of these measures in a screening context assumes
that clinicians are prepared to provide appropriate follow-up as needed. Finally, ongo-
ing work is needed to ensure that brief scales adequately capture the symptoms of
depression as experienced by diverse older adults. Many of the above shortcomings of
brief measures are readily addressed by detailed assessments, which feature specificity
of diagnosis and detailed characterization of illness, including past episodes and/
course. However, the length and training requirements of these assessments limit their
usefulness beyond research settings. Therefore, an important potential advance in late-
life depression measurement would be the optimization of computerized adaptive test-
ing methods, which could join the practical aspects of brief measures, such as low time
and patient burden, ease of administration, rapid scoring and output of a dimensional
score, with the major advantages of the detailed assessmentshigh precision and
specificity for depression.
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Indicated Prevention
7
Pim Cuijpers, Claudia Buntrock, David Daniel Ebert,
Aartjan T.F. Beekman, and Charles F. Reynolds III
Abstract
Although most progress in the field of indicated and other types of prevention of
mental disorders has been made in children and adolescents, recent years have
also seen a considerable progress of research among older adults. This research
has resulted in a growing body of knowledge on how to identify those with the
highest risk of developing a mental disorder, several preventive interventions,
and some randomized controlled trials showing that (indicated) prevention may
be possible and effective in older adults.
Keywords
Depression Interventions Therapy
P. Cuijpers, Ph.D. (*)

Division Health Trainings Online, Leuphana University Innovation Incubator,
Lueneburg, Germany
e-mail: p.cuijpers@vu.nl
C. Buntrock, M.Sc.
Lueneburg, Germany
D.D. Ebert, Ph.D.
Department of Psychology, Clinical Psychology and Psychotherapy, Philipps University,
Marburg, Germany
Lueneburg, Germany
A.T.F. Beekman, M.D., Ph.D.

100 P. Cuijpers et al.
7.1 Introduction
Although most progress in the field of indicated and other types of prevention of
mental disorders has been made in children and adolescents, recent years have also
seen a considerable progress of research among older adults. This research has
resulted in a growing body of knowledge on how to identify those with the highest
risk of developing a mental disorder, several preventive interventions, and some
randomized controlled trials showing that (indicated) prevention may be possible
and effective in older adults [1].
Among the different types of preventive interventions, indicated prevention is the
most examined and most evidence-based approach to prevention in all age groups
[2, 3]. Indicated prevention is aimed at individuals who have some symptoms of a
(depressive) disorder but do not meet diagnostic criteria. Indicated prevention may
be aimed at two related but different goals. First, because subclinical depression can
be disabling in its own right, with a considerable impact on quality of life, interven-
tion may be necessary. The goal is thus to reduce depressive symptomatology and to
improve quality of life. The second goal of indicated prevention is to prevent the
onset of major depressive disorders by strengthening protective factors (e.g. social,
cognitive, or problem-solving skills) or alleviating prodromal disease stages
(e.g. educing severity of depressive symptoms).
The incidence rate of major depression in subjects with subclinical depression in
community studies ranges from 1 to 15 new cases per 100 person years, compared
with 05 in subjects without subthreshold depression [4]. This translates into inci-
dence rates of approximately 2025 % over 1 year. A recent meta-analysis showed
that it is unlikely that antidepressants and benzodiazepines have a clinically impor-
tant advantage over placebo in individuals with subclinical depression [5]. Therefore,
psychosocial treatments are usually preferred as (preventive) treatments in subclini-
cal depression, both for scientific reasons and by virtue of patient preferences.
In the past decades, several indicated interventions, aimed at older adults with
subclinical symptoms but no depressive disorder, have been developed. In this
chapter we will give an overview of interventions aimed at indicated prevention of
depression for older adults, and review the randomized trials that have been con-
ducted in this area. We will begin with a description of the Coping with Depression
course (CWD), which is the best studied preventive intervention in all age groups
[6, 7], including older adults [810].
C.F. Reynolds III, M.D.

7 Indicated Prevention 101
7.2 The Coping with Depression Course as Indicated

Prevention in Older Adults
The Coping with Depression course (CWD) is a cognitive behavioral intervention

for depression that has been examined in many studies as a treatment of depression
[7]. However, there are also many studies that have examined the CWD as a preventive
intervention.
The CWD is a psychoeducational intervention. In a psychoeducational treatment,
the participant works through a standardized psychological treatment protocol more
or less independently [7]. The standardized psychological treatment protocol can be
written down in book form, but it can also be available through other media, such as
a personal computer, Internet, CD-ROM, or television.
Psychoeducational treatments can be delivered in individual, group, or guided
self-help format. The group format is often used, but in recent years, the Internet is
used more and more in psychoeducational interventions, including the CWD for
older adults [9]. The psychoeducational approach implies that the therapist works
more in the role of an instructor or coach instead of a therapist, and the patient is
more a student than a traditional patient. This is important from the point of view of
the patient, who remains more in control of the therapy than in other interven-
tions, because he or she is the one who has to apply it to him- or herself. Because of
this, the CWD is often considered to be less stigmatizing than traditional therapy.
A second important characteristic of the CWD is the toolbox idea. This means
that in the course participants learn a series of many different skills that may help
them in coping with their depression and that more or less fit the theoretical model
of the CWD (see below). The skills which are trained in the original CWD focus on
social skills, skills in restructuring negative cognitions and behavioral activation to
increase pleasant events (activity scheduling). The cognitive skills include train-
ing in increasing thoughts associated with positive mood and decreasing thoughts
associated with negative mood, as well as elements from rational emotive therapy
[11] and cognitive therapy [12]. The behavioral activation approach has been devel-
oped by Lewinsohn and his colleagues [13]. Apart from these three approaches in
the original CWD, the contents of the course can easily be adapted to the needs of
the population and the goals of the intervention. For example, in the CWD for ado-
lescents conflict solving skills have been added and the materials are rewritten in a
more popular way. In the CWD for the elderly [14], the materials have been simpli-
fied. The basic approach is similar for each part of the skills training. First, during 1
or 2 weeks the participant collects information on the subject matter (negative
thought, pleasant/unpleasant events, stressful events, social events). Then, he or she
sets a goal for what he or she wants to change. He or she develops a systematic plan
to reach this goal. And finally he or she starts working with the plan, improves it and
examines if this plan alleviates the depression.
Another characteristic of the CWD is that it may in some cases be conducted by
health care professionals, other than psychologists or psychotherapists. In an early
study among older depressed adults participating in the CWD, no indications were
found that the groups led by 16 trained paraprofessional therapists in the study (indi-
viduals not working in mental health, but in senior centers and retirement hotels)
resulted in worse outcomes than the groups led by another 16 professional therapists
[15]. This does not imply that each version of the CWD can be applied by other
health care professionals. In fact, whether it can be applied by other professionals is
an empirical question which should be examined in each of the specific versions of
the CWD. However, the research that has been conducted is encouraging. And using
paraprofessionals in delivering interventions to (subclinically) depressed individuals
is potentially a cost saving. There is a serious shortage of funds for the public mental
health delivery system in many countries and using paraprofessionals may increase
the number of people who receive evidence-based interventions.
Theoretically, the CWD is based on social learning theory [16] according to which
treatment for depression involves increasing self-efficacy related to mood manage-
ment, using such skills as increasing pleasant and decreasing unpleasant person
environment interactions. The theoretical model of the CWD has been described in
detail elsewhere [17]. According to this model depression starts when environmental
changes, such as life events, disrupt the functioning of an individual in important areas
of behavior. The environmental changes can create vulnerability for depression when
they increase negative experience or decrease positive, reinforcing events. These
changes are expected to have a particularly negative impact among individuals who
have personal vulnerabilities to depression or lack factors that protect against depres-
sion, such as a supporting social network or effective coping skills. When life events
occur in the presence of personal vulnerabilities, a mediating step toward depression is
increased self-awareness: the tendency to focus on ones internal experience and to
self-monitor and self-analyze. Then the development of depressive symptoms becomes
a downward spiral in which the depression deteriorates, which in turn serves as a feed-
back element that sustains the cycle and potentially alters predisposing characteristics.
The CWD is aimed at changing this downward spiral into an upward spiral. By focus-
ing on positive interactions with the environment and changing negative cognitions, the
depression improves somewhat, which in turn stimulates the depressed individual to
have more positive interactions with the environment and think more positively.
The CWD has been shown to be a very flexible intervention which can be easily
adapted and modified for specific goals and target populations, without changing
the basic structure and ideas of the CWD. The CWD can and has been used in the
prevention of depression, in the treatment of depressed cases, and as maintenance
after successful treatment (for review see [7]). As we will see later on in this paper,
the CWD has also been adapted for the use in many different target groups, includ-
ing adolescents, older adults, minority groups, mothers of children with ADHD, and
primary care patients.
7.3 Other Interventions for Indicated Prevention

in Older Adults
In the past decades, several other indicated prevention interventions aimed at older
adults with subclinical symptoms but no mental disorder, have been developed. In the
following paragraphs, we will describe the interventions that have been examined in
a randomized controlled trial.
7.3.1 Problem-Solving Therapy
Problem-solving therapy (PST) is a brief and focused psychological intervention

that has been used with a variety of client groups including people with depression,
chronic illness, and suicidal thoughts and behaviors. It is a psychological treatment
in which patients systematically learn how to make an overview of the problems
they have and how to solve them. It usually contains several steps that have to be
taken to solve problems. First, the patient makes an overview of the problems he or
she has, then he picks one of the important problems and generates as many solu-
tions of this problem as possible. Then he selects the best solution with the highest
chance of success, and works out of a systematic plan for this solution. After this
has been done, the patient evaluates whether the solution has resolved the problem.
If not he goes back to the list of solutions and selects the next possible solution.
If the problem is solved, the patient can go back to the list of problems and select
the next problem that has to be solved, etc.
There are several subtypes of PST, such as PST according to Nezu [18] and
Mynors-Wallis et al. [19]. PST according to the method of Mynors-Wallis is the
briefest one (six sessions by a primary care nurse or a general practitioner) and has
been examined as a treatment for minor depression in one trial [20].
7.3.2 Interpersonal Counseling
Interpersonal counseling (IPC) is a brief version of Interpersonal psychotherapy

(IPT). IPT is a 16-session, highly structured manual-based psychotherapy that
addresses interpersonal issues in depression to the exclusion of all other foci of
clinical attention (http://www.interpersonalpsychotherapy.org). IPT has no specific
theoretical origin, although its theoretical basis can be seen as coming from the
work of Sullivan, Meyer, and Bowlby. The current form of the treatment was devel-
oped by the late Gerald Klerman and Myrna Weissman in the 1980s [21]. IPC has
been studied in one older study as a treatment of medically ill older adults with
subclinical depression [22].
7.3.3 Life Review and Reminiscence
Another preventive intervention for depression in older adults is life review and remi-
niscence. In life review interventions, older adults discuss their life and the evalua-
tion of each important period in their life with a trained professional. Several
randomized controlled studies and meta-analyses have shown that these interven-
tions are effective in reducing existing depressive symptoms [23], as well as on
enhancing life-satisfaction and emotional well-being [24]. Although the effects have
not yet been examined in target groups in which subthreshold depression was estab-
lished with a diagnostic interview, life review seems to be an excellent intervention
for indicated prevention, because of its low threshold for participation, because the
stigmatizing word depression is not needed, and because no understanding of
negative thoughts or other complex psychological issues are necessary for participating
successfully in this intervention. In a recent randomized trial the effects of life review
in older adults with subthreshold were examined [25], and it was found that life
review resulted in a significantly lower level of depressive symptoms when com-
pared to the inactive control group, who only viewed a general movie.
7.3.4 Internet-Based CBT as Preventive Intervention

in Older Adults
More recently, the Internet has been found to offer promising new opportunities for
the prevention of mental disorders in all age groups, including older adults. A consid-
erable number of studies have found that internet-based cognitive behavior therapy is
effective in the treatment of depressive disorders [9, 26, 27]. In one study, internet-
based CBT has been found to be effective in the treatment of subthreshold depression
in older adults [9]. This study showed that Internet-based CBT had large effects on
depressive symptomatology in older adults, and was as effective as a preventive
group intervention.
Using the Internet to provide (guided) self-help indicated prevention interventions
may help to overcome some of the limitations of traditional preventive services.
Web-based guided self-help strategies have several advantages over face-to-face
approaches. These include: (a) interventions are more easily accessible at any time
and place while anonymity is assured when patients want to avoid stigmatization, (b)
a greater potential for the integration of acquired skills in daily life due to an emphasis
on the participants active role in (guided) self-help interventions, (c) participants can
work at their own pace and go through materials as often as they want, (d) elimination
of travel time and costs for both participants and clinicians, and (f) web-based inter-
ventions may attract people who do not make use of traditional mental health services.
Finally (g), web-based interventions are easily scalable. Scalability means here that
web-based interventions shown to be effective under controlled conditions (i.e. ran-
domized controlled trial) can be easily expanded with only a small increase of thera-
peutic resources to reach a greater proportion of the eligible population.
However, while a considerable number of studies have found that Internet-based
cognitive behavior therapy is effective in the treatment of depressive disorders [27],
yet evidence is scarce for their potential regarding the prevention of depression in
older adults. In one study, Internet-based CBT has been found to be effective in the
treatment of subthreshold depression in older adults [9]. This study showed that
Internet-based CBT had large effects on depressive symptomatology in older adults,
and was as effective as a preventive group intervention.
7.3.5 Stepped-Care Models of Prevention
Another recent development is the use of stepped-care models for the prevention
of depressive disorders in older adults with subthreshold depression or anxiety [28].
In a large randomized controlled trial, older adults with subthreshold depression or
anxiety were recruited from primary care and assigned to a preventive stepped-care
program or usual care. Stepped-care participants sequentially received watchful
waiting, CBT-based bibliotherapy, CBT-based Problem Solving Treatment, and
finally referral to primary care for medication, if required. It was found that cumula-
tive incidence of DSM-IV major depressive disorder or anxiety disorder after
12 months was reduced from 0.24 (20/84) in the usual care group to 0.12 (10/86) in
the stepped-care group, which indicates a relative risk of 0.49 (95 % CI: 0.240.98).
These results are better than what was found in meta-analyses of preventive inter-
ventions for depression [2, 3, 6], and may indicate that stepped-care is an excellent
method for the prevention of mental disorders in older adults.
7.4 Research on Indicated Prevention of Depression

in Older Adults: Way
We recently conducted a meta-analysis of studies examining psychological treat-

ments of subclinical depression [41]. In seven studies, the effects of preventive
interventions on older adults with subclinical depression were examined. In this
paragraph, we will summarize the results.
For the identification of relevant studies, we used a database of 1,476 papers on the
psychological treatment of depression that has been described in detail elsewhere
[2, 3], and that has been used in a series of earlier published meta-analyses (www.
evidencebasedpsychotherapies.org). This database is continuously updated through
comprehensive literature searches (from 1966 to January 2013). In these searches we
examined 14,164 abstracts in Pubmed (3,638 abstracts), PsycInfo (2,824), Embase
(4,682), and the Cochrane Central Register of Controlled Trials (3,020). These
abstracts were identified by combining terms indicative of psychological treatment
and depression (both MeSH terms and text words). For this database, we also checked
the primary studies from 42 meta-analyses of psychological treatment for depression
to ensure that no published studies were missed (www.evidencebasedpsychotherapies.
org). From the 14,164 abstracts (10,474 after removal of duplicates) 1,476 full-text
papers were retrieved for possible inclusion in the database.
We included (a) randomized controlled trials in which (b) a psychological inter-
vention (c) was compared to a control condition (d) in older adults (e) with clini-
cally relevant depressive symptoms, (f) but no major depressive disorder or
dysthymia, (g) as established with help of a standardized diagnostic interview (such
as the DISC, CIDI, or SCAN) to exclude the presence of full-blown mood disorder
at pretest. Clinically relevant depressive symptoms are defined as scoring above a
cut-off score on a self-rating depression questionnaire; scoring above a cut-off score
on a clinician-rated instrument; or meeting criteria for minor depression according
to the criteria described in the DSM, ICD, or Research Diagnostic Criteria. We also
included studies in which subjects with a diagnosed depressive disorder were
included, but only when the results specifically reported for subjects with subclini-
cal depression. Studies examining stepped-care models for the treatment of depres-
sion were also included, as these usually have a strong focus on psychological
treatments.
We assessed the validity of included studies using four criteria of the Risk of bias
assessment tool, developed by the Cochrane Collaboration [29]. This tool assesses
possible sources of bias in randomized trials, including the adequate generation of
allocation sequence; the concealment of allocation to conditions; the prevention of
knowledge of the allocated intervention (masking of assessors); and dealing with
incomplete outcome data (this was assessed as positive when intention-to-treat
analyses were conducted, meaning that all randomized patients were included in the
analyses).
In addition to indicators of study quality, we coded several aspects of the included
studies, including participant characteristics (recruitment method: community, from
clinical samples, or other; target group: adults in general, or more specific target
groups such as older adults), intervention characteristics (format: individual, group,
or guided self-help; number of sessions; and type of psychotherapy: cognitive
behavior therapy, or other type); and study characteristics (type of control group:
care-as-usual or other).
For each comparison between a psychotherapy and a control group, the effect
size indicating the difference between the two groups at post-test was calculated
(Hedgess g). Effect sizes were calculated by subtracting (at post-test) the average
score of the psychotherapy group from the average score of the control group, and
dividing the result by the pooled standard deviation. Because several studies had
relatively small sample sizes, we corrected the effect size for small sample bias
according to the procedures suggested by Hedges and Olkin [30].
In the calculations of effect sizes, we only used those instruments that explicitly
measured symptoms of depression, such as the Beck Depression Inventory [31], or the
HAM-D [32]. If more than one depression measure was used, the mean of the effect
sizes was calculated, so that each comparison yielded only one effect. If dichotomous
outcomes were reported without means and standard deviations, we used the proce-
dures of the Comprehensive Meta-Analysis software (version 2.2.021) (see below) to
calculate the standardized mean difference. To calculate pooled mean effect sizes, we
used the computer program Comprehensive Meta-Analysis. As we expected consider-
able heterogeneity among the studies, we employed a random effects pooling model.
Because the standardized mean difference (Hedges g) is not easy to interpret from a
clinical perspective, we transformed these values into the number-needed-to-treated
(NNT), using the formulae provided by Kraemer and Kupfer [33]. The NNT indicates
the number of patients that have to be treated in order to generate one additional
positive outcome [34].
As a test of homogeneity of effect sizes, we calculated the I2-statistic which is an
indicator of heterogeneity in percentages. A value of 0 % indicates no observed
heterogeneity, and larger values indicate increasing heterogeneity, with 25 % as low,
50 % as moderate, and 75 % as high heterogeneity [35]. We calculated 95 % confi-
dence intervals around I2 [36], using the non-central chi-squared-based approach
within the heterogi module for Stata [37]. We also calculated the Q-statistic, but
only report whether this was significant.
7.5 Research on Indicated Prevention of Depression

in Older Adults: Results
We included seven studies with a total of 928 participants, 502 in the indicated
prevention groups and 426 in the control groups (see also [41]). Selected character-
istics of the included studies are presented in Table 7.1.
Four studies were conducted among older adults in general, one in nursing home
residents, one in medically ill older adults, and one among older primary care
patients. There were eight comparisons between an indicated intervention and a con-
trol group (one study compared two treatments with a control group; [9]). The inter-
ventions in the six studies included the Coping with Depression course (3 studies),
life review, problem-solving therapy, interpersonal counseling, and stepped-care
(1 study each). In four interventions a group format was used, three used an indi-
vidual format and one used an Internet-based intervention. The number of sessions
ranged from 6 to 13. Four studies were conducted in the Netherlands, two in the
United States, and one in Canada. The quality of the studies varied. Four studies
met all four quality criteria, while the other three only met one of the four criteria. In
three studies a care-as-usual control group was used, in two studies a waiting-list
control group, in one study a pill placebo and in the final study a non-active interven-
tion (a movie) control group.
The overall effect of the interventions on the level of depressive symptoms was
g = 0.29 (95 % CI: 0.150.43), with almost no heterogeneity (I2 = 7; 95 % CI: 073).
This effect size can be interpreted as small to moderate, and it corresponds to an
NNT of 6.17.
There were some indications for publication bias. Duval and Tweedies trim and fill
procedure indicated that the mean effect would drop from g = 0.29 to g = 0.22 (95 % CI:
0.070.38; number of imputed studies = 2) after adjustment for publication bias.
Only two studies examined the effects of indicated prevention on the incidence
of major depressive episodes [10, 28]. However, the relative risk (RR) of developing
a depressive episode at follow-up was RR = 0.37 (95 % CI: 0.150.91; p = 0.03),
indicating that people who received the preventive intervention had 63 % less
chance of developing a depressive episode than people in the control group.
Heterogeneity (I2) was zero. We also calculated the NNT (as the inverse of the risk
difference). The NNT of indicated prevention compared with the control groups
was 10.53 (95 % CI: 5.7857.80; p = 0.02).
Because of the small number of studies we did not conduct any additional
analyses.
7.6 Discussion
Although much research has focused on prevention of depressive disorders in

children and adolescents, a growing number of studies have examined the possibili-
ties to prevent depression in older adults. Furthermore, several manuals for
Table 7.1 Selected characteristics of studies examining the effects of interventions for indicated prevention in older adults
Recruitment Target group Definition of minD Conditions N Intervention For Nse FU TR PR Quala Country
[8] Community Older adults Self-reported 1. CBT 31 Coping with Grp 10 + + NL
(55+) depressive symptoms; 2. WL 36 depression
no MDD course (CWD)
[10] Screening Nursing home GDS E 9; no MDD 1. CBT 20 Coping with Grp 13 3, 6 + + + CA
residents 2. CAU 23 stress course
(CWD)
[22] Through Medically ill GDS 11 at two 1. IPC 31 Interpersonal Ind 10 + + US
medical older adults occasions 2. CAU 38 counseling
centers (60+)
[25] Community Older adults CES-D 5; no MDD 1. Life review 83 Life review Grp 12 + ++++ NL
(50 years) 2. Control 88 therapy
[9] Community Older adults EDS 12, no MDD 1. internet CBT 102 Coping with Grp 10 + ++++ NL
(5075 years) 2. Group CBT 99 depression
3. Waiting list 100 course (CWD)
[28] Screening in Older primary CES-D 16; no MDD 1. Stepped-care 86 Stepped-care Ind 6, 12, 24 + ++++ NL
primary care care patients 2. CAU 84 protocol
[20] Through Older adults Minor depression (3 1. PST 50 Problem-solving Ind 6 + ++++ US
primary care of 9 MDD symptoms, 2. Placebo 57 therapy
4 weeks); no MDD
a
In this column a positive (+), or negative () sign is given for four quality criteria, respectively: allocation sequence; concealment of allocation to conditions; blinding of assessors;
and intention-to-treat analyses.
evidence-based preventive interventions are now available, and prevention of

depression has been established quite well. Seven randomized controlled trials have
shown positive effects of these interventions on the level of depressive symptoms in
older adults with subclinical depression, and there is some preliminary evidence
that these interventions may also reduce the incidence of depressive disorders at 12
years follow-up.
There are several challenges for preventive interventions in older adults [38].
One important issue is to identify the optimal target groups for preventive interven-
tions. Both indicated and selective preventive have been found to be effective in the
prevention of depressive disorders. However, both types of prevention are aimed at
high-risk groups and all known risk indicators of depressive disorders have the
problem that their specificity is low. This low specificity implies that most subjects
who are exposed to the risk factor do not develop the disorder and that one such risk
factor by itself is not sufficient to produce the disorder. Recently, more sophisticated
methods have been developed to identify ultra high-risk groups. These groups typi-
cally do not have only one high-risk indicators, but a combination of these factors.
Furthermore, they are as small as possible (for efficiency reasons), but are respon-
sible for the largest possible proportion of new incident cases [39, 40]. Although
these epidemiological methods have been well-developed, they have not yet been
translated into preventive intervention research. It may be possible that the use of
biosignature data (e.g., inflammatory cytokines; [42]) may improve the identifica-
tion of which persons with subsyndromal symptoms and may benefit from indicated
preventive interventions.
Another challenge is to improve access to preventive services. Although preven-
tion of depression is effective, the interest to participate in these interventions is not
very high. In the Netherlands, about 80 % of the Dutch adult population has direct
access to free (or almost free) preventive services for depression (the CWD).
However, on a national level each year only a few thousand people with subthreshold
depression participate in these courses. Although these interventions are valuable for
these participants, about 750,000 people are estimated to have subclinical depression
and the few thousand participants are less than 1 % of this group. A challenge for the
future is to increase the number of people who participate in these services. Several
experiments are currently being conducted to increase the number of participants,
including prevention through the internet, and other organizational models in which
preventive services are better integrated into routine primary care.
The final challenge we want to mention is to improve the effectiveness of our
interventions. Although preventive interventions have been found to be effective,
their efficiency should be improved. In this chapter, we found an NNT of 10.53.
This means that 11 older people with subclinical depression have to participate in a
preventive intervention to prevent the onset of one new case. This is definitely a clini-
cally relevant effect, considering the impact depression has on the quality of life of
the patient and his or her relatives. But it would be even better if we could further
improve the effects of the interventions. In a recent trial, we found that a stepped-care
intervention was considerably more effective in older adults with subthreshold
depression, with a reduction of the incidence of 50 % [28].
We can conclude that several indicated preventive interventions are available for
older adults, and that the research on these interventions has found positive effects
both on decreasing depressive symptomatology and on reducing the incidence of
depressive disorders.
This work was supported in part by the NIMH grant P30 MH90333 and the UPMC Endowment in
Geriatric Psychiatry.
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Selective and Universal Prevention
of Late-Life Depression 8
Olivia I. Okereke
Abstract
This chapter provides illustrations of the Institute of Medicine framework of
prevention as it pertains to selective and universal prevention of late-life depres-
sion. Examples of completed randomized trials for late-life depression prevention,
using each approach, are described in detail. Advantages and limitations involved
in applying each of these prevention modalities for late-life depression are dis-
cussed. Accompanying tables provide concept definitions and summarize key find-
ings from the research literature to date. Finally, attention is given to promising
future directions for both selective and universal prevention strategies, and particu-
lar emphasis is placed on possible means to reduce the practical barriers to testing
and implementing universal prevention approaches in late-life depression.
Keywords
Selective prevention Universal prevention Randomization Clinical trial
Randomized controlled trial Institute of Medicine Geriatric Depressive
disorders Vitamins Psychotherapy
8.1 Overview and Definitions of Selective

and Universal Prevention
As previewed in the preceding chapter of this volume, three modes of prevention

of mental disorders have been described: indicated, selective, and universal.
The Institute of Medicine (IOM) defined them as follows: (1) indicated prevention
refers to interventions undertaken at the level of individuals with symptoms/early

181 Longwood Avenue, 3rd floor, Boston, MA 02115, USA

114 O.I. Okereke
Table 8.1 Overview of the Institute of Medicine framework for prevention, applied to late-life
depression
Mode of prevention Target for prevention
Indicated Older persons with subthreshold depressive symptoms, but not
meeting clinical criteria for depression
Selective Older persons with selective factors associated with particularly
heightened risk of depression, e.g., presence of physical/functional
disability, medical illness/comorbidity, etc.
Universal Older adults, regardless of presence of symptoms or risk status
indicators of illness but without the full clinical syndrome; (2) selective prevention
pertains to approaches applied among persons at increased risk of illness, based on
risk factors (e.g., sociodemographic, lifestyle/behavioral, health/medical, etc.),
regardless of whether symptoms are present; (3) universal prevention involves
interventions that can be applied among the entire population at risk, without regard
to presence of symptoms or risk factors [1] (Table 8.1).
Thus, compared to other formulations of prevention, such as primary, secondary,
or tertiaryin which interventions are targeted at the level of disease/stage of dis-
easethe IOM conceptual framework involves interventions that are targeted at the
level of risk in the population [2]. This chapter will follow the description of indi-
cated prevention in the preceding chapter by providing illustrations of approaches
for selective and universal prevention of late-life depression.
8.2 Selective Prevention in Late-Life Depression
Selective prevention necessarily implies an initial step of risk factor evaluation,

such that persons at heightened risk can be identified. Thus, important potential
barriers to selective prevention include (1) lack of provider awareness of key risk
factors for late-life depression, (2) need for tools for assessment of risk indicators,
and (3) inadequate evidence base regarding which specific preventive interventions
are likely to be successful among people with specific risk factors. In addition, find-
ing ways to integrate knowledge of risk factor assessment and selective prevention
approaches into routine primary care practice for older adults is another important
challenge. Nevertheless, recent literature has advanced the field by providing
considerable guidance regarding key risk factors. For example, Schoevers et al. [3]
examined numerous selective prevention risk indicators; they included demographic
factors (gender, age, living status (alone vs. with others), spousal loss) and health/
medical (disability, presence of medical illness, trouble sleeping, cognitive
impairment (measured via Mini-Mental State Exam)). The authors reported pres-
ence of physical or functional limitation/disability, spousal loss, and medical illness
as substantial potential contributors to total risk of late-life depression; incorpo-
rating knowledge of living status and female gender improved computation of
risk, particularly when all of the above were also considered in the context of
8 Selective and Universal Prevention 115
presence/absence of subsyndromal depression. Moreover, selective prevention studies

have an important numbers advantagesimilar to that of indicated prevention
trials: the relatively high incidence of depression among persons with key risk
markers enables investigator to test interventions with strong statistical power, even
with somewhat modest sample sizes. This fact was illustrated by Schoevers and col-
leagues [3], in which the authors were able to account for nearly 50 % of total risk
of late-life depression with consideration of only a handful of factors. Indeed,
research, largely generated by groups in the Netherlands and the USA, has identi-
fied that selective prevention may be one of the most efficient approaches to late-life
depression prevention, as they have estimated that targeting persons at high risk for
depressionbased on risk markers such as medical comorbidity, low social sup-
port, or physical/functional disabilitycan yield theoretical numbers needed to
treat (NNTs) of approximately 57 in primary care settings [47].
Incorporating knowledge of potential late-life depression risk factors, as described
above, authors of several recent studies have successfully implemented selective pre-
vention in clinical trials. As shown in Table 8.2, such trials have been undertaken in
diverse samples of older persons, in diverse settings, and with a broad range of inter-
ventions (note: only trials of 3 months of treatment and/or follow-up are shown).
Numerous selective prevention randomized trials focused on older adults with
major medical illness or comorbidity. For example, Rovner et al. [8] conducted a
trial among 206 older patients at an eye care institution; importantly, all of the
patients had already been diagnosed with AMD (age-related macular degeneration)
and were newly diagnosed with disease in the second eyethus, patients were at
heightened threat of substantial visual loss. Patients were randomly assigned to
receive either problem-solving therapy (PST) or usual care. At 2 months of follow-
up, participants in the PST-assigned group had a lower odds of developing a depres-
sive disorder than control/usual care participants (odds ratio [OR] = 0.39, 95 %
confidence interval [CI] = 0.170.92, p = 0.03). After a total of 6 months of follow-up,
however, most of the earlier observed benefits had diminished, though PST-treated
participants were less likely to suffer from persistent depression (2(1,3) = 8.46;
p = 0.04); thus, the authors suggested that booster sessions of PST may be required
to yield more sustained preventive effects. In another successful example of selec-
tive prevention among medically ill older persons, Robinson et al. [9] conducted a
selective prevention RCT among depression-free elderly patients recovering from
recent stroke and used a three-group design: escitalopram, PST, or placebo control.
Those receiving escitalopram had about one-quarter the incidence of major depres-
sion at 1-year follow-up, compared to those receiving placebo; patients who received
PST had an intermediate outcome not significantly different from the placebo group
in the intent-to-treat analyses [9]. However, by 6 months after discontinuation of the
preventive intervention, the treatment group that had previously received escitalo-
pram had greater levels of depressive symptoms than either of the other study groups
[10]; thus, it is clear that further research is needed to identify the optimal means for
achieving more enduring benefits of selective preventive interventions. In another
RCT of older adults with a recent stroke or transient ischemic attack, Almeida et al.
[11] reported that patients given folic acid (2 mg/day), vitamin B6 (25 mg/day), and
116
Table 8.2 Randomized trials of selective prevention of late-life depression

Intervention/assessment Depression
Study/authors Year Modality Study population N tool evaluation tools Author findings
Salminen 2005 Selective Coronary heart 222 Health advocacy and Zung Men with moderate or greater depressive
et al. (Lieto, disease patients aged counseling program Depression symptoms at baseline and who received
Finland) 65 Scale the intervention reported fewer depressive
symptoms than those in the control group
at follow-up. These differences were not
found among women in the study
Rovner et al. 2007 Selective Patients of clinics of 206 Problem-solving therapy SADS, HDRS At 2 months of follow-up, subjects who
(Philadelphia, Wills Eye Hospital received PST had a lower odds of
PA) with AMD (aged developing a depressive disorder than
65) control subjects (OR = 0.39, 95 %
CI = 0.170.92, p = 0.03). After 6 months
of follow-up, however, there was no
association between treatment group and
incident depressive disorders
Almeida et al. 2010 Selective Survivors of stroke 273 Daily folic acid (2 mg), MINI After a mean 7.1 years of follow-up,
(Australia) (mean vitamin B6 (25 mg), and random assignment to B vitamins was
age = 63 years); vitamin B12 (0.5 mg) associated with a lower hazard of
depression prevention DSM-IV MDD compared with placebo
ancillary sub-study in (18.4 % vs. 23.3 %, adjusted hazard ratio
the VITATOPS trial [HR] = 0.48, 95 % confidence interval
[CI] = 0.310.76)
O.I. Okereke
8
Robinson 2008 Selective Mid-life and older 176 Escitalopram, PST SCID After 1 year of follow-up, patients who
et al. (Iowa adults (mean received placebo were significantly more
City, IA) age = 64 years) within likely to develop depression than
3 months of acute individuals who received escitalopram
stroke (22.4 % vs. 8.5 %, adjusted HR = 4.5,
95 % CI = 2.48.2) and also more likely
than individuals who received PST
(11.9 %, adjusted HR = 2.2, 95 %
CI = 1.43.5). Participants who received
PST did not significantly differ from the
placebo group in the intent-to-treat
analyses, however
Burns et al. 2007 Selective Adults aged 60 who 172 Psychological treatment GDS-15, HADS Participants receiving the psychological
(Manchester, recently underwent intervention were not significantly less
UK) surgery for hip likely to have incident depression than

fracture those in the control group (OR = 0.40,
95 % CI = 0.121.30, p = 0.15)
Shyu et al. 2013 Selective Patients aged 60 299 Comprehensive care GDS-15 The comprehensive care group was less
(Taoyuan, with hip fracture program vs. simple likely to be at risk for depression than
Taiwan) interdisciplinary care the comparison group (OR = 0.48, 95 %
CI = 0.280.83, p < 0.01)
Phillips et al. 2000 Selective African Americans 202 Education/pain CES-D At 2 years of follow-up, participants in
(New York, aged 6775 years management program the intervention group were found to
NY) with arthritis and have significantly fewer symptoms of
chronic pain depression than those in the control
group (p < 0.01)
Rybarczyk 2001 Selective HMO-referred older 243 Mind/body wellness CES-D No significant difference was found in
et al. patients with chronic course, cognitive- the CES-D scores of the intervention vs.
(Chicago, IL) illness behavioral treatment control groups at 1-year follow-up. The
intervention was effective at reducing
sleep difficulties but not depression or
anxiety symptoms
117
(continued)
118

Wang et al. 2009 Selective Adults with knee 40 60 min session of tai chi CES-D The tai chi group had a significantly
(Boston, MA) osteoarthritis (mean 2/week lower mean CES-D score, after 12 weeks
age = 65 years) of follow-up, compared to the attention
control group (mean difference = 6.70
[95 % CI 11.63, 1.77; p = 0.009])
Saito et al. 2012 Selective Adults aged 65 who 63 Social isolation GDS Although the intervention was effective
(Tokyo, recently relocated to prevention program at reducing loneliness levels on a
Japan) suburban Tokyo loneliness scale, no significant
association was found between the
program and risk of depression
Ukawa et al. 2012 Selective Adults aged 65 252 Functioning Improvement Zung There was no significant difference in
(Hokkaido, living at home in rural Tool (FIT) home visit Depression the mean depression scores of the FIT
Japan) Japan and receiving program Scale intervention and control groups at
preventive services or follow-up
participating in a
long-term care
prevention project
DeChamps 2010 Selective Adults aged 65 in 49 Individualized Cognition- GDS-15 There was a significant difference in
et al. long-term care Action program GDS scores between the intervention
(Bordeaux, and control groups after 12 weeks, with
France) the intervention group having a lower
mean score (effect size = 0.37)
Justine et al. 2010 Selective Adults aged 60, 43 Multicomponent exercise CES-D After 12 weeks of the exercise program,
(Ehsan, residents of a shelter program the intervention group reported improved
Malaysia) home (i.e., quality of life when compared to the
institutional setting) control group but not lower levels of
in Malaysia depression
O.I. Okereke
8
Konnert et al. 2009 Selective Nursing home 64 Cognitive-behavioral GDS, CES-D Scores were evaluated at baseline, 3
(Calgary, residents aged 60 treatment program months, and 6 months. The mean GDS
Alberta, scores of the two groups were
Canada) significantly different over 6 months of
follow-up, with the intervention group
scores being lower (t = 3.45, p < 0.001).
There was no difference found in the
CES-D scores of the two groups at
3-months follow-up
Haight et al. 1998 Selective Newly relocated 256 Life-review course BDI After 6 weeks of receiving the
(Charleston, nursing home intervention, the experimental group was
SC) residents aged 60 significantly less likely to have
developed clinical depression than the
control group (p < 0.05). A significant
difference in the depression scores of the

two groups was also observed after 1
year of follow-up
Andreeva 2012 Selective Cardiovascular 2,000 0.56 mg GDS Following an average 5 years of
et al. (France) disease/event 5-methyltetrahydrofolate, treatment, B vitamin supplementation
survivors, aged 3 mg vitamin B6 and did not have a significant effect on
4580 in the 0.02 mg vitamin B12/day; depressive symptoms (OR = 0.91, 95 %
SU.FOL.OM3 trial 600 mg EPA + DHA/day; CI = 0.75, 1.11). N-3 PUFA
(mean age = 61 years, or both supplementation was associated with a
SD = 9 years) greater risk of depressive symptoms
compared to placebo in men only
(OR = 1.28, 95 % CI = 1.03, 1.61)
Giltay et al. 2011 Selective Hospital patients 4,116 400 mg EPA + DHA/day, GDS-15 There were no significant differences
(the aged 6080 who had 2 g ALA/day, or both found between any of the three groups
Netherlands) experienced an MI and placebo regarding levels of
depressive symptoms after 40 months (p
for EPA-DHA vs. placebo = 0.41; mean
difference = 0.048 0.044)
119
(continued)
120
Sinn et al. 2012 Selective Adults 65 with mild 50 EPA-rich supplement GDS-15 After 6 months of follow-up, the mean
(Australia) cognitive impairment (1.67 g EPA + 0.16 g GDS-15 scores in the EPA and DHA
DHA/day) or DHA-rich groups significantly decreased over the
supplement (1.55 g study period compared to that of the
DHA + 0.40 g EPA/day) control group (p = 0.04 and p = 0.01,
respectively)
O.I. Okereke
vitamin B12 (0.5 mg/day) had a significantly lower risk of developing major depression
than patients on placebo. In yet another study involving persons with cardiovascular
disease, Salminen and colleagues [12] conducted a trial of health advocacy and
counseling vs. usual care among 222 patients with coronary heart disease, aged 65
years and above, in Finland. The intervention consisted of a program of health advo-
cacy, counseling, and activation intended to increase participants knowledge about
CHD, social activities, role participation, support, and exercise. The investigators
found that depressive symptoms tended to decrease in intervention group but to
increase in control group among those men with moderate or above depressive
symptoms at baseline; however, no similar changes were found among the women
in the study.
Several of the studies summarized in Table 8.2 all focused on older participants
with another major risk factor: physical impairments (in this case, due to musculo-
skeletal problems). Burns et al. [13] described findings from a selective prevention
trial among 172 adults aged 60 years who had recently undergone surgery for hip
fracture. Participants received either usual care or the psychological intervention
(an evidence-based psychiatric nurse-led care intervention with elements including
compliance enhancement, assistance with referrals to other professionals, advising
on other services (e.g., social care), education about depression, and problem-
solving). The intervention group participants, however, were not significantly less
likely to have incident depression than those in the control group (OR = 0.40, 95 %
CI = 0.121.30, p = 0.15), although the effect was noticeably in the direction of ben-
efit. In a similar trial, Shyu and co-workers [14] treated 299 older adults aged 60
years and above, with hip fracture, with a comprehensive interdisciplinary care
intervention vs. simple interdisciplinary care. Participants assigned to comprehen-
sive care (including interdisciplinary care, nutrition consultation support, depres-
sion care management, and fall prevention) were less likely to be at risk of depression
(OR = 0.48, 95 % CI = 0.280.83; p < 0.01) compared to those who received simple
interdisciplinary care. In addition, Wang et al. [15] conducted a smaller-scale trial
using the more novel intervention of tai chi (vs. attention control) among 40 older
adults with knee osteoarthritis (mean age = 65 years). The investigators found that
after 12 weeks of follow-up, participants in the tai chi group had significantly lower
mean CES-D scores, compared to the attention control group (mean differ-
ence = 6.70 [95 % CI 11.63, 1.77; p = 0.009]). Finally, Phillips [16] conducted a
trial among 202 older African-American adults (aged 6775 years) with arthritis
and chronic pain; the active experimental intervention was an education/pain man-
agement program. At 2 years of follow-up, those participants in the intervention
group had significantly lower symptoms of depression on the CES-D than those in
the control group (p < 0.01). In contrast with the abovementioned studies, which
largely supported benefits of selective preventive interventions among older persons
with medical illness, Rybarczyk et al. [17] did not observe significant differences in
depression outcomes: in a study of 243 older patients with chronic illness, experi-
mental intervention (mind/body wellness course, cognitive-behavioral treatment)
yielded no significant differences in CES-D scores at 1-year follow-up compared to
control, although the intervention appeared effective at reducing sleep difficulties.
122 O.I. Okereke
Other selective prevention trials in late-life depression have focused on social or

demographic risk factors as opposed to health factors. Two recent studies based in
Japan focused on socially isolated older adults. Saito et al. [18] conducted a trial of a
social isolation preventive intervention program among adults aged 65 years who
recently relocated to suburban Tokyo (n = 63); although the intervention was effective
at reducing loneliness as measured by a loneliness scale, there were no significant
associations found between the intervention and depression, measured using the
GDS. Similarly, Ukawa and colleagues [19] examined benefits of a Functioning
Improvement Tool (FIT) home visit program among 252 home-dwelling older
persons living in rural Japan and receiving preventive services or participating in a
long-term care prevention project; again, there was no significant difference in mean
depression scores of the intervention and control groups at follow-up.
A number of selective prevention trials have aimed interventions at older people
living in institutional settings. Justine et al. [20] conducted a study using a multifac-
eted exercise intervention among 43 older adults, aged 60 years, who were resi-
dents of a shelter home (i.e., an institutional setting) in Malaysia. After 12 weeks of
the exercise program, the intervention group reported improved quality of life when
compared with the control group, but not lower levels of depression as measured by
the CES-D. In another study based in an institutional setting, Konnert et al. [21]
administered a CBT program among 64 older nursing home residents; evaluation
tools included a diagnostic evaluation using the SCID (clinical depression was an
exclusion criterion at baseline) as well as the GDS and the CES-D. Both groups
were assessed on measures of depression before treatment, after treatment, and at
3- and 6-month follow-up points. Compared with the treatment as usual (TAU) con-
trol group, nursing home residents receiving the intervention (a CBT coping with
stress intervention) showed improvement on the GDS over the 6-month follow-up
on the GDS; for example, average scores on the GDS went from 14.0 to 9.4 points
in the CBT group over the course of treatment and follow-up vs. from 13.4 to 12.3
for the TAU group over the same period. However, interestingly, results on the
CES-D scale at 3 months were not statistically significant. Overall, however, the
results from the Konnert and colleagues study suggested that brief, group-based
CBT intervention can reduce depressive symptoms among nursing home residents
at risk for depression. Haight et al. [22] also reported benefits of a selective preven-
tive intervention in the nursing home setting. The investigators conducted an inter-
vention of a life-review course among 256 newly relocated nursing home residents
aged 60 years; the outcome was the BDI. After 6 weeks of receiving the interven-
tion, the experimental group was significantly less likely to have developed clinical
depression than the control group (p < 0.05), and a significant difference in the
depression scores of the two groups was also observed after 1 year of follow-up.
Similarly, DeChamps and colleagues [23] implemented an Individualized Cognition-
Action program for late-life depression prevention among 49 adults aged 65 years
and residing in long-term care; the outcome variable was the GDS-15. The authors
found a significant difference in GDS scores between the intervention and control
groups after 12 weeks, with the intervention group having a lower mean score
(effect size = 0.37).
An increasingly popular treatment agent in late-life depression selective prevention

trials are vitamin and nutritional supplements, and several major trials of such
agents are summarized in Table 8.2 as well. For example, as noted above, Almeida
et al. [11] reported strong benefits for depression prevention in the high-risk group
of stroke survivors. Interestingly, however, in a large sample of 2,000 cardiovascular
disease survivors, Andreeva and colleagues, in an investigation from the SU.FOL.
OM3 trial [24] involving adults aged 4580 years (mean age >60 years) receiving
daily supplements of folate and vitamins B6 and B12 for 5 years, did not observe any
association between supplementation and depressive symptoms among an appar-
ently higher-risk group of older persons. Similarly, in another large-scale RCT,
Giltay et al. [25] treated 4,116 hospital patients aged 6080 years who had experi-
enced a myocardial infarction (MI) with 400 mg EPA + DHA/day, 2 g ALA/day,
both, or placebo; the outcome was the GDS-15. After the 40-month study period,
no significant differences were found between any of the three groups and placebo
in levels of depressive symptoms. Yet, in a smaller-scale (n = 50) study using nutri-
tional supplements among older persons at risk for depression due to cognitive impair-
ment, benefits were observed using an EPA-rich supplement (1.67 g EPA + 0.16 g
DHA/day) or DHA-rich supplement (1.55 g DHA + 0.40 g EPA/day): after 6 months
of follow-up, the mean GDS-15 scores in the EPA and DHA active treatment groups
significantly decreased compared to those scores in the control group (p = 0.04 and
p = 0.01, respectively) [26]. Therefore, some inconsistencies remain in the findings
regarding observed late-life depression outcomes in selective prevention studies
using vitamin/nutrient interventions, and further researchperhaps incorporating
biomarkers, genetics, or other means of classificationmay shed light on how these
agents work and for whom.
Thus, compared to the findings from selective prevention trials targeting older
persons with general health/medical problems, the abovementioned trials targeting
older persons based on sociodemographic risk factors have been more mixed and did
not reveal as consistent a pattern of benefits for selective prevention of depression.
However, a caveat in interpreting these findings is that the risk indicators of being at
risk for isolation/loneliness or living in an institutional setting are not among those
that have been found to be the strongest contributors to risk of late-life depression;
indeed, given earlier work by Schoevers, Smit, and others [36], it would not be
surprising that selective interventions targeting those with physical impairment and/or
medical illness would be more likely to show effects.
8.3 Universal Prevention in Late-Life Depression
Compared with the current corpus of studies on selective prevention of late-life

depression, relatively fewer trials have been conducted utilizing the approach of
universal prevention. This may primarily be the result of a major intrinsic limitation
for such trials of low-incidence disorders such as depression: low statistical
power and consequent sample size requirements. In a detailed treatment of the
subject, Cuijpers [27] examined that problem comprehensively and quantitatively.
124 O.I. Okereke
As Cuijpers explains, low-incidence conditions (which tend to be the norm for

psychiatric disorders) translate to lower numbers of new cases that can be observed
during follow-up; this will limit investigators power to illustrate that an interven-
tion yielded significant advantages compared to the control arm, in terms of cases
prevented. For example, in late-life depression estimates of true incidence are on the
order of 1 or 2 % (e.g., 1020 cases per 1,000 person-years of follow-up). However,
as Cuijpers calculations illustrated, several thousandor even tens of thousands
ofparticipants would be required per treatment arm in order to have adequate
statistical power to show even modest effects (e.g., on the order of 1530 % relative
risk reductions). Thus, true universal prevention designs are generally out of reach,
as such necessarily large-sample trials in late-life depression would be impractical
or prohibitively expensive to undertake. By contrast, in indicated and selective pre-
vention designswhere the expected number of cases is considerably higher due to
the risk profiles of the participantsstatistical power and sample size requirements
are more favorable.
Another important intrinsic barrier for universal prevention is the availability, of
lack thereof, of an appropriate intervention. Because the universal paradigm would
involve exposing everyone to the intervention, regardless of baseline risk status, it is
first and foremost ethically imperative that the intervention be safe as well as mini-
mally intrusive and burdensome for participants. Second, there should already be a
credible evidence base for likely efficacy of the interventionsuch as strong bio-
logic plausibly of benefit of pharmacologic interventions or prior evidence in other
settings of potential benefits of non-pharmacologic interventions. Third, in order to
meet any expectation of wide-scale use, the intervention would need to have high
acceptability: that is, the intervention must be something that the average person
would tend to find appealing or acceptable and would, thus, be willing to undertake.
Finally, the intervention would need to be very low cost in order to have any chance
of cost-effectiveness if applied universally. Thus, the four factors enumerated
abovesafety, evidence for efficacy, acceptability, low costwere identified and
coined by Okereke and colleagues [2] as the SEAL standard for universal
prevention.
Despite the intrinsic challenges, several studies have examined universal prevention
of late-life depression. Table 8.3 provides a summary (note: only trials of 3 months of
treatment and/or follow-up are shown).
Perhaps because such interventions are most likely to meet the SEAL require-
ment for universal prevention, as described by Okereke and colleagues [2], many of
the existing late-life depression universal prevention trials have employed vitamin/
nutrient agents. One such early trial was undertaken to examine depression
prevention with folic acid/B vitamins. In contrast with the Almeida et al. study
addressing persons at high risk due to cerebrovascular disease, however, Walker and
coinvestigators did not observe significant differences by treatment group in a larger
RCT among older adults in the general population [28]. Two other RCTs [29,30]
that had enrolled older participants without clinically significant depression at base-
line both found that daily folate, vitamin B6, and vitamin B12 supplementation did
not reduce incidence of late-life depression compared with placebo. A study by
8
Table 8.3 Randomized trials of universal prevention of late-life depression

Intervention/ Depression
Study/authors Year Modality Study population N assessment tool evaluation tools Author findings
Muoz et al. 1995 Universal Older adults in general 150 CBT DIS, CES-D, The experimental intervention group
(San Francisco, outpatient primary care BDI, other (CBT) reported significantly greater
CA) measures reduction in depression levels compared
to care as usual, but no significant
differences in MDD incidence were
observed in the 1-year trial
Bertone- 2012 Universal Postmenopausal 2,263 1,000 mg elemental Burnham scale, No association was found between
Johnson et al. women (aged 5079) calcium and 400 IU antidepressant vitamin D/calcium supplementation and
(USA) in the Womens Health vitamin D3/day use depressive symptoms after 2 years of
Initiative (WHI) follow-up (OR = 1.16, 95 %
Calcium and Vitamin CI = 0.861.56)

D (CaD) Trial
Almeida et al. 2012 Universal Primary care patients 21,762; Educational PHQ Those in the intervention group did not
(Perth, 60 and their GPs 373 GPs intervention have significantly lower odds of incident
Australia) depression, though they were
significantly less likely to report
self-harm behavior. Post hoc analyses
showed that the relative effect of the
intervention on depression was not
significant (OR = 0.93, 95 % CI
0.831.03), but its impact on self-harm
behavior over 24 months was (OR = 0.80,
95 % CI 0.680.94)
Walker et al. 2010 Universal Community-dwelling 909 400 g/day folic PHQ-9 After 24 months, the change in PHQ-9
(Australia) adults aged 6074 acid and 100 g/ scores in the supplement group was not
day vitamin B12 significantly different than that of the
placebo group (p = 0.476)
(continued)
125
126
Intervention/ Depression
Study/authors Year Modality Study population N assessment tool evaluation tools Author findings
Ford et al. 2008 Universal Men aged 75 without 299 2 mg folic acid, BDI Although participants who received the
(Perth, clinically significant 25 mg vitamin B6, intervention had a 24 % lower risk of
Australia) depression and 400 g vitamin developing depression than those in the
B12/day placebo group, the difference was not
significant (95 % CI = 0.682.28). B
vitamin treatment did not prevent or
reduce depressive symptoms compared
with placebo (p = 0.284)
Dumville et al. 2006 Universal Female primary care 2,117 800 IU vitamin D/ Mental Average MCS scores of the supplement
(UK) patients 70 day Component and placebo groups were not significantly
Score of SF-12 different after 6 months of follow-up,
adjusting for baseline scores (p = 0.262)
Van de Rest 2008 Universal Community-dwelling 302 1,800 mg CES-D, After 26 weeks of follow-up, there were
et al. adults 65 without EPA + DHA/day or GDS-15, other no significant differences between the
(Wageningen, depression 400 mg measures mean changes in CES-D, GDS-15, or
the EPA + DHA/day other measures of the placebo group and
Netherlands) those of the fish oil groups
O.I. Okereke
8
Snchez- 2013 Universal Adults aged 5580 in 3,923 Mediterranean diet Self-reported After 3+ years of follow-up, participants
Villegas et al. the PREDIMED trial supplemented with depression in the Mediterranean diet + nuts group
(Spain) with CVD risk factors nuts or olive oil diagnosis or had a lower risk of developing depression
but without CVD (vs. low-fat diet antidepressant than those in the low-fat/control group,
control) use though the association was not
statistically significant (HR = 0.78, 95 %
CI = 0.551.10). When restricted to
participants with type II diabetes, the
association between Mediterranean
diet + nuts and incident depression was
significant (HR = 0.59, 95 %
CI = 0.360.98)
Okereke et al. 2014 Universal Mid-life and older 4,331 2.5 mg folic acid, Self-reported After a mean 7 years of follow-up, there
(USA) women (mean age = 64 50 mg vitamin B6, clinician was no difference in risk of incident
years) in the Womens and 1 mg vitamin diagnosis of depression between the B vitamin and
Antioxidant and Folic B12/day depression or placebo groups (RR = 1.02, 95 %
Acid Cardiovascular clinically CI = 0.861.21, p = 0.81)
Study (WAFACS) trial significant
depressive
symptoms on
the Mental
Health Index
127
128 O.I. Okereke
Ford et al. [29] involved 299 men aged 75 years and older who received 2 mg folic
acid, 25 mg vitamin B6, and 400 g vitamin B12 daily for 24 months; the study by
Okereke and colleagues [30] involved a large sample (n = 4,331) of older women
who were administered daily a high-dose folic acid/B vitamin combination pill
(2.5 mg folic acid, 50 mg vitamin B6, and 1 mg vitamin B12/day) over a lengthy
treatment period (mean treatment duration = 7 years) in the Womens Antioxidant
and Folic Acid Cardiovascular Study (WAFACS). Thus, it would appear that B vita-
mins have limited utility in late-life depression in universal prevention paradigms.
However, as cautioned by Okereke et al. [30], it is notable thatbearing in mind the
daunting statistical power problem described by Cuijpers [27]even a trial with a
sample size as large as that in the WAFACS may not be adequate to detect more than
moderate or larger effects (e.g., >30 % relative risk reductions) under conditions of
universal prevention.
Other universal prevention trials have examined the effects of non-B vitamin sup-
plements. A sub-study [31] conducted within the Womens Health Initiative Calcium
and Vitamin D (WHI-CaD) Trial found that postmenopausal women (all aged 50+
years) who received daily supplements of 1,000 mg elemental calcium and 400 IU
vitamin D3 for a mean treatment period of 2 years were not less likely to experience
meaningful depressive symptoms at follow-up than the women who were taking pla-
cebo. Similarly, the results from another RCT [32] of vitamin D showed no difference
between the SF-12 (Medical Outcomes Study-Short Form-12) Mental Component
scores among older women receiving 800 IU vitamin D daily vs. those of the placebo
group, after 6 months of treatment.
Another popular area of nutritional intervention involves healthy fats and
omega-3 fatty acids. Since the data from numerous cohort studies [3335] suggested
that healthy fats, including omega-3 fatty acid, and/or Mediterranean diet intake may
play a role in preventing depression in older adults, a number of clinical trials have
recently been carried out to better examine these associations. A statistically nonsig-
nificant inverse relation was found between a Mediterranean dietary pattern interven-
tion and incident depression in the PREDIMED trial [36] (HR = 0.78, 95 % CI = 0.55,
1.10), a primary prevention RCT that included adults between the ages of 55 and 80
with cardiovascular disease risk factors but without cardiovascular disease. However,
when only participants with type II diabetes were included in the analysis, the inverse
association between following a Mediterranean diet supplemented with nuts for at
least 3 years and incident depression became significant and the estimate was strength-
ened (HR = 0.59, 95 % CI = 0.36, 0.98). By contrast, another universal prevention trial
[37]this time evaluating one of the putative key components of Mediterranean diet
(omega-3 fatty acids, in which fish and nuts are nutrient-rich)did not observe any
beneficial association. In a study among older adults (all aged over age 60 years), van
de Rest and colleagues [37] did not observe an association between omega-3 supple-
mentation and CES-D or GDS-15 scores. Overall, the available data on the effect of
omega-3 fatty acids for universal prevention of depression among older adults is
sparse and therefore inconclusive; further intervention studies that evaluate the role of
omega-3s in preventing late-life depression in universal paradigms are needed to
inform conclusions.
Finally, studies have evaluated in universal prevention settings the same kinds of
psychological and non-pharmacologic interventions that have been applied in selec-
tive prevention of late-life depression. For example, in one of the earliest examples
of depression prevention clinical trials, Muoz and colleagues [38] enrolled 150
older adults in general outpatient primary care to receive either their experimental
intervention (CBT) or care as usual. Although the authors reported significantly
greater reductions in depression levels compared to care as usual, no significant dif-
ferences in MDD incidence were observed in this 1-year trial. In one of the largest
late-life depression prevention trials to date, Almeida et al. [39] enrolled 21,762
primary care patients aged 60 years, alongside their 373 GPs, in a trial of an edu-
cational intervention. Individuals in the intervention group did not have significantly
lower odds of incident depression, as measured by the PHQ; however, they were
significantly less likely to report self-harm behavior.
8.4 Future Directions in Late-Life Depression

Prevention Trials
Overall, there are many promising results for selective prevention of late-life depression,
particularly when interventions address those with medical or physical problems.
However, questions remain about the path forward for universal prevention, which for
reasons mentioned earlier, is affected by several intrinsic barriers. Nevertheless,
barriers to universal prevention are not insurmountable. Recently, the author of this
chapter and others have undertaken an ongoing RCT called VITAL-DEP (Depression
Endpoint Prevention in the VITamin D and OmegA-3 TriaL, NCT01696435), which
represents the first example to our knowledge of a trial designed explicitly to test
simultaneously interventions for universal, selective, and indicated prevention of
depression among older adults. It is also an example of a strategy that uses nutritional
supplements, and it meets the SEAL criteria for feasibility in universal prevention [2].
Numerous aspects of the VITAL-DEP design have implications for future directions
in late-life depression prevention research and are summarized below.
VITAL-DEP is an ancillary study of the VITamin D and OmegA-3 TriaL (VITAL,
NCT01169259), which is a large simple trial of vitamin D (in the form of vitamin D3
[cholecalciferol], 2,000 IU daily) and marine omega-3 fatty acid (eicosapentaenoic
acid [EPA] + docosahexaenoic acid [DHA], 1 g daily) supplements in the primary
prevention of heart disease and cancer among 25,875 US adults (men aged 50+
years, women aged 55+ years); the mean randomized treatment period will be 5
years [40,41], but the renewed funding of the VITAL trial will now ensure that many
participants will have treatment for up to 7 years. VITAL-DEP builds upon the exist-
ing evidence base from laboratory studies, observational research, and limited clini-
cal trials that has suggested particular benefits to mood using these nutritional
agents [4255]. However, until VITAL-DEP, large-scale trials with adequate dosing
and treatment durations to test these agents for mood effects in the general popula-
tion had been lacking. VITAL-DEP utilizes a 2 2 factorial design, such that both
separate and synergistic effects may be explicitly tested for agents; specifically,
130 O.I. Okereke
participants are randomized to one of four groups (equal allocation to each group):
(1) daily vitamin D3 and fish oil, (2) daily vitamin D3 and fish oil placebo, (3) daily
vitamin D3 placebo and fish oil, and (4) daily vitamin D3 and fish oil placebos.
The primary aims of VITAL-DEP will test whether these agents reduce risk of clini-
cal depressive syndrome and yield better mood scores over time in the full cohort of
over 20,000 people; thus, as participants will be followed for occurrence of depres-
sion regardless of baseline depression or risk factor status, the primary aims repre-
sent a true test of universal prevention. Additionally, secondary aims in VITAL-DEP
address selective and indicated prevention: among a subset of over 1,000 well-
characterized participants examined at a local Clinical and Translational Science
Center, the trial will address whether vitamin D3 and fish oil can reduce depression
incidence and yield better mood scores among persons with key high-risk factors
for late-life depression, such as physical/functional disability, medical comorbidity,
or low social support, or among those with subthreshold depressive symptoms but
who do not meet DSM-IV criteria for depression. Additional objectives in VITAL-
DEP involve testing whether the agents yield benefits to those with relevant bio-
marker levels, such as low plasma vitamin D levels.
Overall, it would be advantageous for more prevention studies to involve univer-
sal prevention paradigms, as these ultimately provide the broadest coverage with
regard to protecting persons at risk for depression. However, since de novo trials of
this type are likely to be infeasible and cost-prohibitivedue, in part, to the large
sample sizes and trial infrastructure requiredan important future direction could
be the leveraging of existing large-sample RCTs, cohort studies, or large-scale pub-
lic health promotion efforts, as was possible in the case of VITAL-DEP. Another
important future direction would be to extend existing work using collaborative care
approaches into late-life selective and universal prevention. These care models have
already been found effective for management of older patients diagnosed with
depression, as illustrated by the IMPACT (Improving Mood-Promoting Access to
Collaborative Treatment) trial [56] and PROSPECT (Prevention of Suicide in
Primary Care Elderly: Collaborative Trial) [57] studies. Thus, leveraging collabora-
tive care approaches that feature primary care providers, along with an extended
network of community-based service providers and health-supporting contacts,
might provide a vehicle to test both the utility of universal depression screening as
well as preventive interventions for late-life depression.
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Health Policy and Economic Aspects
of Late-Life Depression Prevention 9
Abstract
We discuss the policy and economic implications of preventing depression
among older adults. An overview of the US and global burden of late-life depres-
sion is provided, with special attention to numbers affected, quality of life impact,
and estimated healthcare costs. Next, using both text and table illustrations, we
summarize current policies and recommendations regarding screening for
depression among older adultsas early detection activities are key elements in
developing depression prevention strategies. Finally, we discuss current evidence
from cost-benefit analysis studies of primary and secondary prevention of late-
life depression.
Keywords
Guidelines Recommendations Screening Burden of disease Depressive
disorders Geriatric Cost benefit Cost-effectiveness QALY
9.1 Overview
A significant portion of the global disease burden, measured in disability-adjusted

life years (DALYs), is attributable to major depressive disorder. According to the
World Health Organization (WHO), unipolar depressive disorders are now the third
A. Singh, M.P.H. (*)

Channing Division of Network Medicine, Brigham and Womens Hospital,
181 Longwood Ave, Boston, MA 02115, USA
e-mail: ankura.singh@channing.harvard.edu
O.I. Okereke, M.D., M.S.
Boston, MA, USA

leading cause of global disease burden and the leading cause in developed countries [1].
Depression is responsible for a considerable amount of disability worldwide, as it
is associated with impaired daily functioning and decreased well-being [2, 3]. The
economic burden of depression therefore includes the costs of reduced productivity
in the workplace in addition to the direct medical costs [4].
While studies have estimated the prevalence of unipolar depressive disorders in
community-dwelling older adults and elderly primary care patients to be about
24 % [57] and 1014 % [8], respectively, they have found that subthreshold
depression is more common in these populations. Between 9 and 20 % of elderly
persons in the community and over 30 % of those in primary care settings report
clinically relevant depressive symptoms [9, 10]. The fact that both subsyndromal
and major depression are associated with elevated healthcare costs and increased
morbidity in older populations underscores the need for policies to prevent these
mental health outcomes [8].
Several government agencies, such as the Centers for Medicare and Medicaid
Services and the Department of Veterans Affairs, currently recommend a policy of
annual screening for depression in primary care settings [11, 12]. Once individuals
who are experiencing clinically relevant depressive symptoms have been identified
during the screening process, they should be provided with the appropriate preven-
tive care [11]. In order to assess the costs and benefits of screening and possible
follow-up treatments, cost-effectiveness analyses must be carried out in RCTs that
focus on late-life depression prevention. Few of the studies in the existing literature
that involve interventions to prevent depression and/or reduce depressive symptoms
in older populations have included economic evaluations [13]. The identification of
cost-effective interventions to provide to groups at high risk for depression is an
important public health goal, as such treatments may avert or reduce a significant
amount of the disease burden.
9.2 Burden of Depression in Later Life
9.2.1 Review of Numbers Affected in the United States

and Worldwide
In 2004, the WHO reported that 65.5 million DALYs, or 4.3 % of the total global
disease burden, could be attributed to unipolar depressive disorders [14]. Late-life
unipolar depression was estimated to cause approximately 3.3 million DALYs that
year [14] and 6.1 million years lived with disability (YLD) in 2010 [15]. The burden
of depression in middle- and high-income countries was found to be particularly
large: unipolar depressive disorders caused over 5 and 8 % of the total DALYs in
middle- and high-income countries, respectively, and were the leading cause of dis-
ease burden in both of these groupings as well as in the Americas region [14]. In the
United States, the National Health and Nutrition Examination Survey (NHANES)
estimated the prevalence of current depression in the general population to be almost
8 % between 2007 and 2010 [16], and CDC surveys in 2006 and 2008 found the
9 Health Policy and Economic Aspects of Late-Life Depression Prevention 137
12-month prevalence in adults aged 18 and older to be 9 % [17]. While major

depression is less common among the elderly than it is among young and middle-
aged adults [18], clinically relevant depressive symptoms are widespread in older
populations; between 6 and 7 million Americans aged 65 and over suffer from either
minor or major depression or dysthymia [9, 19]. Since depressed older persons have
a tendency to not seek out mental health services, it is possible that they are less
likely to be diagnosed with depression than younger adults [3, 8].
9.2.2 Results from Global Burden of Disease Studies
As depression is responsible for millions of YLDs each year, the fact that some
older adults do not utilize depression care does not offset the high direct and indirect
costs of the disease [3, 15]. In the United States alone, the total economic burden of
depression was estimated to be 83.1 billion dollars in the year 2000, which was a
7 % increase from the inflation-adjusted 1990 costs [4]. The 2000 total cost estimate
was primarily made up of workplace-related costs (62 %) and direct medical costs
(31 %), with the remaining 7 % of the total costs associated with mortality from
suicide [4]. Beekman and colleagues [3] found that baseline depressive symptoms
were significantly associated with reduced daily functioning after 3 years in a cohort
of adults aged 55 and older (p < 0.05), an outcome that can translate into decreased
productivity in the workplace.
Since a considerable portion of the older population is retired from work, how-
ever, healthcare costs are more prominent contributors to the economic burden of
late-life depression [20]. A study by Katon and colleagues [8] showed that elderly
patients with either subsyndromal or major depression had significantly higher
medical costs during the previous 6 months than those without depression; total
healthcare costs were $1,045 to $1,700 greater, and total outpatient/ambulatory
costs ranged from being $763 to $979 more, on average. Depressed patients had
greater usage of health resources in every category of care examined, including
those that are not mental health-related, such as emergency department visits.
No difference in excess costs was found between patients with a DSM-IV depressive
disorder and those with depressive symptoms only, however, as mean total costs
were 51 % higher in the subthreshold depression group (95 % CI = 1.391.66) and
49 % higher in the MDD/dysthymia group (95 % CI = 1.281.72) than in the nonde-
pressed group [8]. In a similar study, the usage of various types of health services by
primary care patients in the Netherlands was assessed, and average costs were deter-
mined to be 1,403 more in depressed individuals versus control patients [21].
Study investigators once again observed that patients with depression had greater
utilization of both nonmental and mental healthcare services than controls. Cuijpers
and colleagues [22] also examined the excess costs of depression in the Netherlands,
though they took both medical and nonmedical costs into consideration in order to
calculate the total economic burden. The yearly per capita costs of major and minor
depression were $3,313 and $2,141 higher, respectively, than the annual per capita
costs of the general population. The total annual excess costs of minor depression
were calculated to be 160 million dollars per one million persons, an amount that
was not far from the estimated $192 million/year burden of major depression [22].
Overall, more studies that focus on the total economic costs of late-life depression
are needed. Currently, comprehensive data on the economic impact of the illness are
lacking for the older age group.
9.3 Depression Screening and Assessment
9.3.1 Current Policy Regarding Screening (Table 9.1)
Since depression poses a considerable burden to countries healthcare systems and

economies, many experts recommend a strategy of routine depression screening in
at-risk populations to alleviate some of the morbidity and economic costs attributed
Table 9.1 Policies regarding depression screening

Organization Policy or recommendations References
Centers for Medicare Part B covers annual depression screening of up to [12]
Medicare and 15 min in primary care settings with staff-assisted depression
Medicaid Services resources that will ensure proper diagnosis, treatment, and
follow-up
US Preventive Recommends depression screening in adults when [24]
Services Task staff-assisted depression care supports are in place to assure
Force accurate diagnosis, effective treatment, and follow-up.
When these supports are not in place, however, USPSTF
does not recommend routine screening
American College Recommends annual 15 min depression screening for adults [27]
of Physicians covered by Medicare. Suggested screening tool: PHQ
(Patient Health Questionnaire)-9 or PHQ-2
Veterans Affairs Issued joint clinical practice guideline (CPG) for the [26]
Administration management of major depressive disorder. VA/DoD
and Department definition of a CPG: recommendations for the performance
of Defense or exclusion of specific procedures or services derived
through a rigorous methodological approach that includes
determination of appropriate criteria such as effectiveness,
efficacy, population benefit, or patient satisfaction; literature
review to determine the strength of the evidence in relation to
these criteria. CPG recommends PHQ-2 and PHQ-9 as
screening tools and provides guidance for the use and
interpretation of scores
American Recommends using PHQ-2 for initial depression screening in [23]
Geriatrics Society older adults; if results are positive, a follow-up screening
with either the PHQ-9 or GDS (Geriatric Depression
Scale)-15 should be carried out
American College States that PCPs should follow USPSTF recommendations [25]
of Preventive for screening in primary care and also maintains that
Medicine depression care resources should be in place in all primary
care practices
to the disease [13, 23]. Furthermore, government agencies and professional

organizations have issued recent guidelines or recommendations pertaining to
screening of depression, particularly in the setting of primary care. Many of these
guidelines and recommendations are highly relevant to screening among older adults.
The US Preventive Services Task Force (USPSTF) endorses screening in
primary care practices where staff-assisted depression care supports to
ensure accurate diagnosis and appropriate follow-up care are present [24], and
many agencies and organizations in the United States have instituted policies
in line with this recommendation. In order for routine depression screening in
the elderly to be cost-effective, however, the appropriate follow-up measures
must be taken with those who screen positive, including a diagnostic interview
and/or referral to a mental health professional [23, 25]. For example, subse-
quent steps may include initiation of psychotherapy or antidepressant treat-
ment. Thus, one reason that the USPSTF does not recommend screening for
depression in settings where proper mental health resources do not exist is that
the evidence suggests that outcomes are unlikely to improve without effective
follow-up care [23]. The Centers for Medicare and Medicaid Services (CMS)
have mandated that annual screening for depression in primary care settings be
covered by Medicare Part B [12]. However, as per the USPSTF suggestion,
Medicare will only cover the screening when the appropriate supports for
proper diagnosis and treatment are available. These depression care resources
may include staff that can provide either case management or referrals to men-
tal health treatment, collaboration between primary care physicians and mental
health specialists, and patient education [12]. In addition, the VA and
Department of Defense jointly issued a clinical practice guideline pertaining to
management of depression in primary care; among the recommendations is the
use of screening toolsthe two-item Patient Health Questionnaire (PHQ-2)
and nine-item PHQ (PHQ-9)and the CPG documents offer providers
guidance on the interpretation of PHQ scores [26]. Depression screening is
provided for patients in Veterans Affairs (VA) Medical Centers, where elec-
tronic medical record systems have been designed to alert staff when screen-
ings should be carried out [11]. The American College of Physicians and the
American College of Preventive Medicine also support the recommendations
of the USPSTF [25, 27], and the American Geriatrics Society also recommends
the PHQ-2 for initial screening and either PHQ-9 or 15-item Geriatric
Depression Scale for follow-up screening in older adults [23].
9.3.2 Late-Life Depression Screening Tools
Several of the screening instruments that are used to detect depression in adult
patients of all ages are effective at identifying late-life depression as well. Many
validation studies found that both the 10- and 20-item Center for Epidemiologic
Studies Depression Scales (CES-D) had high sensitivity and specificity when
screening for depression in older adults [2, 28, 29]. In one study, Lyness and
colleagues [28] compared the performance of the CES-D to the GDS and confirmed
that both scales are efficient methods of detecting major depression in elderly
patients. The Geriatric Depression Scale (GDS) was developed to recognize
depression in older individuals and is a common method of screening for depres-
sion in this population [30]. While the efficacy of the GDS-30 and GDS-15 has
been demonstrated by numerous validation studies, the sensitivity and specificity
of some of the shorter versions of this scale were also found to be high [3032].
The two- and nine-item versions of the PHQ are both frequently used to screen for
depressive symptoms in primary care settings and are valid tools for detecting late-
life depression [23, 33, 34]. Other depression screening instruments that have been
used in older populations include the Hamilton Rating Scale for Depression, the
Montgomery-Asberg Depression Rating Scale, and the Cornell Scale for Depression
in Dementia [35, 36].
9.4 Examples and Cost-Effectiveness of Primary Prevention

of Late-Life Depression
9.4.1 Studies of Cost-Benefit Analysis of Treatments to Prevent

First Case or First Onset of Late-Life Depression
In order to determine which interventions to prevent and treat depression should be

provided to those who screen positive for depressive symptoms and to high-risk
populations in general, cost-effectiveness analyses must be completed for a variety
of different treatments and preventive measures. The costs and benefits of depres-
sion screening in primary care were evaluated using Markov models in two studies,
one of which included a brief psychological intervention for positive screens [13,
37]. Results from that study showed the combination of screening and psychother-
apy to be cost-effective; from the payer perspective, the incremental cost-
effectiveness ratio (ICER) was 1,403 per DALY prevented, and when the total
economic costs of depression were considered, the intervention was found to be
cost saving [13]. In the second study [37], cost-utility analyses estimated the cost of
annual depression screening in a hypothetical cohort of primary care patients to be
$192,444 per quality-adjusted life year (QALY) gained. The cost-utility ratio of
one-time screening was found to be substantially lower at $32,053 per QALY, how-
ever, indicating that it is more likely to be considered a cost-effective strategy than
the annual intervention.
Romeo and colleagues [20] evaluated a psychological intervention that was
provided to elderly patients who had recently undergone hip surgery and did not
find it to be a cost-effective option for depression prevention compared with
usual care. Participants in the intervention group received six sessions of
cognitive behavior therapy, and there was no significant difference in the num-
ber of cases of incident depression in the treatment versus control groups after
the 6-week period (p = 0.10). The cost of the CBT intervention was not signifi-
cantly different than that of usual care, but as the treatment did not prevent
depression or lead to better outcomes on the Hospital Anxiety and Depression
Scale (HADS), an economic evaluation showed that it was not a cost-effective
alternative [20].
Other preventive measures that have been analyzed for cost-effectiveness
include stepped care interventions, which may involve steps such as bibliotherapy,
life review, problem-solving treatment, and antidepressant medications [38, 39].
One study examined the costs and outcomes of a stepped care program in nursing
homes and found that after 10 months, the incidence of depression in the treatment
group was not significantly lower than that of the control group (0.09 vs. 0.17,
p > 0.05) [39]. Though average total costs were 838 higher in the intervention
group than the control group, this difference was also not significant. Economic
analyses determined that the excess cost of preventing depression in each addi-
tional patient in the stepped care group was 10,293; the high treatment costs com-
bined with lack of improvement in outcomes meant that the intervention had a very
low probability of being cost-effective. Results from an RCT in which a stepped
care program was provided to adults aged 75 and older with subthreshold depres-
sion/anxiety were more promising, as the intervention significantly reduced the
12-month incidence of depression and anxiety disorders compared with routine
care (RR = 0.49, 95 % CI: 0.240.98) [38]. Since the ICER was calculated to be
4,367 per disorder-free year, the stepped care program is more likely to be cost-
effective than usual care if decision makers are willing to pay at least 5,000 per
year of depression/anxiety averted.
The costs and benefits of an exercise intervention to prevent depression in nurs-
ing homes were evaluated by Underwood and colleagues [40], who found no
significant differences in the odds of depression or severity of depressive symp-
toms after 12 months in the active versus control groups. Since the mean differ-
ence in QALYs between the two groups was 0.0014 (95 % CI: 0.0728 to
0.0699) and costs were higher, though not significantly, in the intervention group
by 374 (95 % CI: 655 to 1,404), the exercise program was not cost-
effective. Smit and colleagues [41] asserted that preventive interventions are
likely to be cost-effective if only high-risk individuals are targeted, and while
this was not the case for the two studies mentioned above that involved nursing
home residents, it was true when the study population consisted of elderly per-
sons with subthreshold depression [3840].
9.4.2 Summary Table of Studies and Results (Table 9.2)
142
Table 9.2 Cost-benefit analyses of primary prevention of late-life depression

Study/authors Year Study design Study population N Intervention/exposure Evaluation tool Author findings
van den Berg 2011 Markov Hypothetical Opportunistic ICER, DALYs From the payer perspective, the ICER was
et al. (Bilthoven, model cohort of people screening and minimal 1,400 per DALY, and when taking
the Netherlands) diagnosed with contact psychotherapy nonmedical costs into consideration, the
subthreshold intervention was cost saving. If willing to pay
depression 20,000 per DALY avoided, the intervention
is 80 % likely to be cost-effective
Bosmans et al. 2014 RCT Residents of 185 Stepped care MINI, CES-D After 10 months of follow-up, the incidence
(Amsterdam, the elderly care prevention program of depression in the treatment group was
Netherlands) homes (mean including activity lower but not significantly different than
age = 84) with scheduling, life review, that of the control group (0.09 vs. 0.17,
subthreshold and visit to general respectively). Average total costs were 838
depression practitioner in cycles higher in the intervention group than the
of 3 months control group, though this difference was
also not significant. According to the ICER,
preventing depression in one patient via the
intervention would cost 10,293 more than
usual care. The intervention was therefore
not found to be a cost-effective alternative
to usual care
Valenstein et al. 2001 Markov Hypothetical Screening for Direct and The societal cost of annual screening versus
(Ann Arbor, MI) model cohort of depression via indirect costs, no screening was estimated to be $192,444/
40-year-old self-administered QALYs QALY. One-time screening was found to be
primary care questionnaire: either more cost-effective, at $32,053/QALY,
patients opportunistic compared to no screening. When
screening, one-time considering direct screening and treatment
screening, or screening costs only (payer perspective), the costs of
every 1, 2, 3, or 5 years annual and one-time screening versus no
screening were $225,467/QALY and
$45,298/QALY, respectively
9
Romeo et al. 2011 RCT Elderly adults 293 For patients with GDS, HADS While the cost of treatment as usual was
(London, UK) who have GDS 6, 6 weeks of 201 higher than the nurse-led intervention,
recently had hip cognitive behavior this difference was not significant. Those in
surgery therapy (CBT) for the intervention group had a lower mean
preventing depression, HADS score after 6 weeks than those in the
and for those with control group (5.7 vs. 7.8), though this
GDS > 6, 6 weeks of difference was also not significant. In the
nurse-led intervention CBT versus control group depression
for treating depression prevention study, no significant difference
in costs or depression score was found.
CBT was therefore not found to be a
cost-effective preventive intervention
Vant Veer- 2010 RCT Elderly adults 170 Stepped care MINI/ The intervention was more costly than
Tazelaar et al. 75 with preventive intervention DSM-IV, usual care (incremental cost = 532). It was
(Amsterdam, the subthreshold (including CES-D effective in significantly reducing the
Netherlands) depression or bibliotherapy, 12-month incidence of depression and
anxiety problem-solving anxiety disorders, however (RR = 0.49,
treatment, screening, 95 % CI = 0.240.98). The incremental
medication) in cycles cost-effectiveness ratio was calculated to be
of 3 months 4,367 for a disorder-free year. The stepped
care intervention appears to be a cost-
effective alternative to routine care if
willing to pay 5,000 per depression/
anxiety-free year
(continued)
Health Policy and Economic Aspects of Late-Life Depression Prevention
143
144
Smit et al. 2006 Cohort Community 2,200 Risk factors for CES-D Risk factors that significantly predicted
(Utrecht, the residents aged depression (small incident depression were chronic diseases,
Netherlands) 5585 social network, chronic depressive symptoms, functional
diseases, depressive limitations, and female sex (IRRs = 1.55,
symptoms) 2.09, 1.52, and 1.79, respectively).
Targeting those in the community who are
exposed to a combination of these risk
factors for inclusion in preventive
interventions is likely to be cost-effective,
as only a small but high-risk portion of the
population will be receiving the
intervention. As the excess costs of major/
minor depression have been computed to be
$1,045 per person per half year, the costs of
an intervention would ideally not exceed
$1,045 per avoided case
Underwood 2013 RCT Residents of 1,054 Whole-home GDS-15, 12 months after randomization, no
et al. (Coventry, elderly care intervention w/ training EQ-5D significant difference between the groups
UK) homes 65 for staff and was found in either the severity of
physiotherapist-led depressive symptoms (according to
exercise group 2/ GDS-15) or odds of being depressed. Cost
week versus depression of the exercise intervention was 374/
awareness training person and mean difference in quality-
program for staff adjusted life years was 0.0014 (95 % CI
(control) 0.0728 to 0.0699), meaning that the
exercise intervention was more costly but
not more effective than the control
intervention
9.5 Examples and Cost-Effectiveness of Secondary

Prevention of Late-Life Depression
9.5.1 Studies of Cost-Benefit Analysis of Treatments to Prevent

Recurrence of Late-Life Depression or Worsening
of Depression in People Already Diagnosed
with Depression
Depression care may have a greater probability of being cost-effective if it is focused

on reducing depressive symptoms in older adults that have screened positive for
them or others who have an elevated chance of developing depression, as only a
small but high-risk portion of the population will then be receiving the treatment [41].
Economic evaluation of a problem-solving therapy intervention in primary care
patients with mental health problems showed that PST was cost-effective, even
though the average change in HADS scores in the treatment group was not signifi-
cantly different than that of the usual care group after 9 months of follow-up (mean
difference = 0.2; 95 % CI = 3.7, 3.2) [42]. The average total costs of those receiv-
ing PST were lower, however, because of the high indirect costs of depression in the
control group. Knapp and colleagues [43] found that another psychological inter-
vention, which was provided to family caregivers of people with dementia, was
more effective at reducing depressive symptoms and not significantly more costly
than usual care. The study participants who received eight sessions of a manual-
based coping strategy program in addition to routine care had lower HADS scores
(mean difference = 1.79; 95 % CI = 3.32 to 0.33) and more QALYs (mean differ-
ence = 0.03; 95 % CI = 0.01 to 0.08) than control participants over the 8-month
follow-up period. Since the costs of the intervention were not significantly higher
than the usual treatment, there is a high likelihood of the manual-based coping strat-
egy program being cost-effective.
Economic evaluations were also carried out in several RCTs where the study par-
ticipants had been diagnosed with major depression or dysthymia and the outcomes of
interest were either reduced severity of disease or relapse rates. In the IMPACT study
[44], a care management program that included education, problem-solving treat-
ment, and medication adherence was used to treat older adults with MDD and/or
dysthymia. Since participants who received the treatment experienced significantly
more depression-free days over the 24-month-long study period than controls, the
ICER was low at $2,519$5,037 per QALY. Another long-term case management
program that was provided to primary care patients with major depression was found
likely to be cost-effective as well; in this study, the intervention group had also aver-
aged significantly more depression-free days than the control group after 24 months
(p < 0.01), though there was no significant difference in QALYs between the two
groups [45]. Bosmans and colleagues [46] evaluated a third depression management
program that consisted of screening, education, and treatment with paroxetine, but
determined that it was not likely to be cost-effective. The number of QALYs and
severity of depressive symptoms in the intervention and control groups were not dif-
ferent after 12 months of follow-up. Two studies examined relapse rates in popula-
tions of patients with remitted or partially remitted major depression; though both
treatments were successful at preventing relapse, one was found to be more cost-
effective [47, 48]. The administration of family psychoeducation sessions to one
member of each patients family, in addition to usual care, resulted in a lower risk of
relapse than usual care alone (HR = 0.17; 95 % CI = 0.04, 0.75; p = 0.002) [48]. Since
control group participants experienced more hospitalized days over the 9-month study
period, total costs were lower in the family psychoeducation group. A cost-effective-
ness analysis found that the intervention has a 90 % or greater chance of being cost-
effective if the decision maker is willing to pay $20 per relapse-free day.
9
9.5.2 Summary Table of Studies and Results (Table 9.3)
Table 9.3 Cost-benefit analyses of secondary prevention of late-life depression

Gensichen et al. 2013 RCT Primary care 562 12 months of case Mean costs, After 24 months, the intervention group had
(Jena, Germany) patients with management QALYs, DFDs experienced significantly more DFDs than
major depression including monitoring (depression- the control group (p < 0.01), though there was
of symptoms and free days) no significant difference in QALYs between
promoting medication the groups. While annual intervention cost
adherence was 276 per patient, there was no significant
difference in mean direct costs (4,495 vs.
3,506, p = 0.16), and the intervention group
had lower mean indirect costs (5,228 vs.
7,539, p = 0.06)
Bosmans et al. 2006 RCT Patients 55 125 Disease management QALYs, The direct costs of care for each group were
(Amsterdam, with major program that included MADRS not significantly different ($2,123 vs.
the Netherlands) depression screening, education, $2,259), but there was also no significant
and treatment with difference in QALYs or severity of depressive
paroxetine symptoms between the two groups at
follow-up. This intervention was therefore
not found to be cost-effective
Katon et al. 2005 RCT Patients 60 1,801 24 months-long QALYs, Patients receiving the intervention
(Seattle, WA) with MDD, IMPACT intervention DFDs, experienced 107 more depression-free days
dysthymia, or including education, outpatient over the 24-month period. The intervention
both problem-solving costs cost was $591/patient higher than usual care,
treatment, and and total outpatient costs were $295 higher.
medication adherence The incremental cost-effectiveness ratio was
therefore $2.76 per depression-free day and
estimated to be $2,519$5,037 per QALY
147
(continued)
148
Scott et al. 2003 RCT Psychiatric 158 20 weeks of weekly Relapse rate, Relapse rates were significantly lower in the
(London, UK) outpatients with cognitive therapy HAM-D, BDI cognitive therapy group than in the clinical
partially sessions and clinical management alone (control) group. After 17
remitted major management versus months of follow-up, relapse rates in the
depression clinical management intervention and control groups were 29 and
alone 47 %, respectively (HR = 0.51; 95 % CI
0.320.93). The cognitive therapy
intervention cost was 779/patient more than
conventional treatment, and the incremental
cost-effectiveness ratio was 4,328 per
relapse prevented. Though cognitive therapy
was found to be an effective intervention for
relapse prevention, the cost was high
Knapp et al. 2013 RCT Family 260 Eight sessions of a HADS-T, Average HADS scores in the intervention
(London, UK) caregivers of manual-based coping QALYs group were significantly lower than those in
people with strategy program the control group over the 8-month follow-up
dementia in the (psychological period (mean difference = 1.79; 95 %
START study intervention) in CI = 3.32, 0.33). The intervention group
addition to usual care also had borderline significantly greater
QALYs during this time, measured by the
EQ-5D (mean difference = 0.03; 95 %
CI = 0.01, 0.08). The costs of the manual-
based coping intervention were not
significantly higher, on average, than average
care (252; 95 % CI = 28, 565), and so the
intervention is likely to be cost-effective. The
average cost/QALY gained was 6,000, and
if decision makers are willing to pay up to
30,000 per QALY, there is a 99 % likelihood
of the START intervention being
cost-effective
9
Shimodera et al. 2012 RCT Adults 57 4 family Relapse-free Over the 9-month follow-up period, patients
(Kochi, Japan) diagnosed with psychoeducation days in the intervention group were less likely to
MDD, currently sessions that included relapse than those in the usual care group
in remission and one member of each (HR = 0.17; 95 % CI = 0.04, 0.75; p = 0.002).
undergoing patients family, in The intervention group also experienced a
maintenance addition to usual care significantly greater number of relapse-free
treatment days than the control group (p = 0.009). Since
control group participants had more
hospitalized days, total costs were higher in
this group than in the family psychoeducation
group. A cost-effectiveness analysis showed
that the intervention is likely to be cost-
effective regardless of what the decision
maker is willing to pay per additional
relapse-free day and has a 90 % or greater
chance of being cost-effective if they are
willing to pay $20/relapse-free day
Bosmans et al. 2012 RCT Primary care 175 46 problem-solving HADS, After 9 months of follow-up, the average
(Amsterdam, patients with therapy sessions QALYs change in HADS scores in the intervention
the Netherlands) mental health delivered by nurses (EQ-5D) group was not significantly different than that
problems (mean of the usual care group (mean
age = 53) difference = 0.2; 95 % CI = 3.7, 3.2). The
PST group had a greater number of QALYs
than the control group at the end of the study
period, though this difference was also not
significant (mean difference = 0.03; 95 %
CI = 0.02, 0.08). The average total costs of

the two groups were not significantly different,
though they were 2,062 lower in the PST
group (95 % CI = 4, 698, 359); cost-
effectiveness analysis therefore found that the
PST intervention was cost-effective when
149
compared with usual care

9.6 Summary
Late-life depression is associated with high burden in terms of economic costs,

healthcare burden of related comorbidity, and reduced quality of life. The high prev-
alence of depressive disorders in late life and growing proportion of the population
at older ages necessitate heightened attention to policies for screening and evalua-
tion of depression in this age group as well as formal assessment of the economic
considerations. Numerous brief self-report measures are available for the screening
of late-life depression, and agencies and organizations have developed guidelines
regarding selection, use, and interpretation of such screening tools. The use of such
screeners will have a particular benefit for identifying those most at risk of depres-
sion based on symptoms and, thus, amenable to indicated preventive interventions.
Finally, cost-benefit analyses have been undertaken in order to estimate the value of
screening and/or implementation of preventive interventions. Regarding screening,
questions remain regarding whether annual versus other intervals of screening are
most cost-effective. With respect to preventive interventions, the evidence to date
suggests that these are cost-effective in settings where those at the highest risk are
targeted. However, a major challenge for the future will be to answer the question of
how the cost-benefit calculus of preventive intervention in late-life depression is
affected by the development of extremely low-cost but effective preventive inter-
ventions that can be utilized on a large scale.
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48. Shimodera S, Furukawa TA, Mino Y, Shimazu K, Nishida A, Inoue S. Cost-effectiveness of
family psychoeducation to prevent relapse in major depression: results from a randomized
controlled trial. BMC Psychiatry. 2012;12:40.
Depression Among Blacks During Late
Life: Examining Within-Group Variations 10
Shanna Brewton-Tiayon, Daphne C. Watkins,
Niki Matusko, and James S. Jackson
Abstract
Depression is one of the most prevalent mental health disorders experienced
during late life. A life course perspective provides a useful frame to understand
depressive patterns, highlighting pivotal periods of mental health vulnerability
during important age-linked life stages. Research on Blacks during late life
commonly treats Blacks as a monolithic group, diminishing the returns that a
life course perspective can offer and perhaps masking within-group variations.
This chapter provides a review of the extant literature on depression prevalence
and depressive symptoms among African Americans and US- and foreign-born
Caribbean Blacks with a focus on the late-life period. We conduct an analysis of
lifetime major depressive episode, lifetime major depressive disorder, and depres-
sive symptoms for each group globally and disaggregated by gender. The results
show variations in prevalence rates and symptom patterns for each group as well
as interactions between ethnicity, nativity, and gender. Findings illustrate the
importance of targeted and tailored research, practice, and policy that can accom-
modate the variations within aging Black subgroups and their changing patterns
of mental health vulnerability and advantage over the adult life course.
Keyword
Aging Depression African American Caribbean Blacks Late life
S. Brewton-Tiayon, M.A. (*)

Department of Sociology, University of Maryland, 2112 Art-Sociology Building,
College Park, MD 20742, USA
e-mail: sbtiayon@umd.edu
D.C. Watkins, Ph.D.
School of Social Work, University of Michigan, Ann Arbor, MI, USA
N. Matusko, M.A. J.S. Jackson, Ph.D.
Institute for Social Research, University of Michigan, Ann Arbor, MI, USA

154 S. Brewton-Tiayon et al.
10.1 Introduction
Depression is one of the most common mental health disorders experienced by older
persons in the United States [1, 2]. Using a life course perspective to frame the analy-
sis of mental health disorders like depression is beneficial in that it highlights: the
cumulative effects of mental health risk factors across the life course; differential
exposure to social, physical, and environmental risk factors during different phases
of life; and cohort differences in mental health symptoms and prevalence [3, 4].
Research that centers on these factors is particularly important for mental health
practitioners who are focused on prevention. A life course perspective, focusing on
age-linked life stages, illuminates the need for targeted prevention strategies that
address age-related life transitions and associated mental health vulnerabilities.
A particular phase during the life course which is marked by increased physical
and social vulnerability is the late-life period. We demarcate late life into three peri-
ods: 5564 years, early late life; 6574 years, late life; and 75 years and older, late
late life.1 During late life, major role-based social and/or physical life transitions
may take place. For example, bereavement, changes in socioeconomic status (SES),
and physical illness all increase during late life, posing considerable changes in
feelings of control and autonomous functioning, which have been shown to influ-
ence mental health outcomes [57]. This chapter uses a life course perspective to
highlight depressive patterns during late life among older Blacks with a focus on
within-group differences.
The immigrant paradox states that while foreign-born populations initially have
better health than their US-born counterparts, this health advantage declines with
increased duration in the United States. However, the broader physical health litera-
ture suggests that this pattern does not hold for foreign-born Blacks, who maintain
their health advantage relative to US-born Blacks over time [8, 9]. The mental
health literature provides a body of research that argues that with respect to mental
health, ethnicity and nativity are more important than race. That is, within-group
differences in mental health patterns are most stark when differentiating along the
lines of ethnicity and nativity. Within racial groups, disorder prevalence rates vary
by ethnicity, and the foreign-born typically have lower rates than their US-born
counterparts [10, 11]. Combined physical and mental health literatures highlight the
importance of exploring within-group differences among ethnic minorities and sug-
gest a potential durability in the foreign-born Black immigrant health advantage
that may not exist for other immigrant groups.
Within-group differences in depression have been understudied among Blacks
generally and the late-life period specifically. Understanding mood disorders such
as major depression for Blacks is important because Blacks often go untreated and
depressive disorders can be more severe for Blacks as compared to Whites [11].
1
A challenge in ascertaining where the field stands in current late life research in mental health is
a lack of a clear partitioning of life course periods. For example, late late life can be defined as
those aged 75 years and older, 80 years and older, or 85 years and older [7, 19], which makes it
difficult to compare studies.
10 Depression Among Blacks During Late Life 155
Observed differences in depressive disorders and symptoms as a function of ethnic-

ity and nativity, the brevity of research documenting these differences among
Blacks, and the increased severity of depressive disorders among Blacks combine
to highlight the importance of racial and ethnic considerations in understanding
disorder pathways and a call to expand the literature on within-group differences to
be more inclusive of diversity among Blacks. This chapter aims to answer that call
by expanding what we know about late-life depression among Blacks, inclusive of
both African Americans and Caribbean Blacks. Using the adult life course perspec-
tive, the purpose of this chapter is to (1) provide a brief overview of the extant litera-
ture on depression correlates, symptoms, and prevalence for African Americans and
Caribbean Blacks; (2) provide an adult life course perspective of lifetime major
depressive episode (MDE), lifetime major depressive disorder (MDD), and depres-
sive symptoms for African Americans and US- and foreign-born Caribbean Blacks;
and (3) discuss the research, practice, and policy implications of depression among
subgroups of aging Blacks.
10.2 General Patterns of Late-Life Depression
A point of departure that may help us to understand late-life depression is to begin

with a brief overview of general research findings, without attention to racial or
ethnic differences. Also, looking at depressive patterns more generally allows us to
understand how Blacks conform to or deviate from these patterns. Reviews of exist-
ing studies on depression reveal several risk factors of depression for those in late
life: loss of a loved one, previous history of depression, female gender, comorbidity
(i.e., disability, physical or mental illness), low social support, and low SES [5, 6,
1214]. Despite the increased vulnerability to risk factors, studies have found that
the prevalence of depression during late life is low compared to earlier periods of
the adult life course, with women showing higher rates than men [15, 16].
Although there is no consensus on the definition of late life, researchers have
consistently disaggregated the late-life period into two or more age groups to under-
stand variation within and between these age-linked life stages. Findings are mixed
on the variation in depressive symptoms and depressive disorder prevalence for per-
sons during the different phases of later life. For example, some studies have reported
that persons in late late life demonstrated lower depressive symptom and disorder
prevalence rates [6, 17] while other studies report higher symptoms and prevalence
rates [1820] as compared to persons in the late-life period.2 Blazer [7, 21] suggests
that higher rates of depressive symptoms in the oldest of the old are associated with
factors related to the late late-life period such as a higher percentage of women,
greater disability, cognitive impairment, and lower socioeconomic status.
2
These results compare prevalence rates between the two oldest groups in each study, for example,
Blazer et al. [6], 60 to 74 years/75 years or older; Byers et al. [18], 75 to 84 years/85 years or older;
Murrell et al. [19], 65 to 74 years/75 years or older; Steffens et al. [20], 75 to 84 years/85 years or
older; and Steffens et al. [17], 80 to 89 years/90 years or older.
10.3 Aging and Depression Among US- and Foreign-Born

Blacks
10.3.1 Depression Rates Within and Between Black Samples
Data from the Epidemiological Catchment Area (ECA) studies show a pattern of
higher lifetime mood disorder prevalence during early adulthood for Black men and
women, with prevalence patterns that are fairly linear throughout the life course
showing incremental decreases in prevalence during each subsequent life phase
[22]. However, the ECA provides us with a monolithic interpretation of Black men-
tal health, treating all Blacks as one group and omitting within-group diversity.
More recent studies have attempted to address this gap, by exploring ethnic varia-
tions in mental health prevalence within Black samples. For example, analysis
using the Collaborative Psychiatric Epidemiology Surveys (CPES) provides us with
a more detailed understanding of variations in lifetime major depression prevalence
throughout the adult life course. Findings from the CPES show that Caribbean
Blacks in the early adult life course period (age 18 to 24 years) experienced the
highest lifetime prevalence rates for this group at 23.3 %. As for the late-life period
(55 years or older), lifetime prevalence rates were nonlinear with the highest preva-
lence for persons between 55 and 64 years (16.3 %), a significant drop for persons
6574 years (5.3 %), and a small increase for persons 75 years or older (7.1 %),
showing a small late late-life disadvantage. Patterns were slightly different for
African Americans with the highest prevalence rates found in persons between the
ages of 45 and 54 years old (15.2 %). Similar to Caribbean Blacks, African
Americans showed the highest prevalence rates during late life for persons 5564
years (10.2 %), a substantial drop for persons 6574 years (5.6 %), and an addi-
tional decrease for persons 75 years or older (2.1 %), mimicking a more linear pat-
tern as observed in the ECA studies and not showing a disadvantage for persons in
late late life as observed for Caribbean Blacks [23].
10.3.2 Correlates of Depression
US Blacks, particularly African Americans, experience many of the risk factors for
depression or depressive symptoms such as lower incomes and lower educational
attainment [24, 25]. Socioeconomic status is a correlate of depressive symptoms for
both older African Americans and Caribbean Blacks; however, socioeconomic sta-
tus works differently for each group. Increases in both income and education were
shown to be negatively correlated with depressive symptoms for older African
Americans, but only education was negatively correlated for older Caribbean Blacks
[26]. In addition to structural vulnerabilities, Blacks have been the subjects of sev-
eral studies that uncovered a link between discrimination and adverse mental and
physical health [2730], though there is limited knowledge on how discrimination
affects Blacks during the late-life period.
Findings regarding the relationship between marital status and depression are
mixed for Blacks. For older African Americans the relationship between marriage
and depressive symptoms emerges as statistically significant and protective in some

studies [31] and predominantly protective but not statistically significant in other
studies [26]. While marriage is protective for older Caribbean Blacks, it is only
significant when compared to separated (not divorced or widowed) Caribbean
Blacks. Separated older Caribbean Blacks experience higher depressive symptoms
as compared to married Caribbean Blacks, demonstrating a partial protective effect
of marriage for this group [26]. Further, Brown et al. [31] found that older African
American male heads of households reported fewer depressive symptoms as com-
pared to older African American female heads of households. Findings from this
study also showed that men who were previously married (i.e., divorced, separated,
or widowed) had higher depressive symptoms than previously married women, but
women who were never married had higher depressive symptoms as compared to
their male counterparts of the same status.
Some of the more common correlates of depression such as age and gender have
been inconsistent in mental health studies with Black samples. For example, in one
study, gender was not a significant correlate of depressive symptoms for older
African Americans or Caribbean Blacks, but age was a significant correlate of
depressive symptoms for older African Americans, showing an inverse relationship
[26]. Other studies have found that neither age nor gender was statistically signifi-
cant correlates of depressive symptoms for older African Americans [32]. Dividing
samples into low and high depressive symptom groups has provided stronger sup-
port for age and gender as correlates of depression among African Americans and
Caribbean Blacks; where those with lower depressive symptoms were more likely
to be older and male, and persons who had higher depressive symptoms were more
likely to be female [28].
Physical illness, disability, and cognitive impairment are all factors that dispro-
portionately impact persons in late life as compared to other periods during the
life course. Physical illness and disability (more specifically, stroke) were found
to increase depression prevalence among a community sample of foreign-born
Caribbean Blacks between the ages of 55 and 75 years old, living in the United
Kingdom [33].3 In a study of 215 adults aged 50 years and older who demon-
strated subthreshold depression, in comparison to older Whites, older Blacks had
higher levels of functional disability, comorbidity, and a higher mean CES-D
score [25].
10.3.3 Depressive Symptoms and Subthreshold Depression
Although individuals may not meet diagnostic requirements for major depressive
disorder or major depressive episode, they still may experience high levels of
depressive symptoms, sometimes referred to as subthreshold or nonmajor
3
This study used the Geriatric Depression Scale (GDS-10) and the Mini-Mental State Examination
(MMSE, 30 point). They lowered the cognitive impairment to 20 points to take into account
potential cross-cultural differences in MMSE distributions (p. 24), which may have produced
higher prevalence rates.
depression [21]. While not severe enough to meet clinical diagnosis, depressive
symptoms and subthreshold depression can have severe effects on the lives of indi-
viduals [13]. There is evidence that there are ethnic and nativity status variations in
subthreshold depression among Blacks. In a study of urban-dwelling older adults,
while Blacks overall demonstrated lower subthreshold depression as compared to
Whites, US-born Blacks and English-speaking Caribbean Blacks demonstrated sig-
nificantly higher levels of subthreshold depression as compared to Haitians [34].
These findings highlight the importance of understanding patterns in depressive
symptoms, even if the symptoms do not meet clinical threshold and suggest that a
focus on only racial differences in depressive symptoms may mask ethnic and nativ-
ity status disparities among Blacks.
Attempted suicide and suicide ideation are known symptoms of depression and
completed suicide is often an indicator of depression [35]. A review of racial and
ethnic patterns in suicide can provide some insight on variations in depressive
symptoms. The suicide completion rate in the United States across race, age, and
sex was 12.43 out of every 100,000 individuals in 2010. This rate was higher during
all periods of late life: 5564 years old (17.50/100,000), 6574 years old
(13.70/100,000), and 75 years old or older (16.28/100,000),4 marking the vulnera-
bility of the late-life period for suicide. White men had the highest suicide comple-
tion rate during the late late-life (75 years or older) period with a rate of
40.07/100,000, compared to Black men (9.57/100,000) and all other male groups.
Throughout the late-life period (55 years and older), Black women maintained the
lowest rates of all Black/White, male/female groups [36].
Within-group differences of suicide ideation and attempted suicide tell a slightly
different story. Focusing on Blacks in the National Survey of American Life
(NSAL), one of three surveys within the CPES, suicide ideation and attempted sui-
cide were highest for Caribbean Black men (13.6 and 7.5 %, respectively) and
African American women (12.8 and 5.0 %, respectively), with Caribbean Black
women and African American men showing the lowest prevalence rates. Compared
to earlier periods in the life course, the study finds that the oldest birth year cohorts,
those born in 1939 or before, showed the lowest prevalence rates of suicide ideation
(3.5 %) and attempts (0.9 %) among all cohorts [37]. On a related topic, personal
assessments of happiness also provide another perspective of variations in depres-
sive symptoms, with happiness serving as a measure of an individuals subjective
state of psychological well-being. Of persons 55 years and older, African Americans
showed higher levels of happiness relative to Caribbean Blacks. Duration in the
United States was a predictor of subjective assessments of happiness for foreign
born Caribbean Blacks. Those who resided in the United States 35 years or less had
higher levels of happiness than US-born Caribbean Blacks [26].
4
Figures reported in crude non age-adjusted rates taken from the Center for Disease Control and
Prevention Web-based Injury Statistics Query and Reporting System
10.3.4 Rationale for This Study
Previous studies have suggested that among older adults (defined as aged 50 years
and older), African Americans have higher rates of lifetime major depressive episode
when compared to Caribbean Blacks (9.0 % vs 7.5 %, respectively). Further analysis
showed that, while not statistically significant, older US-born Caribbean Blacks had
considerably higher prevalence rates for any depressive disorder, at 16.4 %, as com-
pared to foreign-born Caribbean Blacks at 5.9 % [38]. A similar analysis using the
NSAL reported a linear pattern of decreased lifetime major depressive disorder prev-
alence throughout the adult life course for Caribbean Blacks, with those 60 years or
older showing the lowest prevalence rates. African Americans demonstrated a simi-
lar pattern with the difference of a slight uptick in prevalence during the period of
4559 years, but similar to Caribbean Blacks, those 60 years and older showed the
lowest prevalence rates [11]. In the context of these findings, this chapter builds on
the work of previous scholars by expounding on depression research with aging
Black samples. Specifically, our aim is to first synthesize recent findings on sub-
groups of aging Blacks (African Americans and Caribbean Blacks) using an adult
life course perspective. Then, we will report the findings from the NSAL on lifetime
major depressive episode (MDE), lifetime major depressive disorder (MDD), and
depressive symptoms for aging African Americans and US- and foreign-born
Caribbean Blacks. Though this study will examine the rates of MDE, MDD, and
depressive symptoms over the adult life course for Blacks, we pay particular atten-
tion to the late life period because previous studies of this period with Black samples
have been inconsistent.
10.4 Approach to the Study
10.4.1 Sample
The National Survey of American Life (NSAL) is a comprehensive study of the

mental health of Black Americans [39]. The study, conducted between February
2001 and June 2003, as part of the NIMH Collaborative Psychiatric Epidemiology
Surveys (CPES) initiative [40]. The NSAL adult sample is an integrated national
household probability sample of 3,570 African Americans, 1,621 Blacks of
Caribbean descent (Caribbean Blacks), and 891 non-Hispanic Whites living in areas
where at least 10 % of the population is Black, all age 18 and over [39]. In both the
African American and Caribbean Black samples, it was necessary for respondents
to self-identify as Black. Those self-identifying as Black were included in the
Caribbean Black sample if they answered affirmatively when asked if they were of
West Indian or Caribbean descent or if they said they were from a country included
on a list of Caribbean area countries provided by the interviewers.
Most interviews were conducted face-to-face using a computer-assisted instru-
ment and lasted an average of 2 h and 20 min. The final overall response rate was
72.3 % but 70.7 % for the African American sample, 77.7 % for Caribbean Blacks,
and 67.7 % for the non-Hispanic White sample. The NSAL is weighted to correct
for disproportionate sampling and nonresponse and to provide representation across
various demographic characteristics in the coterminous states. The focus of this
paper includes all NSAL African American and US- and foreign-born Caribbean
Black respondents.
10.4.2 Measures
10.4.2.1 Sociodemographic Characteristics

Sociodemographic characteristics included ethnicity (African American or
Caribbean Black) and nativity (US-born and foreign-born Caribbean Black). Age
represented the age at the time of the interview and was coded into five categories:
1834 years old (early adult), 3554 years old (mid-adult), 5564 years old (early
late life), 6574 years old (late life), and 75 years or older (late late life). Male and
female sexes were coded as dummy variables in the analysis.
10.4.2.1 Major Depressive Disorder and Major Depressive Episode

We used the World Mental Health CIDI, a fully structured diagnostic interview, to
evaluate major depressive disorder (MDD) and major depressive episode (MDE).
The psychiatric disorders assessed in the NSAL, which included MDD, are slightly
modified versions of those developed for the World Mental Health project initiated
in 2000 [41] and used in the NCS-R [42]. The DSM-IV criterion for major depres-
sive disorder requires the presence of one or more major depressive episodes
(MDE)the presence of depressive symptoms, including either depressed mood
and/or loss of interest or pleasure, lasting 2 weeks or longer, most of the day, nearly
every day, as well as clinically significant distress or impairmentwithout a history
of manic, mixed, or hypomanic episodes. The depressive episode must not be due
to the direct physiological effects of a drug of abuse, a medication, or toxic exposure
nor better accounted for by schizophrenia or another psychotic disorder. The algo-
rithm for MDD is the same as that for major depressive episode (MDE): criteria C,
the presence or absence of a manic episode, is not considered. The Structured
Clinical Interview for DSM-IV (SCID; [43]), a diagnostic interview that requires
administration by a clinician, was used in the reappraisal study to generate the diag-
nosis of MDE. A comparison of the CIDI and the SCID for MDE for respondents in
the clinical reappraisal sample indicates fair concordance for African Americans
( = 0.43; 95 % confidence interval [CI], 0.26 to 0.59) but much lower concordance
for Whites ( =0.27; 95 % CI, 0.13 to 0.67) and Caribbean Blacks ( =0.10; 95 %
CI, 0.19 to 0.39) [11].
10.4.2.2 Depressive Symptoms

Depressive symptoms were assessed using the 12-item version of the Center for
Epidemiological Studies-Depression Scale (CES-D) [44]. This abbreviated
CES-D has been found to have acceptable reliability and a similar factor
structure compared to the original version. Item responses are coded 1 (hardly
ever) to 3 (most of the time). These 12 items measure the extent to which respon-
dents had trouble keeping their mind on tasks, enjoyed life, had crying spells, could
not get going, and felt depressed, hopeful, restless, happy, as good as other people,
that everything was an effort, that people were unfriendly, and that people dislike
them in the past 30 days. Positive valence items were reverse coded and summed
resulting in a continuous measure; a high score indicates a greater number of depres-
sive symptoms (M = 6.51, SE = 0.23) (Cronbachs alpha = 0.75).
10.4.3 Analytical Strategy
Specialized statistical techniques were used to account for the multistage sample
design of the NSAL. Standard errors were corrected for clustering and stratification.
All analyses were conducted using STATA 11 which uses the Taylor expansion
approximation technique for calculating the complex design-based estimates of
variance [45]. Cross tabulations and mean scores are presented to show unadjusted
age cohort differences on prevalence rates of lifetime MDD, MDE, and CES-D
scores. The percentages and mean scores represent weighted proportions and means
based on the samples weight measure and the standard errors have been corrected
for the complex design. The significance lever was set to p < 0.05.
10.4.4 Results
Sociodemographic characteristics and racial and ethnic profiles of the NSAL

sample are not presented in this chapter because they have been published else-
where [11, 23, 40, 46]. Moreover, for the purposes of this chapter, our results under-
score the age period patterns of MDD, MDE, and depressive symptoms by ethnicity,
nativity, and gender.
10.4.4.1 Patterns of MDD, MDE, and Depressives Symptoms

by Ethnicity and Nativity
US-born Caribbean Blacks demonstrated the most consistent pattern of disadvantage
across measures of MDD, MDE, and depressive symptoms throughout the age peri-
ods examined (Table 10.1). There were some age periods where US-born Caribbean
Blacks prevalence rates or mean CES-D scores fell below African Americans and
foreign-born Caribbean Blacks. Specifically, during the late-life period (6574 years),
US-born Caribbean Blacks reported lower MDE prevalence rates than did the other
Black groups, with an MDE prevalence rate of 2.5 % compared to 5.8 % for African
Americans and 6.0 % for foreign-born Caribbean Blacks. This pattern of advantage
remained during this same age period for MDD. Similarly, depressive symptoms
for US-born Caribbean Blacks began to decline during late life (6574 years),
marking late-life as a pivotal period for Blacks who otherwise show mental health
disadvantage during earlier age periods.
162
Table 10.1 Unadjusted prevalence rates of lifetime DSM-IV/WMH-CIDI major depressive episode, major depressive disorder, and depressive symptoms in
the NSAL sample by race and ethnicity
African American U.S. Born Caribbean Black Foreign Born Caribbean Black
Lifetime Lifetime Lifetime Lifetime
Lifetime Major Lifetime Major Major Major Major Major
Depressive Depressive Depressive Depressive Depressive Depressive Depressive Depressive Depressive
Episode Disorder Symptoms Episode Disorder Symptoms Episode Disorder Symptoms
% SE % SE Mean SE % SE % SE Mean SE % SE % SE Mean SE
n = 3434 n = 3433 n = 3578 n = 432 n = 432 n = 432 n = 1141 n = 1141 n = 1141
Age
1834 12.7c,d 1.1 10.1c,d 0.8 7.4b,c,d 0.2 21.7 6.3 20.3 6.5 7.3d 0.8 15.3 4.7 13.2 4.7 7.0a 0.7
3554 14.1e,f,g 1.1 11.9 f 1.1 6.7e,f 0.3 18.6 5.5 18.1 5.5 8.3g 2 8.7 2 8 1.9 5.2 0.4
5564 9i 1.6 8.4i 1.5 5.6 0.4 42 17.8 42 17.8 7.8 2.4 3.4 1.7 3.2 1.7 5.6 0.7
6574 5.8 1.5 5.8j 1.5 5.1 0.3 2.5 2.6 2.5 2.6 4.9 1.4 6 4.6 6 4.6 5.2 1.5
75 2.2 0.9 1.6 0.7 4.7 0.5 7.4 8 7.4 8.1 2.2 1.7 6 3.6 6 3.6 6 0.8
Design- 7.1* 5.6* 1.7 1.7 1.9 1.3
based F
*p < 0.05
The following contrasts are significant at the p < 0.05 level: a1834 vs. 3554; b1834 vs. 5564; c1834 vs. 6574; d1834 vs. 75+; e3554 vs. 5564; f3554 vs.
6574; g3554 vs. 75+; h5564 vs. 6574; i5564 vs. 75+; j 6574 vs. 75+
S. Brewton-Tiayon et al.
There was no late late-life (75 years or older) advantage for US-born Caribbean
Blacks for MDE and MDD. Instead, there was a small increase in prevalence rates for
this group during late late life. However, there was an advantage for depressive symp-
toms which declined from the late life to late late-life periods. US-born Caribbean
Blacks reported the lowest mean CES-D scores during the late late-life period among
all groups observed in our analysis. Also, looking at patterns across groups revealed
that the MDE and MDD patterns mimic each other depicting a similar graphical
representation across the age periods examined (Figs. 10.1 and 10.2).
Relative to foreign-born Caribbean Blacks, African Americans maintained
higher MDE prevalence rates during the mid-adult (3554 years) to early late-life
(5564 years) periods, with prevalence rates of 14.1 % compared to 8.7 % for
foreign-born Caribbean Blacks during the mid-adult period and prevalence rates of
9.0 % as compared to 3.4 % for the early late-life period. An African American
disadvantage was present during these same periods for MDD as well. Interestingly,
during the early late-life (5564 years) period, depressive symptoms for African
Americans and foreign-born Caribbean Blacks converge with a mean CES-D score
of 5.6; however, during the late late-life period, foreign-born Caribbean Blacks
50
40
Percentage
30
20
10
0
18-34 35-54 55-64 65-74 75
Age
African Americans U.S. born Caribbean Blacks
Foreign born Caribbean Blacks
Fig. 10.1 Lifetime major depressive episode prevalence rates
45
40
35
Percentage
30
25
20
15
10
5
0
18-34 35-54 55-64 65-74 75
Age
Fig. 10.2 Lifetime major depressive disorder prevalence rates

demonstrate the highest mean CES-D score among all Black groups at 6.0. Overall
African Americans demonstrated a linear pattern of change across the age periods,
in that depressive symptoms decreased from the mid-adult (3554 years) period
onward (Fig. 10.3).
10.4.4.2 Patterns of Depressive Symptoms by Ethnicity,

Nativity, and Gender
Aggregate measures of depressive symptoms, shown in Table 10.1 and graphically
represented in Fig. 10.3, included both males and females of each ethnic group.
Results showed higher US-born Caribbean Black mean CES-D scores for the early
adult (3554 years) and early late-life (5564 years) periods, relative to all groups,
followed by very similar depressive symptom patterns during the late-life period
(6574 years) for all groups and a foreign-born Caribbean Black disadvantage and
US-born Caribbean Black advantage during late late life (75 years and older).
US-born Caribbean Black mean CES-D scores were higher than their foreign-born
counterparts throughout the age periods analyzed with the exception of the late life
(6574 years) and late late life (75 years and older).
An analysis of depressive symptoms by gender underscores US-born Caribbean
Black men as the group experiencing more disadvantage with regard to the depres-
sive symptoms when compared across all age periods studied (Fig. 10.4).5
The higher US-born Caribbean Black male CES-D scores drove up the mean CES-D
scores for the group as a whole, essentially masking the lower female US-born
10
Mean CES-D Score
0
18-34 35-54 55-64 65-74 75
Age
African Americans U.S. born Caribbean Blacks
Foreign born Caribbean Blacks
Fig. 10.3 Mean CES-D scores
5
There were a few cells in our depressive symptom by ethnicity and gender analysis that had fewer
than 25 observations; this occurred exclusively for observations during the late life period for the
US-born Caribbean Black sample. Specifically for the early late-life period (5564 years): US-born
Caribbean Black male (n = 10) and US-born Caribbean Black female (n = 11). For the late life
period (6574 years): US-born Caribbean Black male (n = 10) and US-born Caribbean Black
female (n = 8). For the late late life period (75 years or older): US-born Caribbean Black male
(n = 1) and US-born Caribbean Black female (n = 5).
11
Mean CES-D Score 9

7
5
3
1
1
18-34 35-54 55-64 65-74 75+
Age
African Americans Males US Born Caribbean Males
Foreign Born Caribbean Males
Fig. 10.4 Male mean CES-D scores by ethnicity
Caribbean Black mean CES-D scores for all periods of the life course, relative to
US-born Caribbean Black males (Fig. 10.2). US-born Caribbean Black men showed
considerably higher mean CES-D scores than foreign-born Caribbean Blacks and
African Americans. For example, focusing on the late-life period (6574 years),
US-born Caribbean Blacks had a mean CES-D score of 9.7, compared to 5.6 for
African Americans and 5.2 for foreign-born Caribbean Blacks.
African American males had a lower mean CES-D score during the early late life
(5.3) as compared to foreign-born Caribbean Blacks (5.9), losing this advantage dur-
ing the late life (6574 years) with a mean CES-D score of 5.6 compared to 5.2 for
foreign-born Caribbean Black men and regaining this advantage during the late late
life (75 years or older) with a mean CES-D score of 4.9 compared to 6.2 for foreign-
born Caribbean Black men. US-born Caribbean Black females reported the highest
mean CES-D score across all female groups during early late life (5564 years) with
a score of 6.9 as compared to 5.7 for African American females and 5.2 for foreign-
born Caribbean Black females (Fig. 10.5). However, US-born Caribbean Black
females reported the lowest depressive symptoms among all groups (both male and
female) for the late-life (2.1) and late late-life (2.3) periods. The depressive symptom
patterns for African American females during late life remained consistently between
the mean CES-D scores for the US-born and foreign-born Caribbean Blacks.
10.5 Discussion and Implications
The purpose of this chapter was threefold. First, our aim was to provide a brief
overview of the extant literature on depression correlates, symptoms, and preva-
lence for African American and Caribbean Blacks. Next, we provided an adult life
course perspective to an examination of lifetime MDE, lifetime MDD, and depressive
symptoms for African Americans and US- and foreign-born Caribbean Blacks in an
11
Mean CES-D Score 9
1
18-34 35-54 55-64 65-74 75+
Age
African Americans Females US Born Caribbean Females
Foreign Born Caribbean Females
Fig. 10.5 Female mean CES-D scores by ethnicity
effort to underscore the potential disparities among those in late life. Here, we will
meet our final aim by discussing our findings in the context of their future research,
practice, and policy implications. Overall, our findings suggest that while aging
groups may share common experiences directly linked to aging, there are various
social factors that differentiate the experiences of persons during late life. In the
case of this chapter, we argue that ethnicity and nativity are important, yet often-
times underreported factors that contribute to the mental health transitions for aging
populations. Therefore, in order to gain a more nuanced understanding of patterns
during the late-life period, it is important to consider how intersecting determinants
such as ethnicity and nativity should be considered.
We found that African Americans, US-born Caribbean Blacks, and foreign-born
Caribbean Blacks did not show the same patterns of MDE and MDD prevalence or
depressive symptoms in the analysis. Specifically, in this chapter, US-born Caribbean
Blacks demonstrated the greatest disadvantages among all groups, suggesting chal-
lenges unique to this group that do not impact African Americans and foreign-born
Blacks in the same way. Research in this area should also take heed to the potential
vulnerabilities of US-born versus foreign-born Caribbean Blacks and how they dif-
fer from African Americans. Particular attention should be given to how researchers
reach these groups through recruitment efforts, as well as the cultural sensitivity of
the instruments used to assess their mental health.
Effective strategies to understand the etiology, manifestation, and treatment of
depression among US-born Caribbean Blacks must first attend to the unique psycho-
social stressors faced by this group and assess potential vulnerabilities in their coping
mechanisms which place them at such extreme disadvantage [11]. It is clear that an
analysis of mental health patterns that treat Blacks as a monolithic group is incom-
plete and insufficient in designing preventative programs. Such programmatic efforts
would benefit from federal support in the form of monetary and staff allocations
designed to address the state- and community-level mental health challenges associ-
ated with ethnic and nativity relations. Large, complex sample surveys such as the
NSAL paired with US Census data can help pinpoint priority areas.
Our analysis also suggests that there are pivotal periods of change over the adult
life course that mark patterns of advantage or disadvantage for each ethnic and
nativity group. For example, despite their disadvantage during all other age-linked
life stages, US-born Caribbean Blacks demonstrated the lowest depression preva-
lence rates during the late-life (6574 years) period. In contrast, foreign-born
Caribbean Blacks experienced an increase in depression prevalence rates during
this same period. These findings indicate the unique contribution that acculturation
makes to aging Blacks. Our findings are specific to age-linked life stages (or cohorts)
and, therefore, cannot be interpreted as a life course analysis. However, our findings
do influence the life course perspective and have implications for future research on
aging Blacks. For instance, an important next step will be identifying when (over
the adult life course) does the vulnerability to depression change for specific
groups. While each individual is different, identifying ethnic- and nativity-specific
patterns will prove to be useful in designing preventative strategies. Perhaps one
approach would be for these strategies to address the periods of potential vulner-
ability by finding a way to mimic the periods of healthy psychological well-being.
Resources designated to unpack the complexities of aging racial and ethnic minor-
ity groups may influence the life expectancy of these groups.
An important aspect of our findings is the interaction we found between ethnicity,
nativity, and gender. In terms of mental health outcomes, US-born Caribbean Black
men were largely more disadvantaged than their female counterparts and demon-
strated higher mean CES-D scores throughout each age-linked life stage (Figs. 10.4
and 10.5). Thus, it is likely that programs and strategies that target US-born Caribbean
Blacks more broadly will miss the additional complexities that are the result of gender
differences. Because US-born Caribbean Black males vulnerability to depressive
symptoms differs from US-born Caribbean Black females, future studies should con-
sider a more in-depth analysis that will uncover the differences in gender norms and
gender ideologies for US-born Caribbean Blacks. These research findings could then
be translated into programs that target specific Caribbean Black communities in the
United States and evaluated for its process and outcome success.
Our findings also revealed that, regarding their depressive symptom prevalence,
US-born Caribbean Black men were more comparable to other Black men during the
early adult life period (1834 years). This may suggest that something important
happens during that period (or closer to the end of that period) that changes their
mental health trajectories. These findings highlight the need for more early interven-
tions that educate Black men and women about the implications of ethnic and nativ-
ity differences during certain periods of life and empower them to become more
vigilant and proactive with their mental health and well-being, especially during
early adulthood. Perhaps national campaign efforts that target young adults could try
to implement more ethnic-, nativity-, and gender-specific strategies to improve the
mental health outcomes for these subgroups.
10.6 Conclusion
Previous mental health literature suggests that, with respect to mental health,
ethnicity and nativity may be more important factors to consider than race. In other
words, within-group differences in mental health patterns are most stark when dif-
ferentiating along the lines of ethnicity and nativity. Within racial groups, mood
disorder prevalence rates vary by ethnicity; the foreign-born typically have lower
rates compared to their US-born counterparts. Although there is an expanding body
of research about within- and between-group differences in mood disorder risks,
symptoms, and prevalence rates among Hispanic and Asian groups, the comparable
analyses of within-group differences among Blacks are evolving at a slower pace.
Lack of both breadth and depth in understanding the intersecting domains among
subgroups of Blacks over the adult life course can provide a less than comprehen-
sive understanding of depressive disorders for these subgroups. Findings from the
within-group analysis of group differences for MDE, MDD, and depressive symp-
toms among Blacks in this chapter highlight three areas of importance for mental
health professionals and practitioners concerned with the prevention of depression
during the late life: (1) the heterogeneity of MDE, MDD, and depressive symptom
patterns for Black subgroups; (2) the pivotal shift of advantage or disadvantage dur-
ing certain age-linked life stages for Black subgroups; and (3) the important interac-
tions among gender, ethnicity, and nativity in determining mental health outcomes.
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Global Priorities and Possibilities
11
Steven M. Albert, Offer E. Edelstein, Stewart J. Anderson,
Mary Amanda Dew, and Charles F. Reynolds III
Abstract
The high prevalence of poor mental health at later ages is a central challenge for all
countries; however, it is a greater challenge for low- and middle-income countries
(LMICs). Recognizing this challenge, WHO and other organizations have launched
several global initiatives to address disparities in access to mental health clinical
specialists in LMICs. Greater educational efforts are needed to ensure proper identi-
fication of late-life depression and reduce stigma and discrimination associated with
mental illness. Efforts should be invested in developing more accurate and brief diag-
nostic tools. The shortage of mental health specialists requires task sharing using
non-clinicians to triage symptoms and therapies and support adherence to pharmaco-
therapy. Diagnosis and treatment of depressive disorders in primary care settings in
LMICs is feasible, cost-effective, and likely to reduce spillover morbidity (i.e.,
effect of mental illness on family members). Research on the experience of mental
illness and treatment among LMIC populations is required to guide these efforts.
S.M. Albert (*) O.E. Edelstein S.J. Anderson M.A. Dew

Health, University of Pittsburgh, Parran Hall 208, Pittsburgh, PA 15261, USA
e-mail: smalbert@pitt.edu
C.F. Reynolds III

172 S.M. Albert et al.
Keywords
Low- and middle-income counties (LMICs) Late-life depression Prevention
Treatment Cost-effectiveness
11.1 Introduction
Global mental health has moved beyond old debates that pit claims of the universality
of psychiatric diagnoses against the particularity of culture-bound syndromes. We
know now that mental illness is a feature of all societies and shares common risk fac-
tors, even if local conditions affect the experience of mental disorders. Impaired men-
tal health is reliably associated with similar conditions in both high- and low- and
middle-income countries (LMICs). For example, poor mental health is universally
associated with social disadvantage, disability, and stigma [1]. By the same token,
patients with mental health conditions, wherever they live, also respond to a common
set of effective pharmacologic and psychosocial treatments. Similarly, prevention
efforts using appropriate clinical resources have been shown to reduce the incidence
of psychiatric syndromes in settings as different as the United States and India.
This chapter extends discussion of mental health, and especially late-life depres-
sive disorders, to the global theater. We assay current approaches to global mental
health, first defining the global perspective and the global prevalence of mental, neu-
rological, and substance abuse and related disorders (grouped in WHO nomenclature
as MNS). We then summarize the current state of thinking on global issues relating
to recognition of depressive disorders, treatment in diverse settings, prevention, and
delivery of mental health services. We conclude with thoughts on the global impact of
reducing depressive orders and potentially other mental health problems in late life.
11.2 Taking a Global Perspective
The World Bank classifies state economies according to gross national income per
capita (http://data.worldbank.org/about/country-classifications) [2]. Income infor-
mation compiled by the World Bank is available for member countries (188) and
other economies with populations of more than 30,000 (another 26 entities). In this
classification, citizens of low-income countries earn $1,025 or less annually.
Middle-income countries are divided into lower middle income, $1,026$4,035,
and upper middle income, $4,036$12,475. High-income countries are character-
ized by annual per capita incomes of $12,476 or more. Income is strongly associ-
ated with health outcomes. In high-income countries, life expectancy at birth in
2011 was as high as 83 in Japan (and age 78 overall) but only 4849 in some low-
income countries (Lesotho, Swaziland, Afghanistan, Zambia). The age structure of
populations follows this pattern. Currently, nearly a quarter of Japans population is
over age 65, but in low-income sub-Saharan African countries, only 4 % of the
population has reached this age milestone.
The UN classifies countries as more developed or less developed (with a sub-
set of 50 countries considered least developed), roughly corresponding to the World
11 Global Priorities and Possibilities 173
Table 11.1 Distribution of More developed countries Less developed countries

population at older ages,
Age Population % Total Population % Total
more and less developed
countries, 2013 Total 1,246,044,208 5,849,173,772
60+ 286,299,646 23 559,743,766 9.6
65+ 209,944,236 16.8 368,844,926 6.3
70+ 149,798,520 12 232,244,928 4
75+ 98,386,763 7.9 131,452,967 2.2
80+ 57,537,741 4.6 61,306,114 1
85+ 27,695,698 2.2 21,681,356 0.4
90+ 9,709,455 0.8 5,231,354 0.1
95+ 2,245,103 0.2 823,236 <0.1
100+ 378,087 <0.1 84,420 <0.1
Source: US Census, International Data Base. Midyear estimates.
http://www.census.gov/population/international/data/idb/infor-
mationGateway.php
Bank categories. In 2013, the population of the more developed countries was 1.25
billion, and the population of less developed countries 5.85 billion. Table 11.1 shows
great differences in age structure across the income categories. In the more devel-
oped countries, 23 % were over age 60 in 2013. In the less developed countries, only
9.6 % had reached this age, a 2.5-fold difference. For age 80 or older, differences are
even more pronounced: 7.8 % of the population in more developed countries and
1.5 % in less developed countries, a fivefold difference. The difference in the oppor-
tunity to reach older ages, however, should not be interpreted as absence of the very
old in LMICs. As shown in Table 11.1, the absolute number of the very old, indicated
by people aged 80+, is not very different across the world: 97.6 million in more devel-
oped countries, 89.1 million in less developed countries. Because of the growing num-
ber of older adults, LMICs face new epidemics of the diseases of late life.
The high prevalence of chronic noncommunicable diseases and poor mental
health at later ages is a central challenge for all countries, whatever their income
status. In fact, it is a greater challenge for LMICs. World Bank data show that health
expenditures per capita vary considerably across country income categories, with
annual per capita expenditures under $100 in some low-income countries but over
$8,000 in the United States (in 2001 dollars), for example. Low-income countries
have less than 20 physicians per 100,000 residents, while high-income countries
may have as many as 500 or more (as in some countries of the European Union).
The World Development Indicators of the World Bank provides detail on a variety
of health access indices by country useful for tracking global disparities (http://
databank.worldbank.org/data/views/variableselection/selectvariables.aspx?source=
world-development-indicators) [3].
Disparities in access to mental health clinical specialists are even greater. Polling
of neurologists by the World Federation of Neurology suggests differences in access
between countries ranging from 6,240 people per neurologist in Europe to over
4 million per neurologist in Africa [4]. A survey of 192 countries, reported in the
World Health Organization Mental Health Atlas [5], shows that the number of
psychiatrists per 100,000 people ranges from 9.8 in Europe to <0.04 in Africa.
Disparities in resources, personnel, and access to psychiatric services continue and
show little signs of change, as shown in the most recent edition of the WHO Mental
Health Atlas [6], which provides country-level descriptions of mental health policy
governance, financing, and information systems, as well as estimates of mental
health-care services delivery, access to clinicians and medications, and workforce
training. Figure 11.1 shows the extreme differences in availability of mental health
resources globally.
LMICs thus face a perfect storm of challenges for addressing the mental health
needs of older populations. Elements of this storm include rapid population aging
(carrying with it greater prevalence of chronic conditions recognized as risk factors
for depression), concentration of populations in urban centers (weakening tradi-
tional social supports), absent or still emerging social insurance systems (making it
difficult to fund mental health services), and underdeveloped mental health services
infrastructure (limiting access to effective treatments).
Recognizing these challenges, world bodies along with nongovernmental organi-
zations have increased efforts to address global mental health. Some of the more
prominent efforts include the WHO Mental Health Gap Action Programme
(mhGAP) [7]. The program seeks to scale up services for mental, neurological, and
Fig. 11.1 Rate of mental health professionals per 100,000 population by WHO Member State,
WHO Mental Health Atlas 2011. Reprinted with permission, WHO
substance use disorders in low- and middle-income countries (http://www.who.int/

mental_health/mhgap/en/).
At its fourth global forum, mhGAP Forum vetted its 2012 Action Plan (http://
www.who.int/mental_health/mhgap/forum_2012/en/index.html). The plan addresses
mental health over the life span but includes many features relevant to the second 50
years of life: comorbidity of physical and mental disorders, discrimination, social
determinants of health, spirituality, recovery, quality of health and social services,
culture, suicide, vulnerable populations, scaling up and integrating mental health
care into primary health care, caregiver and family support, role of NGOs, gender
differences in mental health, and the role of e-mental health tools in implementation.
In May 2013, the WHO World Health Assembly presented its draft comprehensive
mental health action plan for 20132020. An allied effort is the WHO/World
Federation for Mental Health World Mental Health Day (celebrated on October 10
each year). The 2013 theme was Mental health and older adults (http://www.who.
int/mental_health/en/).
Another initiative is the National Institute of Mental Health (NIMH)-sponsored
Collaborative Hubs for International Research on Mental Health (CHIRMH). This
program established regional hubs in different parts of the world to increase research
in mental health interventions in LMICs. CHIRMH explicitly seeks to reduce the
mental health treatment gap, defined as the proportion of persons who need but do
not receive care. As NIMH notes, the treatment gap for mental disorders across the
world is large and leads to chronic disability and increased mortality for those
affected. The program requires that each regional hub must have an existing on-
site administrative structure in its respective region along with scientific and men-
toring capacity. To date, NIMH has funded five such hubs: AFFIRM (AFrica Focus
on Intervention Research for Mental health) in sub-Saharan Africa, RedeAmericas
in South America, SHARE (South Asian Hub for Advocacy, Research and Education
on mental health) in South Asia, LATIN-MH (Latin America Treatment and
Innovation Network in Mental Health), and PaM-D (Partnership for Mental Health
Development in Sub-Saharan Africa).
A related effort is the Global Alliance for Chronic Diseases (GACD) (http://
www.gacd.org/), launched in 2009 [8]. The Alliance consists of national health
research institutions (in the United States, the National Heart, Lung, and Blood
Institute of NIH) and seeks to address prevention and treatment of chronic noncom-
municable diseases, including mental illness. GACD focuses on LMICs and the
low-income populations of more developed countries. The Alliance is broad and
represents about 80 % of public health research funding worldwide. Member orga-
nizations include National Health and Medical Research Council (Australia),
Institutes of Health Research (Canada), Ministry of Health and Academy of Medical
Sciences (China), Medical Research Council (UK), NIH (US), Medical Research
Council (India), Medical Research Council (South Africa), and the European
Commission. Partners include the Pan American Health Organization, World Heart
Federation, and National Institute for Medical Research (Tanzania).
GACD was part of the initial Grand Challenges Global Partnership (announced
in 2007), which established priorities for reducing the burden of cardiovascular
diseases, type 2 diabetes, chronic respiratory diseases, and certain cancers, which
together account for about 60 % of all deaths worldwide. Mental health is part of the
GACD agenda and will undoubtedly become more prominent.
Consistent with this growing effort in concern for global mental health is a series
of new journals and opportunities for dissemination of research. For example,
Lancet Global Health, launched in 2013, will focus exclusively on health in low-
and middle-income countries and includes mental health as a key topical domain.
PLoS Medicine has also established a series on Global Mental Health Practice.
Public education efforts for global mental health have also taken hold. An impor-
tant effort is the Global Mental Health-Map (GMH-Map) [9], https://sites.google.
com/site/gmhmap. GMH-Map is an effort of the Office of International Affairs,
American Psychological Association. The website includes an extensive compila-
tion of resources to help people get a clearer sense of the GMH domain and to
meaningfully connect and contribute to it.
11.3 Global Prevalence of Mental, Neurological,

and Substance Abuse and Related Disorders (MNS)
The prevalence and distribution of mental health disorders worldwide have become
clearer through a series of cross-national population surveys that rely on screening
and standardized clinical interviews, including the WHO Mental Health Surveys
[10]. Using major depressive episodes (MDE) as an example, early results sug-
gested substantial variability in 12-month age-adjusted prevalence, ranging from
<1 % in Taiwan to 6 % in New Zealand [11]. Using the World Mental Health
Composite International Diagnostic Interview (CIDI)-DSM-IV, age-adjusted
12-month MDE prevalence was higher in the United States and Europe (3.69.6 %)
than in Asia and Africa (0.83.1 %) [12].
More recently, a 60-country study showed consistent cross-national associations
between the presence of comorbid medical conditions and 12-month MDE preva-
lence, with a mean of 3.2 % in people without comorbidity and 9.323 % in people
with comorbid conditions [13]. Recent results from WHO World Mental Health
Surveys allow comparisons between 12-month prevalence of MDE in high-income
countries and LMICs. Differences were not pronounced. The 12-month age-adjusted
prevalence was 5.5 % in high-income countries and 5.9 % in LMICs. Screening
prevalence in the surveys was also similar: 10.6 % in high-income countries and
10.5 % in LMICs [16], suggesting that the diagnostic approach was not biased.
However, the association between mental health disorders and days out of role, a
measure of disability, was quite variable, suggesting differences in the impact of
symptoms and availability of treatment. Indeed, the surveys suggest most mental
health disorders go untreated. Even in high-income countries, serious mental health
disorders went untreated in about half the cases [14].
In the mental health surveys, anxiety and depressive disorders were more preva-
lent than impulse-control and substance abuse disorders. This association was also
consistent across countries grouped by income. Country-level surveys in a variety
of settings, from primary care to door-to-door targeted populations, confirm the

WHO estimates of 12-month prevalence and show robust associations between risk
of major depressive episodes and social disadvantage, stressful life events, and
comorbid disease. Some recent examples include a 10/66 Dementia Research Group
survey of Peru, Mexico, and Venezuela [15], the Sao Paulo Ageing and Health
Survey [16], and an urban primary care study from China [17]. Increasing information
about risk factors and correlates of poor mental health in LMICs is also becoming
available for the first time, such as a population-based survey of suicide mortality in
India [18].
Assessing the burden of mental ill health is a challenge, but a consistent body of
research suggests it is substantial by every benchmark. The Global Burden of
Disease Study examined incidence, prevalence, duration, and case fatality for 107
conditions and 483 disabling consequences of disease [19]. These estimates were
used to develop the disability-adjusted life year (DALY), a summary measure of
population health. DALYs are lost years of healthy life due to disease and combined
loss of life and life lived with disability. By this metric, mental health disorders
carry a disease burden as high as cardiovascular and respiratory diseases. Mental
disorders were associated with a greater burden than the cancers or HIV because of
their prevalence, early age of onset, lifelong duration, lack of effective therapy, and
severe disability.
In 2005, mental, neurological, and substance abuse (MNS) disorders were respon-
sible for about 13.5 % of global disease burden. Among the noncommunicable dis-
eases (the source of half of global disease burden), MNS were responsible for 28 %
of global burden [20]. By 2030, global disability due to MNS will increase to 14.4 %.
Importantly, between 2005 and 2030, LMICs will see an increase in disease burden
due to MNS. In low-income counties, the proportion of disease burden associated
with MNS will increase from 9.1 to 11 % [20].
Unipolar depression is the third most prominent cause of global disease burden
[21]. Among the MNS, unipolar depression is currently responsible for about 65.5
million DALYs worldwide. It is followed by alcohol-use disorders (23.7 million),
schizophrenia (16.8 million), bipolar disorder (14.4 million), Alzheimers disease and
the dementias (11.2 million), drug-use disorders (8.4 million), epilepsy (7.8 million),
migraine (7.8 million), and panic disorder (7.0 million). In both high-income coun-
tries and LMICs, unipolar depression is first among the MNS in disease burden.
Given the high prevalence of MNS and their substantial disease burden, it is sur-
prising that about a fifth of countries allocate less than 1 % of their health budgets to
mental health care [22]. In fact, the mismatch may be even greater as we recognize
the effect of MNS on risk of disability in other family members. For example, an
increasing body of research has shown that maternal depression increases risk of
underweight and stunted growth in children [20]. Spillover morbidity and disability
among family members is likely to be important in late-life depression as well.
Lay populations appear to recognize the disabling quality of mental health disorders.
In the WHO World Mental Health Surveys, participants from high-income countries
and LMICs both reported greater disability from mental health conditions than
physical conditions [23].
11.4 Global Perspectives: Recognition of Depressive

Disorders
11.4.1 Somatization
Somatic presentation of depressive symptoms is common. In a German study, patients

with coexisting depressed mood and physical disease visited the doctors practice
significantly more often than other individuals [24]. An Austrian study among Turkish
immigrants showed that they scored significantly higher in somatic symptoms (head-
ache, backache, and dry mouth) than Turkish patients seeing physicians in Turkey
[25]. In the same manner, studies among Chinese, Indian, and Malay patients found
that depression is more likely in elderly patients with multiple medically unexplained
somatic symptoms [26, 27]. These findings suggest that somatic symptoms in the
presentation of depressive disorders may be more important in LMIC populations.
Mental health training in LMICs could profitably stress recognition of somatization in
depression. Research involving older populations in LMIC is needed to determine if
somatic presentation is typical in older populations as well.
11.4.2 Stigma
Stigma regarding mental illness is associated with greater psychiatric symptom

severity and reduced treatment adherence [28]. Higher levels of internalized stigma
are associated with lower levels of hope, empowerment, self-esteem, self-efficacy,
quality of life, and social support. In the United States, depressed older adults
endorsed a high level of public stigma, which lowered the likelihood of seeking
mental health treatment [29]. African-American older adults in the United States
were more likely to internalize stigma and endorsed less positive attitudes toward
seeking mental health treatment than White elders. In the same manner, Asian-
Americans and Latinos expressed greater shame and embarrassment about having a
mental illness than Whites. Asian-Americans also expressed greater difficulty in
seeking or engaging in mental health treatment [30].
Israeli elderly participants who reported stigmatization scored consistently
higher in the depressed mood and lower in self-esteem than those without stigmati-
zation [31]. Stigma is a feature of alienation, perceptions of being devalued as a
member of society, and is common in schizophrenia as well [32]. A recent study
among adults of 13 European countries showed that self-stigma occurs among
approximately one in five people with bipolar disorder or depression [33]. Elements
of internalized stigma include alienation, endorsement of mental illness stereotypes,
social withdrawal, and actual or perceived discrimination.
Direct contact with people who have mental disorders is an effective way to alter
public attitudes toward mental illness [34, 35]. Consumer reports of their experience
with mental health problems and their contact with service providers had the greatest
and most lasting impact on reducing mental health stigma [35]. Public campaigns,
such as New Zealands Like Minds, Like Mine, use stories of famous people
who have experienced mental illness to create awareness and improved attitudes
among the general public [36]. A British study examined national trends associated
with the implementation of the Time to Change program and reported increases
in positive attitudes among the English population [37]. These findings stress
the importance of global efforts to reduce stigma and discrimination against mentally
ill patients.
11.5 Global Perspectives on Treatment and Prevention

of Depressive Disorders
11.5.1 Enhancing Knowledge of MNS in Primary Care
Older adults are more likely to be treated for depression in primary care settings
[38, 39]. Meta-analytic reviews suggest that primary care physicians are accurate in
recognizing depression only about half the time, both in younger and older adults
[40]. Better detection of depression may be possible with the use of quick diagnos-
tic tools in primary care settings but because of high false-positive rates should only
be used when sufficient resources for second-stage assessment are available for
screen positives [41]. Efforts should be invested for fine-tuning and developing brief
diagnostic tools.
11.5.2 Task Shifting, Task Sharing
The shortage of mental health specialists in LMICs requires task shifting or task
sharing using volunteers or staff who may not have advanced training in mental
health [42, 43]. The success of this approach was demonstrated in the MANAS trial
(Project to Promote Mental Health in the local language, Konkan) conducted in
Goa, India [44]. Lay health counselors taught patients strategies to alleviate symp-
toms, such as breathing exercises for anxiety symptoms, scheduling activities for
symptoms of depression, and adherence management for patients receiving antide-
pressants. They also provided information about social and welfare organizations
when needed. The randomized controlled trial (RCT) demonstrated successful
reductions in depression and anxiety symptoms through the use of lay health coun-
selors as part of a collaborative stepped-care intervention in public clinics. These
findings are encouraging since 40 % of participants were aged 50 or older. Subsequent
analyses of MANAS suggest cost-effectiveness [45] and benefits clearest in public
rather than private clinics [44].
As shown in MANAS, lay health counselors can undertake several health-care
roles, are fairly low cost to train, and are readily available in developing countries.
This approach follows successful task-sharing efforts in LMICs for delivery of HIV
services and a range of maternal and child health interventions. This evidence
should be used to improve services for common mental disorders in settings for
which mental health professionals are limited. The evidence base for use of
nonspecialist mental health-care personnel in collaborative care is growing,

with studies showing effective interventions in Uganda [46], Pakistan [47], and
Chile [48], though these have not focused on older adults. Developing models of
depression prevention in older adults via lay delivery systems may be important for
practice and policy in high-income countries as well.
11.5.3 Preventing Downstream Consequences of Depression
Prevention also entails protecting older adults from the downstream consequences
of depression, which range from poor medication adherence and excess disability
to suicide [42]. The Prevention of Suicide in Primary Care Elderly: Collaborative
Trial (PROSPECT) showed that depression care management strategies can reduce
suicidal ideation by about half. In cases where depression cannot be prevented,
good management can still reduce much of the disease burden associated with the
condition.
11.5.4 Prevention of Depressive and Anxiety Disorders
Prevention of depressive disorders is of great public health significance in LMICs as

well as high-income countries [49]. A recent RCT from the Netherlands suggests
that prevention of late-life depression in primary care settings is feasible and cost-
effective [50]. Patients with subthreshold symptoms were offered either a preven-
tive stepped-care program or usual care. The stepped-care program included
watchful waiting, cognitive behavioral therapy-based bibliotherapy, problem-
solving therapy, and referrals to primary care if the patient needed antidepressant
medication. The incidence of major depressive episodes and anxiety disorders was
reduced by half over a 1-year follow-up, 11 % versus 24 %.
11.6 Potential for Impact on Global Mental Health
Providing mental health services in LMICs is cost-effective. A WHO study [51]

conducted in Nigeria, Estonia, and Sri Lanka showed that even fairly low-cost men-
tal health interventions offer substantial benefit. Interventions for common mental
disorders (such as depression and panic disorder) were found to be highly cost-
effective, such that each DALY averted costs less than 1 year of average per capita
income, one threshold used in cost-effectiveness studies. Community-based inter-
ventions for more severe mental disorders (using antipsychotic and mood-stabilizing
drugs) still met the criterion of cost-effectiveness (with each DALY averted costing
less than three times the average annual income). The authors concluded that there
is just as much of an economic rationale for investing in mental health as there is in
other chronic, non-communicable diseases. However, they also determined that
hospital-based treatment of mental disorders or use of newer antipsychotic drugs is
not a cost-effective use of resources in LMICs.
If the interventions are cost-effective, the question then is what is required to

deliver such services in LMICs. What would it take for countries that currently
invest less than 1 % of their health budgets for mental health services to invest a
minimum of 510 %, as the WHO report [51] recommends? A number of organiza-
tions have responded to this call and have begun to lay the groundwork for a global
response to the gap in mental health services.
One approach builds on the MANAS model and recommends expansion of
collaborative care for depression to include multi-condition collaborative care [52].
As LMICs build services to address noncommunicable diseases, they have an oppor-
tunity to include mental health services in packages of care. They may also use
models developed in one setting (e.g., directly observed therapy in tuberculosis) for
psychiatric care (directly observed therapy for patients with schizophrenia) [53].
More generally, the treatment gap in mental health disorders is increasingly a
focus of research and intervention. A World Psychiatry Association survey has iden-
tified these priorities [54]. Among older adults, key gaps include dementia and
depression care in both high-income countries and LMICs. Recommended interven-
tions across countries differ only in pharmacotherapy because of the higher cost of
newer therapies. Models for closing the gap have been proposed by nongovernmen-
tal organizations, such as BasicNeeds [55], and are the focus of RCTs, such as the
PRogramme for Improving Mental health carE (PRIME) [56]. PRIME will evaluate
the impact of mental health service in primary care in a low-resource area in each of
the five countries (Ethiopia, India, Nepal, South Africa, and Uganda). It will then
evaluate scaling up of these models of care to other districts within the countries.
This pivotal effort will be very valuable for future efforts in global mental health and
is consistent with consensus from expert panels [42, 43].
Acknowledgments Supported in part by P30 MH90333, NIMH Advanced Center for Interventions
and Services Research-Late Life Mood Disorders, University of Pittsburgh.
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Index
A Blacks, late life

ACE. See Angiotensin-converting enzyme age-linked life stages, 154
(ACE) depressive symptoms, ethnicity, nativity
AFrica Focus on Intervention Research for and gender, 164165
Mental health (AFFIRM), 175 ethnicity and nativity, depressive
African Americans symptoms, 161, 163164
age, 157 general patterns of, 155
depressive symptoms, 165 implications, 165168
MDE, 159 measures
NSAL adult sample, 159 analytical strategy, 161
prevalence rates, 156 depressive symptoms, 160161
self-identification, 159 MDD and MDE, 160
sociodemographic characteristics, 160 sociodemographic characteristics, 160
socioeconomic status, 156 sample, 159160
Age-related macular degeneration (AMD), 115 US-and foreign-born Blacks
Alameda County Study, 27, 37 correlates of depression, 156157
Alzheimers disease (AD), 26, 63, 66 depression rates, Black samples, 156
AMD. See Age-related macular degeneration NSAL, 159
(AMD) symptoms and subthreshold depression,
American College of Physicians, 139 157158
American College of Preventive Medicine, 139 within-group differences, 154
American Psychiatric Association, 34 Brain-derived neurotrophic factor (BDNF),
-Amyloid, 63 37, 70
Angiotensin-converting enzyme (ACE), 71 Brief Behavioral Treatment for Insomnia
Antidepressant monotherapy, 69 (BBTI), 3
B C
BasicNeeds, 181 Cardiovascular risk factors (CVRFs), 26
BBTI. See Brief Behavioral Treatment for Caribbean Blacks
Insomnia (BBTI) CES-D scores, 163
BDNF. See Brain-derived neurotrophic factor marriage, 157
(BDNF) NSAL adult sample, 159
Beck Depression Inventory (BDI), 90, 106, 122 physical illness and disability, 157

Aging Medicine 9, DOI 10.1007/978-3-319-16045-0
186 Index
Caribbean Blacks (cont.) Default-mode network, 62

prevalence rates, 156 Delivery System Design, 48
psychosocial stressors, 167 Dementia, 6, 9, 26, 62, 64, 66, 71, 89, 145,
self-identification, 159 166, 177, 181
sociodemographic characteristics, 160 Depression
socioeconomic status, 156 antidepressant medications, 3
CAT. See Computerized adaptive testing (CAT) BBTI, 3
CBT. See Cognitive behavior therapy (CBT) biosignatures research, 4
Center for Epidemiological Studies- blood-based measures, 3
Depression Scale (CES-D), 26, 84, in elderly, 9
85, 89, 121, 122, 128, 139, 160, environmental factors, 8
161, 164166 epidemiological modeling, 3
Centers for Medicare and Medicaid Services learning-based psychotherapies, 2
(CMS), 139 LMICs, 2
Cerebrovascular disease, 58, 124 MANAS trial, 2
CES-D. See Center for Epidemiological mRNA transcriptome patterns, 4
Studies-Depression Scale (CES-D) personal loss, 8
Changing Lives of Older Couples study, 24 preventive interventions, 3
CHIRMH. See Collaborative Hubs for psychological factors, 8
International Research on Mental Depression Endpoint Prevention in the
Health (CHIRMH) VITamin D and OmegA-3 TriaL
Chronic care model, 48 (VITAL-DEP), 129
CIDI. See Composite International Diagnostic Depressive disorders
Interview (CIDI) depression screening and assessment
Clinical Information Systems, 48 late-life depression screening tools,
Clock Drawing Test, 71 139140
CMS. See Centers for Medicare and Medicaid policies, 138139
Services (CMS) later life
Cognitive behavior therapy (CBT), 3, 104, Global Burden of Disease Studies,
105, 122, 141 137138
Collaborative Hubs for International Research United States and Worldwide,
on Mental Health (CHIRMH), 175 136137
Collaborative Psychiatric Epidemiology primary prevention, cost-effectiveness of
Surveys (CPES), 156, 158, 159 cost-benefit analyses of, 142144
Community Resources, 48 first case/first onset, late-life
Compliance, 14 depression, 140141
Composite International Diagnostic Interview secondary prevention, cost-effectiveness of
(CIDI), 92, 160, 162, 176 cost-benefit analyses of, 147149
Comprehensive Meta-Analysis software, 106 recurrence of late-life depression/
Computerized adaptive testing (CAT), 93, 94 worsening of depression, 145146
Coping with Depression course (CWD), 101102 Depressive symptoms
Cornell Scale for Depression in Dementia, 140 assessments
Corticotropin-releasing hormone (CRH), 37 CIDI, 92
CPES. See Collaborative Psychiatric DIS, 92
Epidemiology Surveys (CPES) DSM, 92
CVRFs. See Cardiovascular risk factors (CVRFs) ICD, 92
CWD. See Coping with Depression course mental health research, 91
(CWD) MINI, 92
SCID, 92
SDS, 93
D measures and screeners
D-allele carriers, 71 anhedonia, 85
DALY. See Disability-adjusted life year (DALY) BDI, 90
Decision Support, 48 CES-D, 84
Index 187
depression scales, diagnostic gold Global Alliance for Chronic Diseases

standards, 8688 (GACD), 175, 176
evaluation and screening measures, 85 Global Burden of Disease Study, 177
GDS, 89 Global Consortium for Depression Prevention, 4
Likert-style and binary (yes/no) Global Mental Health-Map (GMH-Map), 176
formats, 84
MDD, 89
MDS 3.0, 91 H
older adults, 85, 89 HADS. See Hospital Anxiety and Depression
PHQ-9, 90 Scale (HADS)
reliability, 84 Hamilton Depression Rating Scale, 40
somatic symptoms, 89 Haplotype-tagging single nucleotide
validity, 90 polymorphism (htSNP) analysis, 71
Diagnostic and Statistical Manual of Mental Health and Retirement Study, 23, 37
Disorders (DSM), 34, 89, 90, 92 Health Care Organization, 48
Diagnostic Interview Schedule (DIS), 92 Hopelessness theory, 38
Diathesis stress model, 36 Hospital Anxiety and Depression Scale
Diffusion tensor imaging (DTI), 59, 64 (HADS), 40, 141
Disability-adjusted life year (DALY), 135, 177 Hypothalamic-pituitary-adrenal (HPA)
Doppler ultrasound, 69 axis, 37
Dorsolateral prefrontal cortex (DLPFC), 60
DSM. See Diagnostic and Statistical Manual
of Mental Disorders (DSM) I
DTI. See Diffusion tensor imaging (DTI) ICD. See International Classification of
Dysthymia, 73, 137, 145 Diseases (ICD)
Improving Mood-Promoting Access to
Collaborative Treatment (IMPACT)
E trial, 130
Enhancing Recovery in Coronary Heart IMT. See Intima-media thickness (IMT)
Disease (ENRICHD), 39 Incremental cost-effectiveness ratio (ICER),
Epidemiologic Catchment Area (ECA), 35, 140, 141, 145
92, 156 Indicated prevention
Experience Corps (EC) program, 49 CWD, older adults
behavioral activation approach, 101
cognitive skills, 101
F environmental changes, 102
Female gender, 23 psychoeducational treatment, 101
FIT. See Functioning Improvement Tool (FIT) social learning theory, 102
fMRI. See Functional Magnetic Resonance toolbox idea, 101
Imaging (fMRI) internet-based CBT, 104
Fractional anisotropy (FA), 59 IPC, 103
Framingham Stroke Risk Profile scale, 60 life review and reminiscence, 103104
Franklins maxim, 34 major depressive disorders, 100
Functional Magnetic Resonance Imaging older adults
(fMRI), 6062, 67 depressive episode, 107
Functioning Improvement Tool (FIT), 122 effect sizes, 106
Hedgess g, 106
Internet-based intervention, 107
G intervention effects, 108
GACD. See Global Alliance for Chronic NNT, 106
Diseases (GACD) psychological treatment and
Geriatric Depression Scale (GDS), 40, 89, 90, depression, 105
122, 123, 139, 140 Research Diagnostic Criteria, 105
Geriatric depression syndrome, 63 Risk of bias assessment tool, 106
188 Index
Indicated prevention (cont.) L

PST, 103 Late-life depression (LLD)
stepped-care models, 104105 health policy and economic aspects
subclinical depression, 100 (see Depressive disorders)
Institute of Medicine (IOM), 7 IOM Framework, 7
late-life depression, 129130 measurements and assessments
selective prevention (see Depressive symptoms)
AMD, 115 selective prevention
clinical trials, 115 (see Selective prevention)
comprehensive interdisciplinary care social and behavioral risk factors
intervention vs. simple (see Social and behavioral risk
interdisciplinary care, 121 factors)
EPA and DHA active treatment alcohol drinking behavior, 27
groups, 123 caregiving burden, 26
escitalopram, 115 CES-D, 26
GDS, 122 CVRFs, 26
inadequate evidence, 114 demographic factors, 2324
Individualized Cognition-Action female gender and spousal loss, 20
program, 122 leisure-time activities, 29
nursing home setting, 122 marital bereavement, 24
physical impairments, 121 Mediterranean dietary pattern, 27
placebo control, 115 metabolic syndrome, 29
provider awareness, lack of, 114 physical activity and adherence, 27
PST, 115 potential risk factors/risk markers, 20
randomized trials, 116120 smoking behavior, 27
risk factor assessment, 114 social isolation, 26
social isolation preventive intervention social support, 27
program, 122 sociodemographic risk factors, 25
vitamin/nutrient interventions, 123 sub-threshold/sub-clinical affective
universal prevention symptoms, 20
edcational intervention, 129 syndromal depression, 24
folic acid/B vitamins, 124 state vs. scar effects, 67
low-incidence disorders, 123 universal prevention (see Universal
Mediterranean diet, 128 prevention)
pharmacologic interventions, 124 vascular depression (see Vascular
PREDIMED trial, 128 depression hypothesis)
randomized trials, 125127 vascular disease and depression
SEAL, 124 disconnection, 68
WAFACS, 128 hypoperfusion, 6869
WHI-CaD, 128 inflammatory processes, 6970
Institute of Medicines lexicon, 3 Latin America Treatment and Innovation
Interferon-induced depression, 34 Network in Mental Health
Interleukin-6 (IL-6), 69 (LATIN-MH), 175
International Classification of Diseases Lifetime psychiatric disorders, 35
(ICD), 92, 105 LLD. See Late-life depression (LLD)
International Classification of Functioning, Loneliness, 9
Disability and Health Low-and middle-income countries
(ICIDH-2), 35 (LMICs), 2
Interpersonal counseling (IPC), 103 depressive disorders
Interpersonal psychotherapy and anxiety disorders, 180
(IPT), 103 downstream consequences, 180
Intima-media thickness (IMT), 68 primary care settings, MNS, 179
IOM. See Institute of Medicine (IOM) somatization, 178
Index 189
stigma, 178179 prevention intervention, 47

task shifting and task sharing, 179180 selective prevention trials, 40, 47
global mental health, 180181 trial design and interpretation, 4748
global perspective Mental Health Gap Action Programme
AFFIRM, 175 (mhGAP), 174
CHIRMH, 175 Mental, neurological and substance abuse
chronic noncommunicable diseases and (MNS), 177
mental health, 173 Mild Cognitive Impairment (MCI), 62
disparities, 173 Mini-International Neuropsychiatric Interview
GACD, 175 (MINI), 92
GMH-Map, 176 Minimum Data Set (MDS) assessments, 91
Lancet Global Health, 176 Montgomery-Asberg Depression Rating
LATIN-MH, 175 Scale, 140
mhGAP, 174 Mynors-Wallis method, 103
NIMH, 175 Myocardial infarction (MI), 2, 38, 39, 123
PaM-D, 175
PLoS Medicine, 176
public education, 176 N
SHARE, 175 National Health and Nutrition Examination
World Bank, 172 Survey (NHANES), 136
mental, neurological and substance abuse, National Health Interview Survey, 36
176177 National Institute of Mental Health (NIMH),
159, 175
National Institutes of Health (NIH), 93, 175
M National Survey of American Life (NSAL),
Magnetic transfer resonance (MTR) imaging, 60 158160, 162, 167
Major depressive disorder (MDD), 26, 89, NHANES. See National Health and Nutrition
90, 129, 137, 145, 155, 159161, Examination Survey (NHANES)
163, 166 NIMH. See National Institute of Mental
Major depressive episode (MDE), 155, Health (NIMH)
159161, 163, 166, 176 Number-needed-to-treated (NNT), 11, 71, 106
Maladaptation, 37
MANAS model, 181
MANAS trial, 2 O
Manual-based coping strategy program, 145 Older adults
Markov models, 140 CWD
MCI. See Mild Cognitive Impairment (MCI) behavioral activation approach, 101
MDD. See Major depressive disorder (MDD) cognitive skills, 101
MDE. See Major depressive episode (MDE) environmental changes, 102
Mean diffusivity (MD), 59 psychoeducational treatment, 101
Medical comorbidity social learning theory, 102
depression, prevention of, 34 toolbox idea, 101
indicated prevention trials, 40 internet-based CBT, 104
mortality and depression, 39 IPC, 103
opportunities, 4849 life review and reminiscence, 103104
physical health and depression PST, 103
adverse drug effects, 38 stepped-care models, 104105
disability, 3536
hopelessness, 38
loneliness, 3738 P
pain, 36 Parkinson disease, 6
risk behaviors, 37 Partnership for Mental Health Development
stress, 3637 (PaM-D), 175
190 Index
Patient Health Questionnaire (PHQ), 90, 91, SCID. See Structured Clinical Interview for
129, 139 DSM Disorders (SCID)
Patient Reported Outcomes Measurement SDS. See Sheehan Disability Scale (SDS)
Information System (PROMIS), 93 Selective prevention
Pittsburg-compound B (PiB), 63 AMD, 115
Population attributive fraction (PAF), 10 clinical trials, 115
Positron Emission Tomography (PET), 63 comprehensive interdisciplinary care
Poststroke depression, 34 intervention vs. simple
Prevention framework interdisciplinary care, 121
indicated prevention model, 12 EPA and DHA active treatment
population at-risk, 911 groups, 123
psychiatry, 56 escitalopram, 115
risk factors, 89, 13 GDS, 122
selective prevention model, 12 inadequate evidence, 114
types, 78 Individualized Cognition-Action
Prevention of Suicide in Primary Care Elderly program, 122
Collaborative Trial (PROSPECT), nursing home setting, 122
39, 130, 180 physical impairments, 121
Primary Care Evaluation of Mental Disorders placebo control, 115
(PRIME-MD), 90 provider awareness, lack of, 114
Problem-solving therapy (PST), 3, 73, 103, PST, 115
115, 145 randomized trials, 116120
PRogramme for Improving Mental health carE risk factor assessment, 114
(PRIME), 181 social isolation preventive intervention
PROMIS. See Patient Reported Outcomes program, 122
Measurement Information System vitamin/nutrient interventions, 123
(PROMIS) Selective serotonin reuptake inhibitors
PROsetta Stone, 94 (SSRIs), 47, 63, 71
PST. See Problem-solving therapy (PST) Self-Management, 48
Senile macular degeneration, 34
Serotonergic system, 63
Q Sertraline Antidepressant Heart Attack
Quality-adjusted life year (QALY), 140 Randomized Trial (SADHART), 39
SES. See Socioeconomic status (SES)
Sheehan Disability Scale (SDS), 93
R Social and behavioral risk factors
Randomized controlled trial (RCT), 115, 124, demographic factors, 2324
128, 129, 136, 141, 145, 179, 180 female gender and spousal loss, 20
Regional homogeneity (ReHo), 62 late-life depression risk
Reninangiotensin system (RAS), 70 alcohol drinking behavior, 27
Resources for Enhancing Alzheimers caregiving burden, 26
Caregiver Health (REACH) II CES-D, 26
randomized trial, 26 CVRFs, 26
Reykjavik Study, 23 leisure-time activities, 29
Rotterdam study, 69 marital bereavement, 24
Mediterranean dietary pattern, 27
metabolic syndrome, 29
S physical activity and adherence, 27
SADHART. See Sertraline Antidepressant smoking behavior, 27
Heart Attack Randomized Trial social isolation, 26
(SADHART) social support, 27
Safety, evidence for efficacy, acceptability and sociodemographic risk factors, 25
low cost (SEAL), 124 syndromal depression, 24
Index 191
potential risk factors/risk markers, 20 memory, 6566

sub-threshold/sub-clinical affective processing speed, 66
symptoms, 20 white matter disruption, 64
Socioeconomic status (SES), 23, 154 functional neuroimaging studies
South Asian Hub for Advocacy, Research and PET, 63
Education (SHARE) on mental resting state fMRI, 6162
health, 175 task-related fMRI, 6061
SSRIs. See Selective serotonin reuptake genetics, 7071
inhibitors (SSRIs) morphological studies
Stepped-care models, 104105 white matter lesions, 5859
Stress vulnerability model, 8 white matter tracts, 5960
Structured Clinical Interview for DSM treatment strategies
Disorders (SCID), 92 antidepressants, 72
Subgenual anterior cingulate gyrus cognitive impairment, 71
(sgACG), 61 NNT, 71
Syndromal depression, 24 PST, 73
psychotherapeutic interventions, 73
Veterans Affairs (VA) Medical Centers, 139
T
Taylor expansion approximation
technique, 161 W
Tricyclic antidepressants (TCAs), 71 WAFACS. See Womens Antioxidant and
Folic Acid Cardiovascular Study
(WAFACS)
U Wagner model, 48
Unipolar depressive disorders, 136 White matter hyperintensities (WMH), 58
Universal prevention White matter lesion (WML), 5859
edcational intervention, 129 WHO. See World Health Organization (WHO)
folic acid/B vitamins, 124 Womens Antioxidant and Folic Acid
low-incidence disorders, 123 Cardiovascular Study
Mediterranean diet, 128 (WAFACS), 128
pharmacologic interventions, 124 Womens Health Initiative Calcium and
PREDIMED trial, 128 Vitamin D (WHI-CaD) Trial, 128
randomized trials, 125127 World Federation of Neurology, 173
SEAL, 124 World Health Organization (WHO), 35, 92,
WAFACS, 128 135, 136, 174177, 180
WHI-CaD, 128 World Health Organization Disability
US Preventive Services Task Force Assessment Scale, 73
(USPSTF), 139 World Health Organization Mental Health
Atlas, 173
World Health Survey, 35
V World Mental Health Day, 175
Val66Met polymorphism, 70 World Psychiatry Association, 181
Vascular depression hypothesis
cognition
executive functioning, 6465 Y
LLD and risk of dementia, 66 Years lived with disability (YLD), 136

Prevention of Late Depression

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Aging Medicine

Series Editors: Robert J. Pignolo Mary Ann Forciea Jerry C. Johnson

More information about this series at http://www.springer.com/series/7622

Library of Congress Control Number: 2015935617

Springer Cham Heidelberg New York Dordrecht London

Printed on acid-free paper

Humana Press is a brand of Springer

Boston, MA, USA Olivia I. Okereke, M.D., M.S.

1 Prevention of Major Depression: A Global Priority ............................ 1

11 Global Priorities and Possibilities.......................................................... 171

Index ................................................................................................................. 185

Steven M. Albert Department of Behavioral and Community Health Sciences,

Elisabeth Duursma Department of Education, University of Wollongong,

C.F. Reynolds III, M.D. (*)

Springer Science+Business Media New York 2015 1

Prevention of common mental disorders, particularly major depression, represents

neurotrophic factor, psychosocial stressors, and vascular comorbidity. We note in

2.1 Introduction: Prevention in Psychiatry

R.A. Schoevers (*)

Springer Science+Business Media New York 2015 5

2.2 Types of Prevention

Prevention differs from intervention and treatment as it is aimed at general popula-

2.3 Risk Factors

Table 2.1 Risk factors depression among elderly

2.4 Identification of the Population At-Risk

When initiating and testing the effectiveness of indicated prevention, it is essential

2.5 What Interventions Work Best?

Fig. 2.1 Selective prevention model

2.6 Critical Remarks

Although prevention programs could reduce the incidence of late-life depression,

Springer Science+Business Media New York 2015 19

Mental other factors were not significantly

Study authors Study Risk factors Depression

3.2 Demographic Factors and Late-Life Depression Risk

Groffen et al. [6] recently conducted an investigation among a sample of 4,809

3.3 Social Factors and Late-Life Depression Risk

Table 3.3 Studies of sociodemographic risk factors and late-life depression

levels of depressive symptoms than white non-

Finally, social support has been identified as important to late-life depression

3.4 Lifestyle/Behavioral Factors and Late-Life

Study authors Study Risk factors Depression

3.5 Future Directions

As noted above, an important future direction in addressing social and behavioral

Study authors Study Risk factorsDepression

L. Dong J.J. Gallo M.D., M.P.H. (*)

Springer Science+Business Media New York 2015 33

4.1 Laying the Groundwork for Prevention

4.2 The Intersection of Physical Health and Depression

Disability is defined by the International Classification of Functioning, Disability

Fig. 4.1 Conceptual framework linking physical and mental health

4.2.4 Risk Behaviors

Loneliness is the perceived isolation from ones surrounding relationships.

Hopelessness is a key concept of major depression [54], and also an independent

4.2.7 Adverse Drug Effects

Due to age-related changes in pharmacokinetics and pharmacodynamics, older

4.3 Mortality and Depression

4.4 Evidence on Prevention of Depression in Medical

We carried out a literature review to identify prevention intervention trials with a

4.4.1 Indicated Prevention Trials

4.4.2 Selective Prevention Trials

Table 4.1 Indicated and selective prevention studies

dysthymia physicians regarding achieving depression remission in the intervention

based on HAM-D6 (9) was 11.5 % in the

in the intervention group were (P = 0.04)