Mood Disorder Guide

Mood Disorders
Jean-Claude André Yazbek, MD

Mood Disorders: Introduction
• Mood is a pervasive and sustained emotional
tone that influences behaviors and thoughts.
• Disorders of mood, also called affective
disorders, are common among the general
population. They include depressive disorder,
bipolar disorder, and other disorders.
• Patients with only major depressive episodes
are said to have major depressive disorder or
unipolar depression.
[Kaplan and Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry (2014) B. Sadock, V. Sadock and
P. Ruiz.]
Mood Disorders: History
• The story of King Saul as depicted by The Old
Testament describes a depressive syndrome: Saul was
at times possessed by an “evil spirit” which “tormented
him”. He had several symptoms such as insomnia,
feelings of worthlessness, indecisiveness and even
paranoia and irritability. He may have committed
suicide during a battle.
• About 400 BC, Hippocrates used the terms mania and
melancholia to describe mental disturbances.
• Around 30 AD, Celsus described melancholia (from
Greek melan [“black”] and chole [“bile”]) as a
depression caused by black bile.
P. Ruiz.]
Mood Disorders: History-2
• In 1854, Jules Falret described a condition called folie
circulaire, in which patients experience alternating moods of
depression and mania.
• In 1882, the German psychiatrist Karl Kahlbaum, using the
term cyclothymia, described mania and depression as stages
of the same illness.
• In 1899, Emil Kraepelin described manic-depressive
psychosis using most of the criteria that psychiatrists now
use to establish a diagnosis of bipolar I disorder.
• According to Kraepelin, the absence of a dementing and
deteriorating course in manic-depressive psychosis
differentiated it from dementia precox (as schizophrenia was
then called)
P. Ruiz.]
The DSM-5 Classification of Mood Disorders
• Section II, Chapter 3 (pages 123-154):

Bipolar and Related Disorders.
• Section II, Chapter 4 (pages 155-188):
Depressive Disorders.
[Diagnostic and Statistical Manual of Mental Disorders. 5 th Edition. 2013. American Psychiatric Association]
• Section II, Chapter 3: Bipolar and Related

Disorders.
• Section II, Chapter 4: Depressive
Disorders.
The DSM-5 Classification of Depressive Disorders
• Disruptive Mood Dysregulation Disorder
• Major Depressive Disorder
• Persistent Depressive Disorder
• Premenstrual Dysphoric Disorder
• Substance/Medication-Induced Depressive
Disorder
• Depressive Disorder Due to Another Medical
Condition
• Other Specified Depressive Disorder
• Unspecified Depressive Disorder
Disorder
Condition
Famous Individuals with Depression: Charles
Baudelaire
• He referred to it as spleen
• Also suffered from substance use disorders
Famous Individuals with Depression: Charles Baudelaire
Spleen
Quand le ciel bas et lourd pèse comme un couvercle
Sur l'esprit gémissant en proie aux longs ennuis,
Et que de l'horizon embrassant tout le cercle
II nous verse un jour noir plus triste que les nuits;
• Quand la terre est changée en un cachot humide,
Où l'Espérance, comme une chauve-souris,
S'en va battant les murs de son aile timide
Et se cognant la tête à des plafonds pourris;
• Quand la pluie étalant ses immenses traînées
D'une vaste prison imite les barreaux,
Et qu'un peuple muet d'infâmes araignées
Vient tendre ses filets au fond de nos cerveaux,
• Des cloches tout à coup sautent avec furie
Et lancent vers le ciel un affreux hurlement,
Ainsi que des esprits errants et sans patrie
Qui se mettent à geindre opiniâtrement.
• Et de longs corbillards, sans tambours ni musique,
Défilent lentement dans mon âme; l'Espoir,
Vaincu, pleure, et l'Angoisse atroce, despotique,
Sur mon crâne incliné plante son drapeau noir.
Famous Individuals with Depression: Charles Baudelaire
• Spleen
When the cold heavy sky weighs like a lid
On spirits whom eternal boredom grips,
And the wide ring of the horizon's hid
In daytime darker than the night's eclipse:
• When the world seems a dungeon, damp and small,

Where hope flies like a bat, in circles reeling,
Beating his timid wings against the wall
And dashing out his brains against the ceiling:
• When trawling rains have made their steel-grey fibres

Look like the grilles of some tremendous jail,
And a whole nation of disgusting spiders
Over our brains their dusty cobwebs trail:
• Suddenly bells are fiercely clanged about

And hurl a fearsome howl into the sky
Like spirits from their country hunted out
Who've nothing else to do but shriek and cry —
• Then long processions without fifes or drums

Wind slowly through my soul. Hope, weeping, bows
To conquest. And atrocious Anguish comes
To plant his black flag on my drooping brows.
Famous Individuals with Depression: Woody Allen
• Fought depression with humor and

creativity.
• “My whole life I am constantly
fighting all kinds of depression
and terror and anxiety”.
• Spent nearly 40 years in
psychoanalysis.
Major Depressive Disorder:
DSM-5 Diagnostic Definition
A. Five (or more) of the following present during a 2-week period; at least one is either
(1) depressed mood or (2) loss of interest or pleasure.
(1) Depressed mood most of the day, nearly every day, as indicated by either subjective
report (e.g., feels sad, empty, hopeless) or observation made by others (e.g., appears
tearful). (Note: In children and adolescents, can be irritable mood.)
(2) Markedly diminished interest or pleasure in all, or almost all, activities .
(3) Significant weight loss or weight gain, or decrease or increase in appetite nearly every
day.
(4) Insomnia or hypersomnia nearly every day.
(5) Psychomotor agitation or retardation nearly every day.
(6) Fatigue or loss of energy nearly every day.
(7) Feelings of worthlessness or excessive or inappropriate guilt.
(8) Diminished ability to think or concentrate, or indecisiveness.
(9) Recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a
suicide attempt or a specific plan for committing suicide.
Depression Episode:
Depression Episode:
Major Depressive Disorder Specifiers:
With Psychotic Features
• The presence of psychotic features reflects severe disease
and is a poor prognostic indicator.
• A comparison of psychotic vs. nonpsychotic major
depressive disorder indicates that the two conditions may
be distinct in their pathogenesis. One difference is that
bipolar I disorder is more common in the families of
probands with psychotic depression than in the families of
probands with nonpsychotic depression.
• Patients with psychotic depression typically require
antipsychotics in addition to antidepressants; they may also
require ECT.
P. Ruiz.]
With Melancholic Features
• Melancholia is one of the oldest terms in psychiatry, dating back to

Hippocrates (4th century BC); describes the “dark” mood of
depression.
• Still used to refer to a depression characterized by severe
anhedonia, early morning awakening, weight loss, and profound
guilt.
• Common for melancholic patients to have suicidal ideation.
• Melancholic depression can arise in the absence of external life
stressors or precipitants.
• The DSM-5 melancholic features can be applied to major
depressive episodes in major depressive disorder, bipolar I disorder
or bipolar II disorder.
P. Ruiz.]
with Atypical Features
• Presence of specific, predictable characteristics:

– overeating
– oversleeping
• Such symptoms have sometimes been called
“reverse vegetative symptoms”.
• The DSM-5 atypical features can be applied to
depression, bipolar I disorder, bipolar II disorder,
or dysthymic disorder.
P. Ruiz.]
Depression: Case of Kevin
• Kevin, a 15-year-old adolescent, was referred to a
sleep center to rule out narcolepsy.
• His main complaints were fatigue, boredom and a
need to sleep all the time.
• Although he had always started the day somewhat
slowly, he now could not get out of bed to go to
school. That prompted a sleep consultation.
• Formerly a B student, he had been failing most of his
courses in the 6 months before the referral.
• Psychological counseling, predicated on the premise
that his family’s recent move from another city had
led to Kevin’s isolation, was not beneficial.
P. Ruiz.]
• Extensive neurological and general medical workup
findings had proven negative.
• He slept 12 to 15 hours per day but denied cataplexy
(sudden loss of muscle tone especially after
experiencing a strong emotion like surprise), sleep
paralysis and hypnagogic hallucinations.
• During the psychiatric interview, he denied being
depressed but admitted that he had lost interest in
everything except his dog.
• He had no drive, participated in no activities and had
gained 30 pounds in 6 months. He believed that he
was “brain damaged” and wondered whether life was
worth living like that.
P. Ruiz.]
• The question of suicide disturbed him because it was

contrary to his religious beliefs.
• These findings led to the prescription of desipramine
(Norpramin) in a dosage that was gradually increased
to 200 mg per day over 3 weeks.
• Not only did desipramine reverse the presenting
complaints, but it also pushed him to the brink of a
manic episode.
P. Ruiz.]
with Catatonic Features
• Present in several mental disorders, most commonly
schizophrenia and mood disorders. The presence of
catatonia in mood disorders may have prognostic and
treatment significance.
• The hallmark symptoms of catatonia—blunted affect,
extreme withdrawal, negativism, and marked
psychomotor retardation—can be seen in both catatonic
and non-catatonic schizophrenia, major depressive
disorder (often with psychotic features) and medical
and neurological disorders.
• Because catatonia is a syndrome appearing in several
conditions, it does not imply a single diagnosis.
P. Ruiz.]
Postpartum Onset
• DSM-5 allows the specification of a postpartum

mood disturbance if the onset of symptoms is
within 4 weeks postpartum.
• Postpartum mental disorders commonly include
psychotic symptoms.
P. Ruiz.]
Seasonal Pattern
• Patients with a seasonal pattern to their mood disorders

tend to experience depressive episodes during a
particular season, most commonly winter.
• The pattern has become known as seasonal affective
disorder (SAD).
• The seasonal pattern may represent a separate diagnostic
entity especially that patients are likely to respond to
light therapy.
P. Ruiz.]
Depression: Clinical Features
• Depressed mood and a loss of interest or pleasure
are the key symptoms of depression.
• Patients may say that they feel blue, hopeless, in
the dumps, or worthless.
• For many patients, the depressed mood has a
different quality from the usual emotion of
sadness or grief. Patients often describe it as one
of agonizing emotional pain and sometimes
complain about being unable to cry.
P. Ruiz.]
• About two-thirds of patients contemplate suicide, and
10 to 15 % commit suicide.
• Those hospitalized for a suicide attempt or ideation
have a higher lifetime risk of completed suicide than
those never hospitalized for suicidal ideation.
• Some depressed patients may seem unaware of their
depression.
• Most depressed patients (97 %) complain of reduced
energy; difficulty finishing tasks; impaired functioning
at school and work; and decreased motivation to
undertake new projects.
P. Ruiz.]
• About 80% of patients complain of trouble sleeping,
especially early morning awakening (i.e., terminal
insomnia) and multiple awakenings at night during which
they ruminate about their problems.
• Many patients have decreased appetite and weight loss.
• Anxiety, a common symptom of depression, affects as
many as 90% of depressed patients.
• The changes in food intake and rest can aggravate
coexisting medical illnesses, such as diabetes,
hypertension, COPD, and heart disease.
• Other vegetative symptoms include decreased libido and
abnormal menses.
P. Ruiz.]
• Anxiety (including panic attacks), alcohol abuse and

somatic complaints (e.g., constipation, headaches) often
complicate the treatment of depression.
• 50% of patients describe a diurnal variation in their
symptoms, with increased severity in the morning and
lessening of symptoms by evening.
• Cognitive symptoms include inability to concentrate
(84%).
P. Ruiz.]
Children and Adolescents
• School phobia and excessive clinging to parents

may be symptoms of depression in children.
• Poor academic performance, substance abuse,
antisocial behavior, sexual promiscuity, truancy,
and running away from home may be symptoms
of depression in adolescents.
P. Ruiz.]
Geriatric Patients
• Depression is more common in the elderly than in the
general population (prevalence: 25%-50%).
• Depression in the elderly may correlate with low
socioeconomic status, loss of a spouse, physical
illness, and social isolation.
• Underdiagnosed and undertreated.
• The underrecognition of depression in the elderly may
occur because the disorder appears with somatic
complaints more often than in younger age groups.
• Ageism may also cause clinicians to accept
depressive symptoms as normal in older patients.
P. Ruiz.]
Depression: Epidemiology
• Lifetime prevalence: 5% - 17%
• Lifetime prevalence for women (10%–30%) is
double than that for men (7%–15%)
• The mean age of onset for depression is about 40
years. The incidence of depression may be
increasing among people younger than 20.
• More common in individuals without close
interpersonal relationships and those who are
divorced or separated.
• No correlation with socioeconomic status
• Suicide risk: 10%
P. Ruiz.]
Depression: Epidemiology
[Kaplan and Sadock's Comprehensive Textbook of Psychiatry (2009) by B. Sadock, V. Sadock

and P. Ruiz.]
Depression: Comorbidity
• Increased risk of having one or more comorbid
disorders. The most frequent comorbidities
(during a lifetime)1:
– alcohol use disorder (40%)
– generalized anxiety disorder (GAD) (15%)
– social anxiety disorder (13%)
– obsessive-compulsive disorder (OCD) (12%)
– panic disorder (10%)
• Comorbid disorders worsen the prognosis of
depressive illness and markedly increase the risk
of suicide.2
[1- Hasin DS, Goodwin RD, Stinson FS, Grant BF. Epidemiology of Major Depressive Disorder: Results From the
National Epidemiologic Survey on Alcoholism and Related Conditions. Arch Gen Psychiatry. 2005;62:1097-1106]
[2- Kaplan and Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry (2014) B. Sadock, V. Sadock
and P. Ruiz.]
Depression: Etiology
Biochemical Theories: Monoamine Hypothesis
• It was observed that certain medications had a

negative or positive effect on mood.
• Reserpine (depletes brain norepinephrine, serotonin,
and dopamine) made patients feel depressed, whereas
Iproniazid (inhibits the metabolism of norepinephrine,
serotonin, and dopamine) improved mood in patients
with tuberculosis.
• The resulting hypothesis was that depression is caused
by a deficit in monoamine neurotransmitters (and that
mania may result from the opposite).
[Kaplan and Sadock's Comprehensive Textbook of Psychiatry (2009) by B. Sadock, V. Sadock and P.
Ruiz.]
Monoamine Hypothesis:
All Antidepressant Classes Affect Monoamines
• Selective Serotonin Reuptake Inhibitors (SSRIs)
• Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)
• Tricyclic Antidepressants (TCAs)
• Monoamine Oxidase Inhibitors (MAOIs)
• Atypical Antidepressants
– Bupropion
– Mirtazapine
– Trazodone
– Nefazodone
– Vilazodone
– Vortioxetine
[Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications
(2013) by Stephen Stahl.]
Hypothalamic-Pituitary-Adrenal (HPA) Axis
Dysregulation
• Hypersecretion of cortisol over the 24-hour

circadian cycle has been observed in patients with
depression (especially psychotic depression).
• Studies have demonstrated a glucocorticoid-
mediated feedback impairment at the levels of the
pituitary and hypothalamus (de Kloet et al., 1998;
Young et al.,1991).
[Kaplan and Sadock's Comprehensive Textbook of Psychiatry (2009) by B.
Sadock, V. Sadock and P. Ruiz.]
Inflammation
• Recently, depression has been associated with pro-
inflammatory markers, including C-reactive protein
(CRP), interleukin-1, interleukin-6, and tumor
necrosis factor (TNF).
• These markers are present during significant stress
and can normalize with treatment of depression.
• Also, abnormalities in the inflammatory cascade may
mediate the relationship between depression and
medical illnesses (e.g., cancer).
[Kaplan and Sadock's Comprehensive Textbook of Psychiatry (2009) by B. Sadock, V.

Sadock and P. Ruiz.]
Brain-Derived Neurotrophic Factor (BDNF)
• A brain substance that promotes neuronal growth and
neuroplasticity in the developing brain.
• May play a role in the development and improvement of
depressive symptoms.
• Depression has indeed been associated with decreased size of
the amygdala, anterior cingulate, and prefrontal cortex.
• Decreased serum BDNF has been found in depressed patients.
• BDNF gene mutations have been associated with depression.
• ADs may increase level of BDNF.
[Kaplan and Sadock's Comprehensive Textbook of Psychiatry (2009) by B. Sadock, V.

Sadock and P. Ruiz.]
Integration of Hypotheses Regarding the Pathophysiology of Depression
• The brain of a depressed

individual has neurons with
fewer dendritic sprouts and
synapses.
• After recovery, neurons
exhibit increased dendritic
sprouts and synapses. The
chemical mediators of such
a transformation are
thought to include
monoamines, BDNF, and
CREB gene activation.
[Basic and Clinical Pharmacology, 12th ed.

(LANGE Basic Science, 2012) by B. Katzung,
S. Masters and A. Trevor.]
Structural and Functional Brain Imaging
• Computed tomography (CT) and magnetic resonance

imaging (MRI) are sensitive, noninvasive methods to
assess the brain.
• The most consistent finding in depressive disorder is
increased abnormal hyperintensities in subcortical
regions, such as the periventricular regions, basal
ganglia and thalamus.
• More common in bipolar I disorder and in the elderly,
these hyperintensities appear to reflect the
neurodegenerative effects of recurrent affective
episodes.
P. Ruiz.]
• Ventricular enlargement, cortical atrophy, and sulcal

widening also have been reported in some studies.
• Some depressed patients also have reduced
hippocampal or caudate nucleus volumes.
• Diffuse and focal areas of atrophy have been
associated with increased illness severity, bipolarity,
and increased cortisol levels.
• The most widely replicated positron emission
tomography (PET) finding in depression is decreased
anterior brain metabolism, which is generally more
pronounced on the left side.
P. Ruiz.]
[Simona Bonavita, Gioacchino Tedeschi, and Antonio Gallo, “Morphostructural MRI Abnormalities Related to
Neuropsychiatric Disorders Associated to Multiple Sclerosis,” Multiple Sclerosis International, vol. 2013, Article ID
102454, 6 pages, 2013]
Three-Dimensional Hippocampal Maps
- Statistical maps indicate local
differences in hippocampal structure
between MDD patients and controls,
in terms of percentage difference (B)
and statistical significance (C).
- Purple color indicates regions of
localized increase in size in MDD
patients vs. controls, whereas red
indicates relative thinning in MDD
patients vs. controls. Although overall
volumes did not differ, localized
increases (purple) were detected in
MDD patients in regions
corresponding to the CA1, subiculum
and presubiculum regions of the
hippocampus bilaterally.
[Altered hippocampal morphology in

unmedicated patients with major depressive
illness. Bearden CE et al. ASN Neuro.
2009; 1(4): e00020.]
Depression: Etiology 3-D statistical maps show
Structural and Functional Brain Imaging significant relationships between
Three-Dimensional Hippocampal Maps Hamilton Depression Rating Scale
score and regional hippocampal
atrophy within the depressed group
(left-hand depicts inferior view of
the hippocampus, right-hand
depicts superior view).
In the significance maps (bottom

panel), red and white colors denote
P values ≤0.05. Greater depression
severity was associated with greater
left hippocampal atrophy,
particularly in the subiculum and
CA1 regions of the hippocampus.
[Altered hippocampal morphology in

unmedicated patients with major depressive
illness. Bearden CE et al. ASN Neuro. 2009;
1(4): e00020.]
[http://www.mayoclinic.org/tests-
procedures/pet-scan/multimedia/-pet-scan-of-
the-brain-for-depression/img-20007400]
• Some studies observed reductions in cerebral blood

flow or metabolism, or both, in the dopaminergically
innervated tracts of the mesocortical and mesolimbic
systems in depression.
• Evidence suggests that antidepressants may partially
normalize these changes.
P. Ruiz.]
Neuroanatomical Considerations
• Four brain regions are important in the regulation

of emotions: the prefrontal cortex (PFC), the
anterior cingulate, the hippocampus, and the
amygdala.
• The PFC is implicated in planning complex
behaviors.
• The anterior cingulate cortex (ACC) is thought to
serve as the point of integration of attentional and
emotional inputs. Activation of the ACC
facilitates control of emotional arousal.
P. Ruiz.]
• The hippocampus is involved in various forms of
learning and memory, including fear conditioning
(a behavioral paradigm/model in which organisms
learn to predict aversive events), as well as
inhibitory regulation of the HPA axis activity.
• The amygdala appears to be a crucial way station
for processing novel stimuli of emotional
significance and coordinating or organizing
cortical responses.
P. Ruiz.]
P. Ruiz.]
Genetic Factors
• Numerous family, adoption and twin studies have
documented the heritability of mood disorders.
Recently, the primary focus of genetic studies has
been to identify specific genes using molecular
genetic methods.
• Twin studies provide the most powerful approach
to separating genetic from environmental factors
(“nature” vs. “nurture”). Twin data suggest that
genes explain 50 to 70 % of the etiology of mood
disorders.
P. Ruiz.]
Genetic Factors
• Gene-mapping studies of unipolar depression have found
evidence of linkage to the locus for cAMP response element
binding protein (CREB1) on chromosome 2.1
• Eighteen other genomic regions were found to be linked.1
• Another study suggested a role for gene-environment
interactions in developing depression
– Subjects who underwent adverse life events were at increased
risk for depression. Among them, those with a particular
variant in the serotonin transporter gene showed the greatest
increase in risk.2
– This is one of the first reports of a specific gene–environment
interaction in a psychiatric disorder. 2
[1- Kaplan and Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry (2014) B. Sadock, V. Sadock
and P. Ruiz.
2- Caspi A et al. Science. 2003;301:386-89].
Genetic Factors
• Research suggests a genetic link between stressful life
experiences and the onset of depression.
• In one study, subjects were assessed for stressful life
events occurring after their 21st and before their 26th
birthdays. Stressful events included employment,
financial, housing, health, and relationship stressors.
At age 26, patients were assessed for depressive
episodes during the prior year.
– Results: subjects carrying the “short” form of the serotonin
transporter gene were more likely to become depressed in
response to life stressors than subjects who were
homozygous for the “long” form of the gene.
– Among carriers of the “short” allele, the incidence of
depression increased relative to the number of life stressors
experienced. [Caspi A et al. Science. 2003; 301:386-89]
Genetic Factors: The 5-HT Transporter Gene and Stress-Induced
Depression
When exposed to 4 or more stressors, 33% of individuals who carry the “s”
allele (one or two copies) became depressed, while only 17% of individuals
who carry the “l/l” genotype did.
Occurrence of depression,
40
“Short” genotype “Long” genotype
(% of subjects†)
40
(n=581) (n=264)
20 20
n=184 n=138 n=104 n=64 n=91 n=79 n=73 n=57 n=26 n=29
0 0
0 1 2 3 4+ 0 1 2 3 4+
Number of stressful events* Number of stressful events*
* Genotype alone is not sufficient to predict onset of depression.

* Number of stressful life events:
– Significantly associated with occurrence of depression (p<0.001)
– Interacts significantly with genotype (p=0.05) to occurrence of
depression.
[Caspi A et al. Science. 2003; 301:386-89]
Depression: Etiology: The Cognitive Formulation
• According to the cognitive theory, depression results from

specific cognitive distortions present in persons susceptible
to depression.
• These distortions, referred to as schemata, are cognitive
templates that perceive both internal and external data in
ways that are altered by early experiences.
• Aaron Beck postulated a cognitive triad of depression that
consists of:
(1) views about the self—negative self-perception
(2) about the environment—tendency to experience the world as
hostile and demanding
(3) about the future—expectation of suffering and failure.
P. Ruiz.]
Depression: Case of Ms. C
• Ms. C, a 23-year-old woman, became acutely
depressed when she was accepted to a prestigious
graduate school.
• She had been working diligently toward this
acceptance for the past 4 years.
• She reported being “briefly happy, for about 20
minutes” when she learned the good news but
rapidly slipped into a hopeless state in which she
recurrently pondered the pointlessness of her
aspirations, cried constantly, and had to physically
stop herself from taking a lethal overdose of her
roommate’s insulin.
P. Ruiz.]
• In treatment, she focused on her older brother, who
had regularly insulted her throughout the course of her
life, and how “he’s not doing well.”
• She found herself very worried about him. She
mentioned that she was not used to being the
“successful” one of the two.
• In connection with her depression, it emerged that Ms.
C’s brother had had a severe, life-threatening, and
disfiguring pediatric illness that had required much
family time and attention throughout their childhood.
• Ms. C had become “used to” his insulting manner
toward her.
P. Ruiz.]
• In fact, it seemed that she required her brother’s abuse of her
in order not to feel overwhelmed by survivor guilt about being
the “healthy, normal” child.
• “He might insult me, but I look up to him. I adore him. Any
attention he pays to me is like a drug,” she said. Ms. C’s
acceptance to graduate school had challenged her defensive
and essential compensatory image of herself as being less
successful, or damaged, in comparison with her brother,
thereby overwhelming her with guilt.
• Her depression remitted in psychodynamic psychotherapy as
she better understood her identification with and fantasy
submission to her brother.
P. Ruiz.]
Depression: Case of Laura
• Laura came to therapy at the age of 42, having

experienced episodes of low mood and
depression since her early 20s.
• She had taken courses of antidepressants on
three previous occasions which had been helpful
• Her GP recommended that CBT might be
helpful to address underlying issues that might
be causing her chronic depression.
[http://www.uk-cbt.com/case-studies-laura.asp]
• Events in Laura’s life that emerged during
therapy included:
– a critical mother who often compared her to her sister
– a lifelong difficult relationship with her older sister
who was a high achiever
– moving to a different area of the country at the age of
10, resulting in the loss of her friends
– the loss of her grandfather when she was 14
– her parents’ disappointment when she did not earn
grades needed to get into university
• The goals Laura identified for therapy were:

– to be able to cope with everyday life without feeling
vulnerable and depressed all the time
– to have the confidence to go back to work now that
her children were old enough
– to be able to say “no” to friends and family who she
felt constantly expected too much of her
• During therapy, it became clear that Laura had
lifelong low self-esteem.
• No matter what she achieved (a good job, a
successful marriage, bringing up two children),
she felt she was never good enough.
• Laura was highly critical of herself, including
her attainments, her looks, and the fact that she
felt depressed for so many years.
• Examples of the techniques used in the therapy process:
– Compassionate Mind Training: a therapy-long process to
help Laura treat herself with the same kindness and
understanding that she showed those around her. Laura
realized that she was “human” and that meant not only
was she fallible, but also needed to feel cared for and
encouraged – as all people do
– Behavioral Homework: Laura had avoided social
activities for a long time and was sure she could not cope
with them again. In a gradual way, Laura increased her
social activities and learned from each experience that
she could cope, even when things were uncomfortable
• Laura had 23 one-hour sessions of CBT.
• The treatment was successful and she was able to start a
new job, increase her social activities, go on holiday,
and enjoy time with her family more than she had.
• One year after her therapy concluded, Laura felt she
was still gaining confidence, and handled a challenging
situation that occurred without feeling overwhelmed or
getting depressed.
Depression: Comorbid Disorders
• Medical conditions (other than depression) commonly
coexist with depression, especially in older persons.
• When depression and medical conditions coexist,
clinicians must try to determine whether the
underlying medical condition is pathophysiologically
related to the depression or whether any drugs that the
patient is taking for the medical condition are causing
the depression.
• Some studies indicate that treatment of a coexisting
depression can improve the underlying medical
disorder, including cardiac disease and cancer.
P. Ruiz.]
Depression: Coexisting Disorders: Cardiovascular Pathology
Depression: Mental Status Examination
• Psychomotor retardation is the most common MSE sign of
depression.
• A depressed patient may have stooped posture, decreased
spontaneous movements, and poor eye contact.
• 50 % of patients deny depressive feelings.
• Many depressed patients have decreased rate and volume of
speech and exhibit delayed responses to questions.
• Patients have negative views of the world and of themselves.
Their thought content often includes ruminations about loss,
guilt, suicide, and death.
• Patients commonly complain of impaired concentration and
forgetfulness.
• About two-thirds have suicidal ideation (10 to 15 % commit
suicide).
P. Ruiz.]
Depression: Illustration
P. Ruiz.]
Depression: Differential Diagnosis
• Mood disorder due to a general medical condition, e.g.,
adrenal dysfunction, hypo/hyper thyroidism,
mononucleosis, pneumonia (in elderly), cancer,
Parkinson’s disease, dementing illnesses.
• Medication-induced mood disorders, e.g., beta blockers,
antihypertensives, sedatives, analgesics, steroids, etc.
• Substance-induced mood disorder, e.g., alcohol, opiates,
stimulants, etc.
• Other psychiatric disorder, e.g., anxiety disorder,
schizophrenia, other mood disorder such as dysthymic
disorder (incomplete depressive syndrome without clear
episodes), bipolar disorder, etc.
• Whether a patient has unipolar or bipolar disorder can be a
challenging diagnostic question.
P. Ruiz.]
Depression: Differential Diagnosis
Features of Bipolar Depression
• Early age at onset
• Psychotic depression before 25 years of age
• Postpartum depression, especially one with psychotic features
• Rapid onset and offset of depressive episodes of short duration (<3 months)
• Recurrent depression (more than 5 episodes)
• Depression with marked psychomotor retardation
• Atypical features (reverse vegetative signs)
• Seasonality
• Bipolar family history
• High-density, three-generation pedigrees
• Trait mood lability (cyclothymia)
• Hyperthymic temperament (Hyperthymic is a word for “elevated mood.” Hyperthymic
individuals are usually lovers of life, cheerful, optimistic, confident, extraverted, and have high
energy levels.)
• Hypomania associated with antidepressants
• Repeated (at least 3 times) loss of efficacy of antidepressants after initial response
• Depressive mixed state (with psychomotor excitement, irritable hostility, racing thoughts, and
sexual arousal during major depression)
P. Ruiz.]
Depression: Course of the Disorder
• Onset: about 50% of patients having their first depression
exhibit significant depressive symptoms before the first
identified episode. The first depressive episode occurs
before age 40 years in about 50% of patients.
• Duration: an untreated episode lasts 6 to 13 months; most
treated episodes last about 3 months. Withdrawing
antidepressants before 3 months typically results in relapse.
• Development of mania: 5 to 10 % of patients with an initial
diagnosis of depression have a manic episode 6 to 10 years
after the first depressive episode.
P. Ruiz.]
Depression: Prognosis
• Major depressive disorder tends to be a
chronic, relapsing condition.
• Prognostic indicators:
– mild episodes, the absence of psychotic
symptoms, and a short hospital stay are good
prognostic indicators. Psychosocial indicators
of a good course include a history of solid
friendships during adolescence, stable family
functioning, and generally good social
functioning in the 5 years preceding the illness.
P. Ruiz.]
Depression: Treatment
• Treatments include pharmacotherapy,

psychotherapy, phototherapy, and
electroconvulsive therapy (ECT).
• Since stressful life events are associated with
increases in relapse rates, treatment should
also address stressors in patients’ lives.
P. Ruiz.]
Disorder
Condition
Disruptive Mood Dysregulation Disorder
(DMDD) : Case
P. Ruiz.]
(DMDD) : Case
P. Ruiz.]
(DMDD) : Case
P. Ruiz.]
Disruptive Mood Dysregulation Disorder (DMDD)
• A new addition to the DSM.
• Characterized by severe, developmentally
inappropriate, and recurrent temper outbursts at least
three times per week, along with a persistently
irritable or angry mood between temper outbursts.
• Symptoms must be present for at least a year, and the
onset must be by age 10.
• Studies suggest that youth with chronic irritability and
severe mood dysregulation are at higher risk for future
unipolar depressive disorders and anxiety disorders.
P. Ruiz.]
Disruptive Mood Dysregulation Disorder (DMDD) :
DSM-5 Diagnostic Criteria
Disruptive Mood Dysregulation Disorder (DMDD):
DSM-5 Diagnostic Criteria
Prevalence
• DMDD is common among children presenting to

mental health clinics.
• Prevalence estimates in the community are
unclear. Overall 1-year prevalence in children and
adolescents is probably 2%-5%.
• Rates are expected to be higher in males than in
females, and in children compared to adolescents.
Development and Course
• Rates of conversion to bipolar disorder are very

low.
• Children with chronic irritability are at risk to
develop unipolar depression and / or anxiety
disorders in adulthood.
Functional Consequences
• Marked disruption in a child’s family and peer

relationships, as well as in school performance.
• Because of their low frustration tolerance, such
children have difficulty succeeding in school and
sustaining friendships.
• Levels of dysfunction in children with bipolar
disorder and DMDD are generally comparable.
Also, dangerous behaviors and psychiatric
hospitalizations are common.
Comorbidity
• Rates of comorbidity in DMDD are very high.

• The strongest overlap occurs with oppositional
defiant disorder (ODD).
• Attention Deficit Hyperactivity Disorder (ADHD)
is also very frequently comorbid with DMDD.
• Children with DMDD present to clinical attention
with a wide range of disruptive behavior, mood,
anxiety, and even autism spectrum diagnoses.
Disorder
Condition
Persistent Depressive Disorder (Dysthymia)
• Its essential feature is a depressed mood that occurs for

most of the day, for more days than not, for at least 2
years (or at least 1 year for children and adolescents).
• Individuals whose symptoms meet major depressive
disorder criteria for 2 years should be given a diagnosis
of persistent depressive disorder (PDD) as well as
major depressive disorder (MDD).
• Because these symptoms have become part of the
individual’s day-to-day experience, they may not be
reported unless the individual is directly prompted.
Persistent Depressive Disorder (Dysthymia): DSM-5 Criteria
Persistent Depressive Disorder (Dysthymia):
Prevalence
• The 12-month prevalence in the US is

approximately 0.5% for PDD and 1.5% for
chronic MDD.
Development and Course
• PDD often has an early and insidious onset
and, by definition, a chronic course.
• Early onset (i.e., before age 21 years) is
associated with a higher likelihood of
comorbid personality disorders and
substance use disorders.
Comorbidity
• Compared to patients with MDD,

individuals with PDD are at a higher risk
for psychiatric comorbidity in general, and
for anxiety disorders and substance use
disorders in particular.
• Early-onset PDD is strongly associated with
Cluster B and C personality disorders.
Treatment
• Recent data offer the most objective support
for cognitive therapy, behavior therapy and
pharmacotherapy.
• The combination of pharmacotherapy and
some form of psychotherapy may be the
most effective treatment for the disorder.
P. Ruiz.]
Persistent Depressive Disorder (Dysthymia): Case
• A 27-year-old male grade-school teacher

presented with the chief complaint that life
was a painful duty that had always lacked
luster for him.
• He said that he felt “enveloped by a sense of
gloom” that was nearly always with him.
• Although he was respected by his peers, he
felt “like a grotesque failure, a self-concept
I have had since childhood.”
P. Ruiz.]
• He stated that he merely performed his

responsibilities as a teacher and that he had
never derived any pleasure from anything
he had done in life.
• He said that he had never had any romantic
feelings and that sexual activity with two
different women had involved pleasureless
orgasm.
P. Ruiz.]
• He said that he felt empty, going through

life without any sense of direction,
ambition, or passion, a realization that itself
was tormenting.
• He had bought a pistol to put an end to what
he called his “useless existence” but did not
attempt suicide, believing that it would hurt
his students and the small community in
which he lived.
P. Ruiz.]
Double Depression
• An estimated 40% of patients with major depressive
disorder also meet the criteria for dysthymia, a
combination often referred to as double depression.
• Double depression has a poorer prognosis than only
major depressive disorder.
• The treatment of patients with double depression
should target both disorders because the resolution of
the symptoms of major depressive episode still leaves
these patients with significant psychiatric impairment.
P. Ruiz.]
Disorder
Condition
Premenstrual Dysphoric Disorder
• Triggered by changing levels of sex hormones that
accompany the menstrual cycle.
• Occurs about 1 week before the onset of menses and is
characterized by irritability, emotional lability,
headache, anxiety, and depression.
• Somatic symptoms include edema, weight gain, breast
tenderness, syncope, and parasthesias.
• Approximately 5% of women are affected.
• Treatment is symptomatic and includes analgesics and
sedatives. Some patients respond to short courses of
SSRIs. Fluid retention is relieved with diuretics.
P. Ruiz.]
Premenstrual Dysphoric Disorder: DSM-5 Diagnostic Criteria
Premenstrual Dysphoric Disorder: DSM-5 Diagnostic Criteria
Premenstrual Dysphoric Disorder
• The generally recognized syndrome involves
– mood symptoms (e.g., lability, irritability)
– behavior symptoms (e.g., changes in eating patterns,
insomnia)
– and physical symptoms (e.g., breast tenderness,
edema, and headaches).
• These symptoms occur at a specific time during the
menstrual cycle, and resolve between menstrual cycles.
• The hormonal changes that occur during the menstrual
cycle are thought to cause the symptoms, although the
exact etiology is unknown.
P. Ruiz.]
Premenstrual Dysphoric Disorder:
Epidemiology
• The prevalence is unclear.
• Up to 80% of all women experience some
alteration in mood or sleep and some somatic
symptoms during the premenstrual period, and
about 40% of them have premenstrual symptoms
that prompt them to seek medical advice.
• Only 3 to 7% of women have symptoms that meet
the full diagnostic criteria for PMDD.
P. Ruiz.]
Premenstrual Dysphoric Disorder: Course and Prognosis
• Treatment includes support and recognition of the symptoms.

• SSRIs (e.g., fluoxetine) and benzodiazepine (e.g.,
alprazolam) have been reported to be effective.
• If symptoms are present throughout the menstrual cycle,
clinicians should consider one of the non-menstrual cycle-
related mood and anxiety disorders.
• The presence of especially severe symptoms should prompt
clinicians to consider other mood and anxiety disorders. A
thorough medical workup is necessary to rule out medical or
surgical conditions that may account for symptoms (e.g.,
endometriosis).
P. Ruiz.]
Disorder
Condition
Substance/Medication-Induced Depressive Disorder
• Depressed mood or markedly diminished interest or pleasure
in all, or almost all, activities
• There is evidence that
– The symptoms developed during or soon after substance
intoxication or withdrawal or after exposure to a medication
– The involved substance/medication is capable of producing
the symptoms.
• The symptoms are not better explained by a depression that is
not substance-induced.
• Lifetime-prevalence in the US: 0.26%
• Examples of culprit-agents: efavirenz, clonidine, isotretinoin,
corticosteroids, oral contraceptives, interferon.
Disorder
Condition
Depressive Disorder Due to Another Medical Condition
• Depressed mood or markedly diminished interest or pleasure
in all, or almost all, activities.
• There is evidence that the disturbance is the direct
pathopysiological consequence of another medical condition.
• The disturbance is not better explained by another mental
disorder (e.g., adjustment disorder in which the stressor is a
serious medical condition).
• There are clear associations with stroke, Huntington’s
disease, Parkinson’s disease, and traumatic brain injury.
• Several other conditions are associated with depression,
including Cushing’s disease, hypothyroidism and multiple
sclerosis.
Disorder
Condition
Other Specified Depressive Disorder
This category applies when symptoms of depression
predominate but do not meet the full criteria for any of
the disorders in the depressive disorders diagnostic class.
1. Recurrent brief depression: Concurrent presence of

depressed mood and at least 4 other symptoms of
depression for 2-13 days at least once per month for at least
12 consecutive months.
2. Short-duration depressive episode (4-13 days)
3. Depressive episode with insufficient symptoms:
Depressed affect and at least one of the other symptoms of
depression that persist for at least 2 weeks
Disorder
Condition
Unspecified Depressive Disorder
• This category applies to presentations in which
symptoms of depression predominate but do not
meet criteria for any of the disorders in the
depressive disorders diagnostic class.
• The unspecified category is used in situations in
which the clinician chooses not to specify the
reason that the criteria are not met for a specific
depressive disorder, and includes presentations for
which there is insufficient information to make a
more specific diagnosis (e.g., in emergency room
settings).
• Section II, Chapter 3: Bipolar and Related

Disorders.
• Section II, Chapter 4: Depressive
Disorders.
The DSM-5 Classification of Bipolar and Related
Disorders
• Bipolar I Disorder
• Bipolar II Disorder
• Cyclothymic Disorder
• Substance/Medication-Induced Bipolar and
Related Disorder
• Bipolar and Related Disorder Due to Another
Medical Condition
• Other Specified Bipolar and Related Disorder
• Unspecified Bipolar and Related Disorder
Famous Individuals with Bipolar Disorder:
Ernest Hemingway
• American novelist.
• 1954 Nobel prize winner in literature.
• Received electroconvulsive therapy
multiple times.
• Abused alcohol.
• Committed suicide in 1961 by
shooting himself.
• 4 relatives also died by suicide: father,
two siblings, granddaughter.
Famous Individuals with Bipolar Disorder:
Winston Churchill
• Prime minister of the UK during

the World War II.
• Referred to his recurrent
depression as his “black dog”.
• Used alcohol to ease mood and
anxiety symptoms.
• Had periods of extreme
productivity consistent with
mania.
DSM-5 Classification of Bipolar and Related Disorders
Related Disorder
Medical Condition
Bipolar I Disorder: Diagnosis
• The DSM-5 criteria for bipolar I disorder
– requires the presence of a distinct period of
abnormal mood lasting at least 1 week
– and includes separate bipolar I disorder
diagnoses for a single manic episode and a
recurrent episode based on the symptoms of the
most recent episode
* Manic episodes clearly precipitated by
antidepressant treatment (e.g., pharmacotherapy,
ECT) do not indicate bipolar I disorder.
P. Ruiz.]
• xx
DSM-5 Classification of Bipolar and Related Disorders
Related Disorder
Medical Condition
Bipolar II Disorder: Diagnosis
• The bipolar II disorder diagnosis requires
depressive and hypomanic episodes during the
course of the disorder. (The bipolar I disorder
diagnosis requires only a manic episode, with or
without depression episodes).
• Clinically, it may be difficult to distinguish
euthymia (normal mood) from hypomania in a
patient who has been chronically depressed for long
periods of time.
• As with bipolar I disorder, antidepressant-induced
hypomanic episodes are not diagnostic of bipolar II
disorder.
P. Ruiz.]
Bipolar Disorder: Rapid Cycling Specifier
• No data indicate that rapid cycling has a familial

pattern of inheritance; thus, external factors such as
stress or drug treatment may be involved in the
pathogenesis of rapid cycling.
• The DSM-5 criteria specify that the patient must
have at least four episodes within a 12-month period.
P. Ruiz.]
Bipolar and Related Disorders: Clinical Features
• The two basic symptom patterns in mood disorders are
depression and mania/hypomania.
• Depressive episodes can occur in both MDD and
bipolar I disorder.
• There are no reliable differences between bipolar I
disorder depressive episodes and episodes of major
depressive disorder. Only the patient’s history, family
history, and course can help differentiate the two
conditions.
• Some patients with bipolar I disorder have mixed
states with both manic and depressive features, and
some seem to experience brief—minutes to a few
hours—episodes of depression during manic episodes.
P. Ruiz.]
Bipolar and Related Disorders:
Clinical Features of Manic Episodes
• Elevated, expansive or irritable mood is the hallmark of
a manic episode.
• The elevated mood is euphoric and can even cause a
countertransferential denial of illness by an
inexperienced clinician.
• Although uninvolved persons may not recognize the
unusual nature of a patient’s mood, those who know the
patient well can recognize it as abnormal.
• Alternatively, the mood may be irritable, especially if a
patient’s unrealistic plan are thwarted.
• Patients often exhibit a change of predominant mood
from euphoria early in the course to irritability later.
P. Ruiz.]
• Gambling, casual sex, disrobing in public, wearing
bright clothing and jewelry in unusual or
outlandish combinations, and inattention can also
be symptoms of mania.
• Patients act impulsively and at the same time with
a sense of conviction and purpose.
• They are often preoccupied by religious, political,
financial, sexual, or persecutory ideas that can
evolve into complex delusional systems.
P. Ruiz.]
• Manic patients often drink alcohol excessively, perhaps
in an attempt to contain their energy or fall asleep.
Many use other substances as well.
• Treatment of manic patients in inpatient wards can be
complicated by their testing of the ward rules,
exploiting others’ perceived weaknesses, high-energy
and pacing, manifestations of euphoria (loud speech,
singing, dancing), and difficulty falling asleep.
P. Ruiz.]
Bipolar and Related Disorders: Epidemiology
• The annual incidence of bipolar illness (whether type 1 or
type 2) is less than 1%, but milder forms of bipolar
disorder are often missed.
P. Ruiz.]
[Kaplan and Sadock's Comprehensive Textbook of Psychiatry (2009) by B. Sadock, V. Sadock

and P. Ruiz.]
• Gender: Bipolar I disorder has an equal prevalence
among men and women. Manic episodes are more
common in men, and depressive episodes are more
common in women.
• Age: Onset of bipolar I disorder is earlier than MDD.
The age of onset for bipolar I disorder ranges from
childhood (as early as age 5) to 50 or older, with a mean
age of 30.
• Marital Status: Bipolar I disorder is more common in
divorced and single persons than among married
persons, but this may reflect the early onset and the
effects of the disorder.
P. Ruiz.]
Bipolar and Related Disorders: Comorbidity
• In both unipolar and bipolar disorder, men more

frequently present with substance use disorders,
and women with comorbid anxiety and eating
disorders.
• Comorbid substance use disorders and anxiety
disorders worsen the prognosis of the illness and
markedly increase the risk of suicide among
patients with a mood disorder.
P. Ruiz.]
Genetic Linkage Studies
• Chromosome 22q is a region thought to be
linked to bipolar 1 and bipolar 2 disorders.
• Chromosome 18q is thought to be linked to
bipolar 2 disorder.
• Several linkage studies have found evidence
for the involvement of specific genes in
clinical subtypes (e.g., 18q linkage has been
shown largely in bipolar II sibling pairs and
in families in which probands had panic
symptoms).
P. Ruiz.]
Bipolar and Related Disorders: Genetic Linkage Studies
• xx
P. Ruiz.]
Psychodynamic Factors in Mania
• In psychoanalytic theory, mania is seen as a

defense against underlying depression.
• In psychoanalytic theory, mania may also
result from a tyrannical superego, which
produces intolerable self-criticism that is
then replaced by euphoric self-satisfaction.
P. Ruiz.]
Bipolar and Related Disorders: Case of Ms. G
• Ms. G, a 42-year-old housewife and mother of a 4-
year-old boy, developed symptoms of hypomania and
later of frank mania without psychosis, when her only
son was diagnosed with acute lymphocytic leukemia.
• A very religious woman who had experienced 10
years of difficulty with conception, Ms. G was a
devoted mother. She reported that she was usually
rather down.
• Before her son’s illness, she used to joke that she had
become pregnant with him by divine intervention.
• During the first few weeks of his illness, doctors
regularly barraged Ms. G with bad news about his
prognosis
P. Ruiz.]
• Ms. G was ever present with her son at the hospital, never
sleeping, yet the pediatricians noted that as the child
became more debilitated and the prognosis more grim, she
seemed to bubble over with renewed cheerfulness, good
humor, and high spirits.
• She could not stop herself from cracking jokes to hospital
staff during her son’s painful procedures, and as the jokes
became more inappropriate, the staff grew more concerned.
• During her subsequent psychiatric consultation, Ms. G
reported that her current “happiness and optimism” were
justified by her “oneness” with Mary, the mother of God.
P. Ruiz.]
• “We are together now, she and I, and she

has become a part of me. We have a special
relationship,” she winked.
• Her mania later resolved when her son
achieved remission and was discharged
from the hospital.
P. Ruiz.]
Bipolar and Related Disorders (Bipolar 1 and 2):
Comorbid Disorders
• Substance use disorder, especially alcohol use disorder
• Anxiety disorder
• Personality disorder
• Attention Deficit Hyperactivity Disorder
P. Ruiz.]
Mental Status Examination
• Mood and Affect: manic patients classically present as
euphoric and/or irritable. They also have low
frustration tolerance, which can lead to expressions of
anger and hostility.
• Speech: loud, abundant, “pressured”. It often includes
jokes, play on words, and irrelevant detail.
• Thought form: thought associations can become loose.
Flight of ideas, clanging (word combinations based
upon sound rather than concepts), and neologisms
(new, invented words that are not readily
understandable) can also be present.
P. Ruiz.]
Mental Status Examination
• Thought content: delusions occur in 75 % of manic patients
and often involve wealth, extraordinary abilities
(“grandiosity”), special relationship with God, or sexual
themes.
• Sensorium and Cognition: orientation and memory are
intact, although some manic patients may be so euphoric that
they cannot focus on questions and answer incorrectly.
• Judgment: almost always impaired. Manic patients often
engage in high-risk activities, including impulsive sexual
activities, gambling, overspending, and inappropriate credit
card use and sometimes cause their families financial ruin.
• Insight: poor in the majority of cases.
P. Ruiz.]
Bipolar and Related Disorders
Mental Status Examination: Case of a 22-Year-Old Male
[http://www.jhasim.com/files/articlefiles/pdf/ASIM_Issue_4_10Dp904_907.pdf]
Mental Status Examination: Case of a 22-Year-Old Male
[http://www.jhasim.com/files/articlefiles/pdf/ASIM_Issue_4_10Dp904_907.pdf]
Differential Diagnosis
• The differential diagnosis for mania include: bipolar I
disorder, bipolar II disorder, cyclothymic disorder,
mood disorder caused by a general medical condition,
and substance-induced mood disorder. Psychotic
disorders also need to be ruled-out.
• Patients with borderline personality disorder often have
turbulent lives similar to patients with bipolar II
disorder, because of multiple episodes of disrupted
mood.
P. Ruiz.]
Course and Prognosis
• Bipolar disorder tends to be a chronic, relapsing
illness. The disorder negatively affects various
domains of patients’ lives.
• Course of bipolar I disorder: the disorder most
often starts with depression. Most patients
experience both depressive and manic episodes,
although 15% experience only manic episodes. An
untreated manic episode lasts about 3 months. As
the disorder progresses, the time between episodes
often decreases (“kindling”).
P. Ruiz.]
Course of Bipolar Type 1
• About 7% of patients with bipolar I disorder do not

have recurrence of symptoms.
• 45% have more than one episode.
• 40% have a chronic disorder.
P. Ruiz.]
Course and Prognosis: Life Chart of a Prototype-Case
P. Ruiz.]
Prognosis of Bipolar Type 1
• Poorer prognosis than MDD.
• Although lithium prophylaxis improves the course and
prognosis, only 60% of patients achieve significant control
of their symptoms with lithium.
• Poor prognostic factors include: premorbid poor
occupational status, alcohol dependence, psychotic features,
depressive features, inter-episode depressive features, and
male gender.
• Good prognostic factors include: short duration of manic
episodes, advanced age of onset, no suicidal thoughts, and
few psychiatric or medical comorbidities.
P. Ruiz.]
Course and Prognosis of Bipolar II Disorder
• Bipolar II disorder is a chronic disease that

warrants long-term treatment strategies.
P. Ruiz.]
Treatment
• Biological treatment options: pharmacotherapy and

electroconvulsive therapy (ECT). ECT is used for
cases of severe and resistant bipolar episodes
(especially when the risk of suicide is high).
• Psychotherapy (e.g., cognitive behavioral therapy) is
also very useful; however, it is frequently insufficient
by itself in severe bipolar disorder.
P. Ruiz.]
Treatment
• The pharmacological treatment of bipolar disorder is
divided into both acute and maintenance phases.
• Often, it is necessary to try different medications
before an optimal treatment is found.
• Available mood stabilizers include:
– Lithium (Li)
– Anticonvulsants (AC) : valproate, carbamazepine,
lamotrigine
– Atypical Antipsychotics (AA) : olanzapine,
quetiapine, risperidone, ziprasidone, clozapine,
aripiprazole
P. Ruiz.]
Principles in the Treatment of Bipolar Disorder
[Kaplan and Sadock's Synopsis

of Psychiatry: Behavioral
Sciences/Clinical Psychiatry
(2014) B. Sadock, V. Sadock
and P. Ruiz.]
Disorders
Related Disorder
Medical Condition
Cyclothymic Disorder
• Cyclothymic disorder is symptomatically a mild form

of bipolar II disorder, characterized by episodes of mild
hypomania and mild depression (bipolar II disorder is
characterized by major depressive and hypomanic
episodes).
• Lifetime prevalence of cyclothymia: about 1%
• Inclusion of cyclothymic disorder with the Bipolar and
Related Disorders implies a relation, probably
biological, to bipolar type I disorder. However, some
have postulated that it may be more related to
borderline personality disorder than to mood disorders.
P. Ruiz.]
Cyclothymic Disorder: DSM-5 Criteria
A. For at least 2 years (at least 1 year in children and adolescents) there have
been numerous periods of hypomanic symptoms that do not meet criteria for a
hypomanic episode and numerous periods of depressive symptoms that do not
meet criteria for a major depressive episode.
B. During the above period, the hypomanic and depressive periods have been
present for at least half the time and the individual has not been without the
symptoms for more than 2 months at a time.
C. Criteria for a major depressive, manic, or hypomanic episode have never
been met.
D. The symptoms in Criterion A are not better explained by a psychotic
disorder.
E. The symptoms are not attributable to the physiological effects of a
substance or another medical condition.
F. The symptoms cause clinically significant distress or impairment.
P. Ruiz.]
Bipolar and Related Disorders: Case of Mr. B
• Mr. B, a 25-year-old single man, came for an
evaluation due to irritability, insomnia, jumpiness,
and excessive energy.
• He reported that such episodes lasted from a few
days to a few weeks and alternated with longer
periods of feeling hopeless, dejected, and worn out
with thoughts of suicide.
• Mr. B reported having been this way for as long as
he could remember. He had never been treated for
his symptoms. He denied using drugs and said he
had “only the occasional drink to relax.”
P. Ruiz.]
Bipolar and Related Disorders: Case of Mr. B
• As a child, Mr. B went from one foster family to
another and was an irresponsible and trouble-
making child.
• He frequently ran away from home, was absent
from school, and committed minor crimes.
• He ran away from his last foster family at the age
of 16 years and drifted ever since, taking
occasional odd jobs.
• When he became restless at one location or job, he
quickly moved on to the next. He did not have
close friends because he would form and end
friendships quickly.
P. Ruiz.]
Disorders
Related Disorder
Medical Condition
Substance/Medication-Induced Bipolar and Related Disorder
• Elevated, expansive or irritable mood, with or without
depressed mood or markedly diminished interest or pleasure
in all, or almost all, activities
• There is evidence that
– The symptoms developed during or soon after substance
intoxication or withdrawal or after exposure to a
medication
– The involved substance/medication is capable of producing
the symptoms.
• The symptoms are not better explained by a bipolar or
related disorder that is not substance-induced.
• Lifetime-prevalence in the US: no studies available.
• Examples of culprit-agents: phencyclidine, stimulants,
steroids, interferons.
P. Ruiz.]
Disorders
Related Disorder
Medical Condition
Bipolar and Related Disorder Due to Another
Medical Condition
• A prominent and persistent period of abnormally
elevated, expansive or irritable mood and abnormally
increased activity or energy.
• There is evidence that the disturbance is the direct
pathophysiological consequence of another medical
condition.
• The disturbance is not better explained by another
mental disorder.
• Examples of medical conditions: Cushing’s disease,
multiple sclerosis, systemic lupus erythematosus,
stroke, etc.
P. Ruiz.]
Disorders
Related Disorder
Medical Condition
Other Specified Bipolar and Related Disorder
• This category applies when symptoms of bipolar and
related disorder predominate but do not meet the full
criteria for any of the disorders in the bipolar and related
disorders diagnostic class.
1. Short-duration hypomanic episodes (2-3days) and

major depressive episodes
2. Hypomanic episodes with insufficient symptoms and
major depressive episodes
3. Hypomanic episode without prior major depressive
episode
4. Short-duration cyclothymia (less than 24 months)
P. Ruiz.]
Disorders
Related Disorder
Medical Condition
Unspecified Bipolar and Related Disorder
• This category applies to presentations in which
symptoms of bipolar and related disorder
predominate but do not meet criteria for any of the
disorders in the bipolar and related disorders
diagnostic class.
• The unspecified category is used in situations in
which the clinician chooses not to specify the
reason that the criteria are not met for a specific
bipolar and related disorder, and includes
presentations for which there is insufficient
information to make a more specific diagnosis
(e.g., in emergency room settings).
P. Ruiz.]
References
• Kaplan and Sadock's Comprehensive Textbook of Psychiatry
(June 8, 2009) by B. Sadock, V. Sadock and P. Ruiz.
• Kaplan and Sadock's Synopsis of Psychiatry: Behavioral
Sciences/Clinical Psychiatry (August 26, 2014) B. Sadock, V.
Sadock and P. Ruiz.
• Stahl's Essential Psychopharmacology: Neuroscientific Basis
and Practical Applications (May 27, 2013) by Stephen Stahl.
• Prescriber's Guide: Stahl's Essential Psychopharmacology (May
15, 2014) by Stephen Stahl.
• Goodman and Gilman's The Pharmacological Basis of
Therapeutics, 12th ed. (January 10, 2011 ) by L. Brunton, B.
Chabner and B. Knollman.
• Basic and Clinical Pharmacology, 12th ed. (LANGE Basic
Science, January 3, 2012) by B. Katzung, S. Masters and A.
Trevor.

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Mood Disorders

Jean-Claude André Yazbek, MD

• Section II, Chapter 3 (pages 123-154):

• Section II, Chapter 3: Bipolar and Related

• When the world seems a dungeon, damp and small,

• When trawling rains have made their steel-grey fibres

• Suddenly bells are fiercely clanged about

• Then long processions without fifes or drums

• Fought depression with humor and

• Melancholia is one of the oldest terms in psychiatry, dating back to

• Presence of specific, predictable characteristics:

• The question of suicide disturbed him because it was

• DSM-5 allows the specification of a postpartum

• Patients with a seasonal pattern to their mood disorders

• Anxiety (including panic attacks), alcohol abuse and

• School phobia and excessive clinging to parents

[Kaplan and Sadock's Comprehensive Textbook of Psychiatry (2009) by B. Sadock, V. Sadock

• It was observed that certain medications had a

• Hypersecretion of cortisol over the 24-hour

[Kaplan and Sadock's Comprehensive Textbook of Psychiatry (2009) by B. Sadock, V.

[Kaplan and Sadock's Comprehensive Textbook of Psychiatry (2009) by B. Sadock, V.

• The brain of a depressed

[Basic and Clinical Pharmacology, 12th ed.

• Computed tomography (CT) and magnetic resonance

• Ventricular enlargement, cortical atrophy, and sulcal

[Altered hippocampal morphology in

In the significance maps (bottom

[Altered hippocampal morphology in

• Some studies observed reductions in cerebral blood

• Four brain regions are important in the regulation

* Genotype alone is not sufficient to predict onset of depression.

• According to the cognitive theory, depression results from

• Laura came to therapy at the age of 42, having

• The goals Laura identified for therapy were:

• Treatments include pharmacotherapy,

• DMDD is common among children presenting to

• Rates of conversion to bipolar disorder are very

• Marked disruption in a child’s family and peer

• Rates of comorbidity in DMDD are very high.

• Its essential feature is a depressed mood that occurs for

• The 12-month prevalence in the US is

• Compared to patients with MDD,

• A 27-year-old male grade-school teacher

• He stated that he merely performed his

• He said that he felt empty, going through

• Treatment includes support and recognition of the symptoms.

1. Recurrent brief depression: Concurrent presence of

• Section II, Chapter 3: Bipolar and Related

• Prime minister of the UK during

• No data indicate that rapid cycling has a familial

[Kaplan and Sadock's Comprehensive Textbook of Psychiatry (2009) by B. Sadock, V. Sadock

• In both unipolar and bipolar disorder, men more

• In psychoanalytic theory, mania is seen as a

• “We are together now, she and I, and she

• About 7% of patients with bipolar I disorder do not

• Bipolar II disorder is a chronic disease that

• Biological treatment options: pharmacotherapy and

[Kaplan and Sadock's Synopsis

• Cyclothymic disorder is symptomatically a mild form

1. Short-duration hypomanic episodes (2-3days) and

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