Journal of Child Psychology and Psychiatry 56:9 (2015), pp 949957 doi:10.1111/jcpp.

12426

Early identification of ADHD risk via infant

temperament and emotion regulation: a pilot study
Elinor L. Sullivan,1,2 Kathleen F. Holton,3 Elizabeth K. Nousen,4 Ashley N. Barling,1
Ceri A. Sullivan,4 Cathi B. Propper,5 and Joel T. Nigg4
1
Department of Biology, University of Portland, Portland, OR; 2Division of Diabetes, Obesity and Metabolism, Oregon
National Primate Research Center, Beaverton, OR; 3School of Education, Teaching & Health, Center for Behavioral
Neuroscience, American University, Washington, DC; 4Departments of Psychology and Behavioral Neuroscience,
Oregon Health and Science University, Portland, OR; 5Center for Developmental Science, University of North Carolina
at Chapel Hill, Chapel Hill, NC, USA

Background: Attention deficit hyperactivity disorder (ADHD) is theorized to have temperamental precursors early in
life. These are difficult to identify because many core features of ADHD, such as breakdowns in executive function
and self-control, involve psychological and neural systems that are too immature to reliably show dysfunction in
early life. ADHD also involves emotional dysregulation, and these temperamental features appear earlier as well.
Here, we report a first attempt to utilize indices of emotional regulation to identify ADHD-related liability in infancy.
Methods: Fifty women were recruited in the 2nd trimester of pregnancy, with overselection for high parental ADHD
symptoms. Measures of maternal body mass index, nutrition, substance use, stress, and mood were examined
during pregnancy as potential confounds. Offspring were evaluated at 6 months of age using LABTAB procedures
designed to elicit fear, anger, and regulatory behavior. Mothers completed the Infant Behavior Questionnaire about
their childs temperament. Results: After control for associated covariates, including maternal depression and
prenatal stress, family history of ADHD was associated with measures of anger/irritability, including infant negative
vocalizations during the arm restraint task (p = .004), and maternal ratings of infant distress to limitations
(p = .036). In the regulation domain, familial ADHD was associated with less parent-oriented attention seeking
during the still face procedure (p < .001), but this was not echoed in the maternal ratings of recovery from distress.
Conclusions: Affective response at 6 months of age may identify infants with familial history of ADHD, providing an
early indicator of ADHD liability. These preliminary results provide a foundation for further studies and will be
amplified by enlarging this cohort and following participants longitudinally to evaluate ADHD outcomes. Keywords:
ADHD risk, markers, early identification, maternal precursors, emotional dysregulation, infant temperament.

months and years after birth (Nigg, 2006b). These

Introduction
transactions would include early liability transmit-
Attention deficit hyperactivity disorder (ADHD) is
ted from the family as well as subsequent develop-
most commonly diagnosed in childhood but is the-
mental events. Thus, the purpose of examining early
orized to be rooted in early development, perhaps via
life markers is twofold: (a) to identify markers related
temperament (Nigg, 2006a); it is thus conceptualized
to familial liability and (b) to identify early indicators
as a neurodevelopmental disorder in DSM-5 (Amer-
of future disorder or disease.
ican Psychiatric Association, 2013). ADHD is unusu-
Identifying markers of ADHD liability before 2 or
ally heritable, with estimates well above 0.70 (Kan
3 years of age is difficult. Arnett, Macdonald, and
et al., 2013; Larsson, Chang, DOnofrio, & Lichten-
Pennington (2013) found correlations between Bay-
stein, 2013). As a result, the disorder is highly
ley scores and Child Behavior Check List behavior
familial, with substantially increased risk in off-
problems at age 15 months (girls) and 24 months
spring of parents with ADHD (Musser et al., 2014;
(boys) with ADHD symptoms in third grade (Arnett
Stawicki, Nigg, & von Eye, 2006), making parental
et al., 2013). However, they were unable to identify
ADHD an excellent proxy for offspring liability.
earlier predictors (and did not examine familial
Children with ADHD exhibit differences in brain
liability). Johnson, Gliga, Jones, and Charman
morphology by age five, which persist through ado-
(2015) reviewed the literature on correlations of
lescence (Castellanos et al., 2002) and reflect alter-
infant behavior and later ADHD (Johnson et al.,
ation in white matter development (Shaw et al.,
2015). They concluded that this literature remains
2006). This leaves open the possibility that the
sparse, although there is scattered evidence linking
developmental course of ADHD may begin very early
motor delays and isolated studies of attention but
in life, perhaps even in the perinatal period. We,
little convincing evidence of early infant markers in
along with others, have proposed that this disorder
the cognitive domain.
begins early in life and then unfolds through a series
Part of this challenge is because ADHD itself is
of developmental transactions in the ensuing
difficult to reliably characterize prior to 34 years of
age. Its behavioral symptoms (inattention, impulsiv-
Conflict of interest statement: No conflicts declared. ity, hyperactivity) are often normative in toddlers.

2015 Association for Child and Adolescent Mental Health.

Published by John Wiley & Sons Ltd, 9600 Garsington Road, Oxford OX4 2DQ, UK and 350 Main St, Malden, MA 02148, USA
950 Elinor L. Sullivan et al.
Furthermore, higher order cognitive abilities such as
executive functioning and reward discounting,
important in ADHD (Barkley, 1997), are not yet
sufficiently developed to markedly shape behavior
until the second or third year of life (Diamond, 2013).
Emotional systems, however, develop earlier and
are a promising early life target for ADHD liability. It
is increasingly recognized that ADHD is also
characterized by dysfunction in emotional systems
(Martel, 2009), in particular in negative emotionality
and irritability (Karalunas et al., 2014; Martel &
Nigg, 2006; Musser, Galloway-Long, Frick, & Nigg,
2013; Shaw, Stringaris, Nigg, & Leibenluft, 2014).
Theorists have argued that one developmental route
to ADHD involves early negative emotionality (Nigg,
Goldsmith, & Sachek, 2004; Sonuga-Barke, Auer-
bach, Campbell, Daley, & Thompson, 2005). Nega-
tive emotionality and its initial regulation (via dyadic
interchange with a parent as well as via orienting of
attention) can be reliably assessed in the first years
of life using well-established parental ratings and
observational measures (Buss et al., 2012; Calkins,
Dedmon, Gill, Lomax, & Johnson, 2002; Rothbart,
Sheese, Rueda, & Posner, 2011). Furthermore,
emerging evidence indicates that the evolution of
effortful control depends in part on the degree to
which negative emotionality is present in early life
(Posner, Rothbart, Sheese, & Voelker, 2014; Roth-
bart et al., 2011). Thus negative emotionality in the
first year may disrupt subsequent development of
effortful control and, by extension, could therefore
contribute as an early marker of risk for ADHD.
However, differentiation of the negative emotionality
domain is theoretically crucial. ADHD may be
related, at least in important subgroups of the
disorder, to alterations in positive as well as negative
emotionality, but anger/irritability emerges as the
principal aspect of negative emotionality in ADHD
(Karalunas et al., 2014; Shaw et al., 2014). More-
over, initial studies suggest that irritability in
infancy may predict later ADHD (Martel, Nikolas,
Jernigan, Friderici, & Nigg, 2012).
A family risk design is optimal for evaluating
liability markers in the early affective domain. This
approach was used to study ADHD in pioneering
studies by Auerbach and colleagues (Auerbach,
Atzaba-Poria, Berger, & Landau, 2004). They fol-
lowed 66 boys from birth and then divided them into
high and low risk groups based on high and low
levels of paternal symptoms of ADHD. At 7 months
of age, the paternal risk group showed higher levels
of anger (elicited by a LABTAB barrier task),
although this was not echoed in parent ratings of
anger [distress to limitations scale on the Infant
Behavior Questionnaire (IBQ-R) (Auerbach et al.,
2004)]. The same group noted parenting differences
at that age, suggesting that consideration of parent
characteristics in relation to child behaviors is
important (Landau, Amiel-Laviad, Berger, Atzaba-
Poria, & Auerbach, 2009).
J Child Psychol Psychiatr 2015; 56(9): 94957
The primary goal of this pilot study was to follow
up these effects and extend those findings by
including prenatal and postnatal evaluation. The
goal was to investigate differences in temperament
and emotional regulation of 6-month-old infants
with and without ADHD liability (defined by
parental history of ADHD) in order to evaluate
whether these traits serve as early life markers of
liability.
Methods
Participants
Recruitment. Women were recruited from a local univer-
sity-based prenatal care clinic at their 2nd trimester check-up
and were screened to over-represent family history of ADHD to
maximize eventual ADHD in the offspring. We enrolled 47
women through 50 pregnancies (three sibling pairs). Informed
consent was obtained at the time of enrollment, and all
procedures complied with federal guidelines and the local IRB.
Exclusions included high-risk pregnancy (morbid obesity,
pre-eclampsia), complicating life circumstances (homeless-
ness, underage status), active substance use (tobacco, mari-
juana, opioids), comorbid psychiatric conditions (bipolar
disorder, major depressive disorder), and psychiatric medica-
tion (Adderall, Wellbutrin, Prozac). Two children (one from a
sibling pair) were excluded after enrollment due to mothers
reporting substantial alcohol or drug use during early gesta-
tion of those pregnancies. This yielded a final N of 48 offspring
from 46 women.
Definition of familial ADHD risk. Each parents
genetic liability risk for offspring ADHD was coded. To do
this, parents reported whether they had ever been diagnosed or
treated for ADHD and rated their childhood and current
symptoms from the Barkley Adult ADHD Rating Scale (BAARS)
screener (Barkley, 2011). The BAARS provides national norms
and percentiles for ratings of childhood and current symptoms
and impairment. The algorithm for assigning a parent to the
risk group was as follows.
(1) Childhood: (a) Clear recollection of being diagnosed or
treated with stimulant medication for ADHD for a sustained
period or (b) childhood symptoms (recalled) exceeding 75th
percentile (BAARS Screen 7) and (2) Adulthood: BAARS rating
of 75th percentile or more (8). If no childhood ratings were
available (see below), the adulthood BAARS scores needed to
exceed the 80th percentile (BAARS screen 9).
At baseline, ratings were completed by both parents on
themselves in 13 of the families, by mother on both herself and
on the father in 10 families, and by mother on herself (with no
father data) in 25 families. To address these missing paternal
assessments, paternal self-ratings on the BAARS were
obtained at a postnatal behavioral visit. These were collected
in 20 of the 25 missing cases and used to finalize paternal and
thus familial status. In this way, the 48 motherinfant dyads
were grouped into 10 control pairs and 38 pairs with parental
ADHD. Of the 38 ADHD risk families, 8 were father only, 14
were mother only, 11 were both, and 5 were mother ADHD,
father unknown in which no reliable information on the
biological father was able to be obtained.
Measures
Parent ADHD symptoms. Current symptom scores
were computed using the BAARS-IV current symptom total
score for each parent. The highest score from either parent was
used as the dimensional ADHD family score.
2015 Association for Child and Adolescent Mental Health.
doi:10.1111/jcpp.12426
Parent ratings of child temperament. Temperament
was measured in two ways. First, mothers rated their infant on
the 191-item IBQ-R (Rothbart, 1981). Four scales were
selected a priori to target negative emotions, irritability, and
emotion regulation: (a) distress to limitations (anger), (b) fear,
(c) soothability, and (d) recovery from distress. In addition, a
negative emotion composite score was calculated by taking the
mean of distress to limitations, fear, sadness, and the inverse
of falling reactivity/rate of recovery from distress, as seen in
other studies assessing infant temperament (Clifford et al.,
2013). This composite was created primarily as a check on
parsimony, whereas our principal focus was on the distinction
between anger, fear, and ability to regulate (soothability and
recovery) as explained in the introduction.
Observations of child temperament: over-
view. Motherinfant dyads completed a behavioral assess-
ment when the infant was approximately 6 months old (average
age 6.7 months). The session lasted about 1.5 hr and was
videotaped for later coding. The testing room was equipped with
a high chair, a chair for the mother, and two cameras (one
focused on the infant, the other on the mother). At the start of the
visit, the mother and infant were given 3 min to acclimate to the
new environment without the tester present. Two specific
challenge paradigms were coded for the current report.
Still face paradigm. The well-established still face para-
digm (Moore & Calkins, 2004; Moore et al., 2009; Tronick, Als,
Adamson, Wise, & Brazelton, 1978) was used to measure the
infants reaction to the mothers lack of emotional response,
expected to elicit fear or sadness. This paradigm consisted of
the following 2-min episodes: normal face-to-face play inter-
action, still face interaction, and reunion play interaction. The
mother placed the infant in a high chair and sat in a chair
about an arms length away. During the normal play period,
the mother was instructed to play with the infant as she
normally would. The mother was then instructed to turn her
face away from the infant for 15 s and then turn back to face
the infant for the still face period, during which the mother
maintained a neutral and expressionless face and did not
interact with the infant. The mother was then instructed to
look away again for 15 s and then return to interacting and
playing with the infant as she normally would. If the infant
became persistently upset, the still face period was stopped
early, and the pair moved into the reunion period. Pacifiers and
other toys were not allowed during this task. Five infants data
were coded as missing because the mother interacted with the
infant during the still face period.
Arm restraint paradigm. The arm restraint task (Cal-
kins et al., 2002; Stifter & Braungart, 1995) immediately
followed the still face paradigm and was designed to measure
the infants response to a confining situation (distress to
limitations or anger/irritability). During this task, the mother
was instructed to avert her gaze and not interact with her child
while gently holding the infants arms to his or her sides for
1 min. The mother then released the infants arms and was
instructed to play and interact with her child normally for
2 min. If the infant became persistently distressed during arm
restraint, staff would direct the mother to move into the period
of normal play. Pacifiers and other comfort items were not
allowed during this task. Four infants data were coded as
missing because the mother interacted with the infant during
the arm restraint period.
Behavioral coding. Two observers blinded to familial
ADHD status coded each behavioral assessment video. Infants
behaviors were coded using a modified version of a published
coding scheme (Holochwost, Gariepy, Propper, Mills-Koonce, &
2015 Association for Child and Adolescent Mental Health.
Infant temperament as marker of ADHD liability 951
Moore, 2014; Moore et al., 2009). Infant behavior was coded
during the still face and arm restraint tasks in increments of 5-
s for four mutually exclusive behavioral categories: (a) affective
expression, (b) gaze, (c) vocalization, and (d) reactive/regula-
tory behavior. Affective expression was coded as Positive,
Negative, Obscure, or Neutral, and we recorded the percent of
the reaction that was negative for analysis. Vocalization was
coded as None/Not Negative or Negative; we retained the
percent negative for analysis. Reactive/regulatory behavior
was coded as Escape, Attention Seeking, Exploratory, or
Regulatory. We analyzed escape and attention seeking. Table 1
provides operational behavioral definitions. Infant behaviors
were coded through four separate viewings of the video: one for
each of the behavioral categories.
Reliability. Inter-observer reliability was determined by
analyzing percentage agreement and Cohens kappa (Cohen,
1960). All of the videos were assessed for agreement between
the two independent coders. The mean percentage agreement
between coders was 91.6% (range 87.4798.91) and the mean
Cohens kappa value was .74 (range .53.81).
Data reduction. The percentage of each episode that the
infants engaged in each behavior was determined by dividing
the total number of intervals when the infant engaged in each
behavior by the total number of intervals in that episode.
Behavior codings were averaged across two observers to create
final variables for analysis.
Confounds and covariates
Demographic information. Demographic information
(Table 2) was obtained at enrollment via maternal report.
Parent education was coded from 0 to 7 based on highest grade
completed for each parent. Maternal and paternal ages were
recorded at the time of enrollment. The birth date and sex of
the infant were obtained at sample collection on the day of
birth or through the medical records.
Maternal body mass index (BMI). Weight and height
were obtained from medical records and used to calculate
maternal BMI prior to pregnancy and during the second
trimester.
Maternal nutrition. Dietary data were collected using 24-
hr recalls conducted by research dietitians using the multipass
method. These 24-hr recalls were completed in the 2nd and
3rd trimester of pregnancy over 2 or 3 days, with one of the
days being a weekend day. The 24-hr recall data were used to
compute the Healthy Eating Index (HEI)-2010, as a measure of
overall maternal diet quality (Guenther et al., 2013). A higher
score indicates higher conformity to USDA recommendations.
Maternal substance use. Substance use was deter-
mined via self-report on the Achenbach Adult Self-Report (ASR)
questionnaire (Achenback & Rescorla, 2003) during the 2nd
and 3rd trimesters. The ASR includes questions that ask about
tobacco (number of times per day), alcohol (number of days the
respondent was drunk), and nonmedical drug (number of days
of use) usage during the past 6 months.
Parental stress. The Perceived Stress Scale (PSS) (Ezzati
et al., 2014) was used to obtain self-report of stress level
during the pregnancy. The average of 2nd and 3rd trimester
scores served as the outcome measure.
Maternal mood. Maternal depression was assessed with
the Center for Epidemiologic Studies Depression (CESD)
952 Elinor L. Sullivan et al. J Child Psychol Psychiatr 2015; 56(9): 94957

Table 1 Operational definitions for behavioral coding
Measure Behavior Description
Affective Positive Infants corners of mouth raised
expression and/or cheeks raised
Negative Infants brows may be sharply
lowered and eyes may be tightly
closed. This code includes anger,
sadness, and frustration
Obscure Infants mouth or face hidden
from view for the entire interval
Neutral Infant displaying a relaxed face
with no obvious muscle tension
Affective None/Not Infant is not vocalizing or
vocalization Negative vocalizations are not indicative of
being fussy or upset. This code
includes silence, cooing,
laughing, babbling, coughing,
and sneezing
Negative Infant is displaying negative
communication such as fussing,
crying, screaming (i.e. if upset or
angry), and other expressions of
mild fussiness
Reactive/ Escape Infant is attempting to get out of
regulatory the chair, often accompanied by
behavior negative vocalizations. Examples
include twisting, and struggling
back and forth
Attention Infant is trying to get the parents
seeking attention when the parent is not
engaging with the infant.
Examples include exaggerated
vocalizations or limbic movement
while the gaze is directed toward
the parent
(Roberts & Vernon, 1983) scale at the 2nd and 3rd trimester,
which were averaged to form one prenatal depressed mood
measure. The CESD was completed again by mothers at the
6 month time point.
Selection of covariates. Covariates were included in the
model if they were associated with family history of ADHD at
p < .20 in univariate analyses. These included maternal pre-
natal depression symptoms on the CESD (r = .27, p = .08),
maternal prenatal stress level from the PSS (r = .52, p < .01),
and maternal education (r = .32, p = .046). Current maternal
depression was also included as a covariate due to its obvious
importance as a potential explanation for infant negative
affect.
Data analysis
Statistical analyses were conducted using the MPLUS Editor
Version 7.3 (Muth
en & Muth
en, Los Angeles, CA). The effects of
family history were evaluated by computing zero order point-
biserial correlations with family history of ADHD. Significant
correlations were examined with linear regression with infant
behavior as the outcome and family ADHD group as the
predictor, with covariates as discussed above. Regression
coefficients were fully standardized and are reported with their
standard error of the mean (SEM), allowing estimation of a 95%
confidence interval, and traditional p-value. As noted earlier,
two sibling pairs were included; nonindependence was con-
trolled for using the MPLUS CLUSTER procedure. All p-value
tests are two-tailed. For correlations, we report both uncor-
rected p-values (due to the small sample size and preliminary
nature of the study) and Bonferroni-corrected p-values. Miss-
ing data varied across measures, but for all multivariate
models the covariance coverage matrix exceeded .50 at all
data points and so the data matrix easily fell within the
tolerance level of the maximum likelihood procedure (Enders,
2010). To maximize precision of the missing data matrix,
regressions were modeled using auxiliary variables from the
dataset (i.e. all variables reported in this paper served as
auxiliaries when not in the model), within the full information
maximum likelihood environment (Graham, 2003). This pro-
cedure uses all available data to estimate parameter values in
the presence of missing data (Enders, 2010). Auxiliary vari-
ables included in analysis were paternal education (maternal
education was a covariate); maternal and paternal age;
maternal and paternal ADHD (BAARS) scores; sex of child;
IBQ-R scales not in the dependent variable list (distress, fear,
falling reactivity/rate of recovery from distress and negative
emotion composite); maternal nutritional quality; mater-
nal prepregnancy BMI; and age of child at assessment.
For regressions, the two observational measures included in
Table 4 served as auxiliaries as well when not serving as the
dependent variable.

Table 2 Demographic characteristics of control and ADHD families

Control (n = 10) Familial ADHD (n = 38)

Mean (SD) Mean (SD) p-Value

Maternal age at birth (years) 30.9 (4.7) 30.7 (5.0) .926

Paternal age at birth (years) 33.6 (7.6) 33.7 (6.4) .966
Prenatal maternal BMI (kg/m2) 27.6 (4.4) 28.5 (7.0) .747
Gestational age at delivery (days) 281.6 (8.6) 277.3 (7.0) .158
Healthy Eating Index 61.5 (7.4) 63.0 (7.6) .616
Tobacco use during pregnancy (days) 0.0 (0) 0.3 (1.0) .454
Drunkenness during pregnancy (days) 0.0 (0) 0.1 (0.4) .314
Drug use during pregnancy (days) 0.0 (0) 0.0 (0)

Percent Percent p-Value

Infant male sex 50.0 63.2 .449

Divorced families 0.0 6.1 .449
Families with a single adult 22.2 18.2 .784
Maternal bachelors degree or higher 90.0 60.5 .079
Paternal bachelors degree or higher 75.0 63.6 .543

2015 Association for Child and Adolescent Mental Health.

doi:10.1111/jcpp.12426 Infant temperament as marker of ADHD liability 953

Results Regression models with all nominally significant

The zero order point-biserial correlations for all candi- measures, along with the covariates noted earlier,
date indicators of infant liability are listed in Table 3. were then evaluated. Those results are displayed in
Uncorrected p-values are reported along with p-values Table 4. Three of the indices remained significant
that are Bonferroni-corrected within the measurement after controlling for maternal prenatal and postnatal
domain (rating or observation) and a second value that mood, prenatal stress, and maternal education level;
is corrected across all 12 correlations in the table. Five IBQ-R fear effects were explained by the correlation
specific indicators had nominal associations of of ADHD liability with maternal stress during preg-
p < .05; three of these survived the local Bonferroni nancy, and IBQ negative affect was explained by
correction: IBQ-R distress to limitations, our proxy for maternal postnatal depressed mood. The combined
anger/irritability (higher in infants with familial results suggest that the most robust indicators of
ADHD), IBQ-R fear (higher in infants with familial early risk of ADHD are increased IBQ-R scores of
ADHD), and still face attention seeking, which was our distress to limitations and increased negative vocal-
indicator of adaptive coping or regulation (lower in izations during arm restraint; these converge con-
infants with familial ADHD). Figure 1A displays the ceptually (as indices of anger/irritability).
increase in negative vocalizations during arm restraint Two sets of secondary analyses were conducted.
in infants with familial history of ADHD, and Figure 1B First, we considered parental current ADHD symp-
displays the reduction in attention seeking during still toms alone for mother, father, and combined (high-
face in infants with a familial history of ADHD to est) in simple correlations following what is in
provide an illustration of the data. Table 3. Only one correlation was reliable (increased

Table 3 Correlations of family group with candidate infant liability markers of ADHD risk at age 6 months

Bonferroni-corrected p values

Behavioral measure r SE p Local Global (*12)

IBQ-R scales (corrected locally at p value *5)

IBQ-R distress to limits (anger) .592 .215 .006* .030* .072
IBQ-R fear .454 .137 .001* .005* .012*
IBQ-R soothability .067 .248 .787
IBQ-R rate of recovery to distress .025 .290 .932
IBQ-R negative affect composite .522 .229 .023* ns ns
Observational measures (corrected locally at p value *8)
AR negative affect .220 .212 .300
SF negative affect .035 .219 .870
AR negative vocalizations .443 .224 .048* ns ns
SF negative vocalizations .026 .221 .907
Attention seeking during AR .553 .581 .341
Attention seeking during SF .631 .149 <.001* <.008* <.012*
Escape behavior during AR .179 .225 .426
Escape behavior during SF .014 .195 .941

IBQ-R, Infant Behavior Questionnaire; AR, arm restraint task; SF, still face paradigm.
Correlations were derived by computing individual point-biserial correlations one by one, in separate models. Each model included
the list of auxiliary variables: maternal and paternal age, education, and current ADHD score on the BAARS-IV, age of child at
assessment, sex of child, maternal BMI, maternal nutrition, and all IBQ-R and behavior variables shown in the table. Auxiliary
variables are not covariates. Bonferroni correction within this table was conducted in two ways: locally within measurement type,
and globally across all measures in the table.

(A) Negative vocalizations during (B) Attention seeking behavior

arm restraint during still face
Percentage of observation
Percentage of observation

80 40

*
60 30

40 20

20 10 *

0 0
Control Familial ADHD Control Familial ADHD
ADHD Status ADHD Status

Figure 1 Infants with a familial history of ADHD show increased negative vocalizations during the arm restraint paradigm (p = .004) (A),
as well as decreased attention-seeking behavior during the still face paradigm (p < .001) (B). Data are presented as the mean  SEM.

2015 Association for Child and Adolescent Mental Health.

954 Elinor L. Sullivan et al. J Child Psychol Psychiatr 2015; 56(9): 94957

Table 4 Regression modeling of the association of infant

emotion/irritability behavioral markers with ADHD familial Discussion
history after controlling for covariates Identification of early precursors for ADHD is of
central importance because early intervention could
Coefficient SE p-Value be more successful than interventions after estab-
Outcome 1: IBQ-R distress to limitations (irritability/anger) lishment of ADHD. The present study examined a set
Family risk group .378 .180 .036* of conceptually relevant emotional temperament indi-
Maternal education .344 .164 .036* cators in 6-month-old infants with a parental history
Prenatal stress .211 .272 .438
of ADHD. These results should be understood as
Prenatal depression .182 .363 .616
Postnatal depression .499 .230 .030* preliminary due to the small nature of the sample and
Outcome 2: IBQ-R fear in particular the small control sample, which limits
Family risk group .261 .180 .146 power and increases the risk of nonreproducibility.
Maternal education .119 .149 .425 With that important caution, intriguing findings
Prenatal stress .945 .361 .009*
emerged that may guide further work in this area.
Prenatal depression .875 .453 .053
Postnatal depression .302 .239 .206 Laboratory observation and parental rating were
Outcome 3: IBQ-R negative affect composite used to examine measures of negative affectivity and
Family risk group .266 .194 .170 its components of anger/distress versus fear (in
Maternal education .157 .175 .371 hopes of capturing affect related to irritability as it
Prenatal stress .072 .472 .878
appears later in ADHD), as well as early indices of
Prenatal depression .286 .518 .581
Postnatal depression .590 .270 .029* emotional self-regulation in the form of attention
Outcome 4: Negative vocalizations during AR (irritability/ seeking and escape behaviors during two challenge
anger) tasks. The most robust results were replicated across
Family risk group .452 .158 .004* ratings and observations, and were not accounted for
Maternal education .345 .179 .054
by key covariates including maternal prenatal stress
Prenatal stress .426 .353 .228
Prenatal depression .213 .431 .621 and prenatal and concurrent depressed mood.
Postnatal depression .688 .287 .017* The most notable result appears to be in the domain
Outcome 5: Attention seeking during SF (positive coping/ of infant anger/irritability indicated by higher mater-
regulation) nal ratings on the distress to limitations scale of the
Family risk group .562 .142 <.001*
IBQ-R and the laboratory observation of negative
Maternal education .177 .142 .213
Prenatal stress .401 .257 .118 vocalizations during arm restraint. These measures
Prenatal depression .505 .258 .050 are conceptually similar to the clinical construct of
Postnatal depression .133 .137 .333 irritability in older children which is defined by the
Research Domain Criteria as a metric of frustration to
Family risk group 1 = control, 2 = risk, so a positive coefficient
nonreward (Leibenluft & Stoddard, 2013). This find-
means more of the behavior in the risk group. Prenatal stress is
maternal rating on the Perceived Stress Scale averaged across ing also converges with a key finding from Auerbach
2nd and 3rd trimester. Prenatal depression is maternal C-ESD and colleagues (Auerbach et al., 2004).
rating averaged across 2nd and 3rd trimester. Postnatal Infants with a familial history of risk for ADHD also
depression is maternal CESD score at the 6 month infant exhibited reduced self-regulation strategies. One
follow up visit. Auxiliary variables were maternal and paternal
indicator was a reduction in attention-seeking
age, current ADHD score on the BAARS-IV, and paternal
education (maternal education is in the model), age of child at behavior toward their mothers during the still face
assessment, sex of child, maternal BMI, maternal nutrition, paradigm. A decrease in parent-orienting behavior
and all IBQ-R and behavior variables in this table that were not during the still face paradigm was previously asso-
in the particular model. Auxiliary variables are not covariates ciated with infant negative affect (Braungart-Rieker,
but reduce the error term by improving precision of the missing
Garwood, Powers, & Notaro, 1998). Also, consistent
data matrix.
with our findings, boys with ADHD show impair-
maternal ADHD symptoms was associated with ments in recognizing and responding to facial emo-
decreased infant escape behaviors during still face; tions (Yuill & Lyon, 2007). Deficits in self-regulation
full results available on request), suggesting in are a common feature in a substantial number of
general limited effect of parental current symptoms children with ADHD, and the behavior seen here may
compared to parental lifetime ADHD status. be an early indicator in that domain (Anastopoulos
Second, we examined the effects of paternal versus et al., 2011; Martel, 2009).
maternal ADHD status separately (based on lifetime Effects for regulatory strategies, however, were not
group assignment). These effects (available on echoed in maternal report of infant behavior in the
request from the authors) were generally weak. Only IBQ-R. Maternal ratings are dependent on the childs
maternal diagnosis with lower escape behaviors home environment, which is likely to be influenced by
during still face survived Bonferroni correction; no parental ADHD diagnosis. In contrast, the testing
effects survived covariate control. This suggested procedure and environment is highly controlled in
that familial transmission was not accounted for by laboratory observations of infant temperament,
one parent but rather was emanating to some extent which may explain why differences in self-regulatory
from both parents. strategies were not detected in maternal report.

2015 Association for Child and Adolescent Mental Health.

doi:10.1111/jcpp.12426
Although study groups were relatively well matched
on most demographic variables, familial history of
ADHD was associated with prenatal exposure to
higher maternal stress and depression and marginally
lower maternal education. Elevated prenatal stress
has been documented to disrupt emotional regulation
and impair offspring cognition (Buss et al., 2012;
Sandman, Davis, Buss, & Glynn, 2012), so controlling
for this measure was extremely important. Interest-
ingly, maternal report of stress during gestation was
associated with increased infant fear, consistent with
previous findings (Davis, Glynn, Waffarn, & Sand-
man, 2011; Sandman et al., 2012). It is important that
future studies of infant behavior include additional
measures of maternal stress responsivity and further
examine the influence of maternal stress on infant
behavior. We did not examine other maternal behav-
iors, attachment, or overall parentchild relationship
quality. These will be important to consider in further
work as mediators and moderators of the effects seen.
The assessment of ADHD in the parents was
limited by reliance on maternal ratings of father for
several cases, by absence of informants who knew
the parents when they were children, and by absence
of a structured clinical interview of parents. Thus,
these are families with high suspicion but not
definitive ADHD. Likewise, an important caution is
that we studied ADHD liability; only some of these
children will later develop ADHD. Indeed, work of
this nature in other disorders, such as autism, has
identified apparent liability markers in infancy that
fail to predict later disorder (Jones, Gliga, Bedford,
Charman, & Johnson, 2014). Therefore, it is impor-
tant to reserve judgment on the meaning of these
infant findings until we are able to evaluate children
at 3 and 4 years of age or older to determine the
forward predictive utility of infant biomarkers in
predicting emerging ADHD diagnosis.
Attention deficit hyperactivity disorder is familial
and heritable (Stawicki et al., 2006). Evidence from
twin studies estimate heritability of about 70% (Burt,
2009; Faraone et al., 2005). ADHD risk can be
transmitted from parents to offspring via three
fundamental mechanisms: genetics, shared environ-
ment, and developmental programming via epige-
netic modifications. It is plausible that parents
transmit liability or susceptibility to ADHD, which
is then presumably activated by early experiences
Key Points
Seeks to identify indicators of ADHD family liability at age 6 months that may predict later ADHD risk.
Parental history of probable ADHD was associated with both rated and observed distress to limitations in
infants, suggesting that an irritability-like phenotype is a marker of ADHD liability.
We provide preliminary evidence that differences in emotional regulation are detectable in infancy and may
be important biomarkers for early identification of ADHD.
2015 Association for Child and Adolescent Mental Health.
Infant temperament as marker of ADHD liability 955
(Nigg, 2006a, 2006b). Familial transmission is likely
a complex interaction between environmental,
genetic, and epigenetic factors that contribute to
the heterogeneity in ADHD symptomatology (Archer,
Oscar-Berman, & Blum, 2011).
In the current study, differences between infants
with and without family history of ADHD remained
after covariates such as maternal stress and mood
were controlled, suggesting a genetic transmission of
liability. Further, the familial status based on lifetime
parent assignment (including parental child and
adult symptom reports) provided robust prediction
of infant temperament, whereas current parental
symptoms did not. This also suggests transmission
of genetic liability rather than shared environment.
However, the present study lacked power to examine
interactions between family risk and early experience,
such as prenatal maternal stress, nutrition or early
caregiving. These types of interactions are very likely
to be important for individual differences in outcome
and need to be examined in a larger population to
clarify developmental processes of transmission. The
study also lacked power to consider sex-specific
transmission (e.g. from fathers to sons, as studied
by Auerbach et al., 2004); this will be another inter-
esting future target.
In conclusion, these findings, while preliminary,
provide promising suggestion that measures of neg-
ative emotionality, particularly those related to irri-
tability and its regulation, may provide promising
indices for early detection of ADHD. Continuing to
follow these infants while increasing the sample size
is a logical next step to evaluate this proposal further.
Acknowledgements
This original article was invited by the journal as part of
a special issue; it has undergone full, external peer
review. This work was supported by the Abracadabra
Foundation. The authors have declared that they have
no competing or potential conflicts of interest in relation
to the work reported.
Correspondence
Joel T. Nigg, Oregon Health and Science University,
3550 SW US Veterans Hospital Road, Mail Code: DC7P,
Portland, OR 97239, USA; Email: niggj@ohsu.edu
956 Elinor L. Sullivan et al.
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Accepted for publication: 13 April 2015
Published online: 12 May 2015