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Disruptions of working memory and inhibition mediate the association between exposure to institutionalization and symptoms of attention deficit hyperactivity disorder


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Background: Young children raised in institutions are exposed to extreme psychosocial deprivation that is associated with elevated risk for psychopathology and other adverse developmental outcomes. The prevalence of attention deficit hyperactivity disorder (ADHD) is particularly high in previously institutionalized children, yet the mechanisms underlying this association are poorly understood. We investigated whether deficits in executive functioning (EF) explain the link between institutionalization and ADHD. Method: A sample of 136 children (aged 6-30 months) was recruited from institutions in Bucharest, Romania, and 72 never institutionalized community children matched for age and gender were recruited through general practitioners' offices. At 8 years of age, children's performance on a number of EF components (working memory, response inhibition and planning) was evaluated. Teachers completed the Health and Behavior Questionnaire, which assesses two core features of ADHD, inattention and impulsivity. Results: Children with history of institutionalization had higher inattention and impulsivity than community controls, and exhibited worse performance on working memory, response inhibition and planning tasks. Lower performances on working memory and response inhibition, but not planning, partially mediated the association between early institutionalization and inattention and impulsivity symptom scales at age 8 years. Conclusions: Institutionalization was associated with decreased EF performance and increased ADHD symptoms. Deficits in working memory and response inhibition were specific mechanisms leading to ADHD in previously institutionalized children. These findings suggest that interventions that foster the development of EF might reduce risk for psychiatric problems in children exposed to early deprivation.
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Disruptions of working memory and inhibition
mediate the association between exposure to
institutionalization and symptoms of attention decit
hyperactivity disorder
F. Tibu
*, M. A. Sheridan
, K. A. McLaughlin
, C. A. Nelson
, N. A. Fox
and C. H. Zeanah
Institute of Child Development, Bucharest, Romania
University of North Carolina, Chapel Hill, USA
University of Washington, Seattle, USA
Harvard University, Boston, USA
Boston Childrens Hospital, Boston, USA
University of Maryland, College Park, USA
Tulane University, New Orleans, USA
Background. Young children raised in institutions are exposed to extreme psychosocial deprivation that is associated
with elevated risk for psychopathology and other adverse developmental outcomes. The prevalence of attention
decit hyperactivity disorder (ADHD) is particularly high in previously institutionalized children, yet the mechanisms
underlying this association are poorly understood. We investigated whether decits in executive functioning (EF) explain
the link between institutionalization and ADHD.
Method. A sample of 136 children (aged 630 months) was recruited from institutions in Bucharest, Romania, and 72
never institutionalized community children matched for age and gender were recruited through general practitioners
ofces. At 8 years of age, childrens performance on a number of EF components (working memory, response inhibition
and planning) was evaluated. Teachers completed the Health and Behavior Questionnaire, which assesses two core fea-
tures of ADHD, inattention and impulsivity.
Results. Children with history of institutionalization had higher inattention and impulsivity than community controls,
and exhibited worse performance on working memory, response inhibition and planning tasks. Lower performances on
working memory and response inhibition, but not planning, partially mediated the association between early institution-
alization and inattention and impulsivity symptom scales at age 8 years.
Conclusions. Institutionalization was associated with decreased EF performance and increased ADHD symptoms.
Decits in working memory and response inhibition were specic mechanisms leading to ADHD in previously institu-
tionalized children. These ndings suggest that interventions that foster the development of EF might reduce risk for
psychiatric problems in children exposed to early deprivation.
Received 24 November 2014; Revised 4 September 2015; Accepted 7 September 2015
Key words: ADHD, children, early deprivation, executive functioning.
Institutionalization is a widespread phenomenon in
low- and middle-income countries (UNICEF, 2010)
that puts young children at risk for adverse develop-
ment and health outcomes. The deleterious effects of
institutionalization are evident in numerous develop-
mental domains, both physical and psychosocial, and
can be long-lasting (Rutter et al. 2010). Young children
raised in institutions exhibit profound decits in cogni-
tive, emotional and social functioning (Rutter et al.
2010; Nelson et al. 2014). Elevations in psychopath-
ology are particularly marked in previously insti-
tutionalized children (Rutter et al. 2001; Zeanah et al.
2009; Humphreys et al. 2015).
The Bucharest Early Intervention Project (BEIP) was
designed to examine the effects of a foster care inter-
vention among institutionalized children on subse-
quent brain and behavioral development (Zeanah
et al. 2003; Nelson et al. 2014). In this study, exposure
to institutionalization was associated with elevations
in both internalizing and externalizing disorders, but
only internalizing disorders were remediated through
* Address for correspondence: F. Tibu, Ph.D., Institute of Child
Development, 17 Maresal Averescu Blvd. Complexul de Servicii
Sociale Sfanta Ecaterina, Corp C, Etaj 1, Bucharest 011454, Romania.
Psychological Medicine, Page 1 of 13. © Cambridge University Press 2015
doi:10.1017/S0033291715002020 ORIGINAL ARTICLE
placement into foster care at 4½ years (Zeanah et al.
2009). By contrast, exposure to institutionalization
was associated with an increased risk for externalizing
disorders that was not improved by placement into
foster care. Twenty-one percent of children raised in
institutions met criteria for attention decit hyperactiv-
ity disorder (ADHD) by age 4½ years, even if they later
lived in a foster care family (Zeanah et al. 2009); at 12
years the rate of ADHD was 19.3% (Humphreys et al.
2015). High rates of ADHD have also been observed
in other studies of children reared in institutions
(Kreppner et al. 2001; Stevens et al. 2008) and they are
markedly higher than in never institutionalized chil-
dren, where the prevalence of ADHD is estimated to
be between 3% and 10% (Kessler et al. 2006; Spencer
et al. 2007). Indeed, symptoms of ADHD are so com-
mon among previously institutionalized children,
that some have argued that they represent one type
of deprivation-specic behavior patterns (Kreppner
et al. 2001; Rutter et al. 2010). Yet the mechanisms
that mediate the link between institutionalization and
elevated risk for ADHD are poorly understood.
Executive Functioning (EF) decits are strongly asso-
ciated with ADHD symptoms (Barkley, 1997; Sergeant,
2000; Martinussen et al. 2005; Willcutt et al. 2005;
Schoemaker et al. 2012). However, EF and ADHD are
not synonymous and current research has emphasized
the heterogeneity in cognitive function observed in the
population of children diagnosed with ADHD (Fair
et al. 2012). It has been widely hypothesized that this
heterogeneity reects as yet unidentied subpopula-
tions of children with ADHD currently subsumed
under the umbrella diagnosis (Willcutt et al. 2005;
Halperin & Schulz, 2006), and it is possible that
ADHD following exposure to childhood adversity is
one of these subpopulations. In this case, we would ex-
pect that children with ADHD following institutional-
ization would not necessarily evidence the same EF
decits often observed in other populations of children
with ADHD. EF generally refers to a set of higher-
order functions that regulate cognition and behavior
and can be broken into three to four interrelated yet
distinct domains: inhibition, working memory, set-
shifting and planning (Sonuga-Barke et al. 2002;
Niendam et al. 2012). Institutionalization is also asso-
ciated with decits in multiple aspects of EF, in pre-
school and school-aged children, including working
memory, set-shifting, and inhibitory control (Colvert
et al. 2008; Bos et al. 2009; Pollak et al. 2010; Hostinar
et al. 2012; Loman et al. 2013; McDermott et al. 2013;
Merz et al. 2013). Similar to the pattern observed in
ADHD, EF improvements have not been observed fol-
lowing early intervention (Bos et al. 2009). It is possible
that the risk for ADHD conferred by institutionaliza-
tion is explained by the effect of early institutional
rearing on EF. We explore this hypothesis in the cur-
rent report.
The possibility of an early neurodevelopmental
mechanism linking environmental experience to
ADHD (Taylor & Rogers, 2005; Stevens et al. 2008)is
suggested by studies linking other types of early ad-
verse environments other than institutionalization to
ADHD (Biederman et al. 1995; McLaughlin et al.
2010b). Decits in EF have also been observed in chil-
dren exposed to various adverse conditions, such as
maltreatment (Pears et al. 2010) and witnessing domes-
tic violence (DePrince et al. 2009). Few studies have
examined the underlying factors leading to psycho-
pathology in previously institutionalized children.
Those studies that have been conducted found links
between atypical brain functioning and ADHD
(McLaughlin et al. 2010a, 2014; Slopen et al. 2012). To
our knowledge, there is only one previous study (i.e.
Colvert et al. 2008) that explored the possible mediating
role of EF in the link between institutionalization and
psychopathology. However, this study is limited by a
single task assessing inhibitory control. In the current
study we extend this previous report by examining
the role of EF as a mechanism linking institutionaliza-
tion to ADHD symptoms using a more comprehensive
assessment of EF.
The current investigation presents data from the
BEIP sample at 8 years of age. Previous reports on
these data showed that the children with history of in-
stitutional rearing had increased inattention and im-
pulsivity symptoms (McLaughlin et al. 2014) and
decreased performance on working memory (Bos
et al. 2009) and inhibition (McDermott et al. 2013).
Here, we expected to nd links between the childrens
EF abilities and their ADHD symptoms. Furthermore,
we predicted that elevations in ADHD symptoms in
the institutionalized children would be mediated by
differences in EF abilities.
Participants were children from the BEIP, a longitu-
dinal study of the effects of institutionalization and
the only randomized controlled trial of foster care for
children raised in institutional settings (Zeanah et al.
2003; Nelson et al. 2014). A total of 136 children living
in institutions in Bucharest, Romania were recruited
during infancy (age range 631 months, mean age =
22 months). Following recruitment and baseline testing
the children were randomly assigned to a care as
usual group (CAUG, N= 68) or a foster care group
(FCG, N= 68). Children in the CAUG received care as
usual, meaning that they remained in institutional
2F. Tibu et al.
care longer, and children in the FCG were placed in a
network of foster families selected and trained by
study investigators living in Bucharest. Seventy-two
never institutionalized (NIG) children raised by their
families in the community also were recruited to
serve as controls. Details on study design and partici-
pants have been described previously (see Zeanah
et al. 2003). Study procedures were approved by the
local commissions on child protection in Bucharest
and approved by an ethics committee comprising
appointees from government and Bucharest University
academic departments. The study was approved and
overseen by the institutional review boards of the
home institutions of the three principal investigators.
A complete description of procedures employed to en-
sure ethical integrity has been published previously
(Zeanah et al. 2012).
The current study presents data from the sample of
children who completed neuropsychological testing
at a follow-up assessment when they were 8 years of
age. A total of 29 previously institutionalized children
(17 from CAUG, 12 from FCG) were lost to follow-up
(the main reasons for attrition were lost contact and re-
fusal to participate). The control group was supple-
mented by the addition of age-matched children
recruited from two local schools. Of the 205 children
who agreed to participate at the 8-year assessment,
we were able to obtain teacher ratings of psychopath-
ology for 195 of them, and 157 children completed
the neuropsychological testing. A total of 146 children
(43 from CAUG, 47 from FCG, 56 from NIG) had data
on both the EF and ADHD measures (see owchart of
participants in Fig. 1). Mean age at testing was 8.56
years (S.D. = 0.40). Descriptive data on demograph-
ic variables for the institutionalized and non-
institutionalized children are presented in Table 1
and show equal gender distributions but signicant
differences in age of testing and ethnicity in the two
Consistent with our previous reports, we did not ob-
serve an intervention effect of foster care on symptoms
of ADHD (t
= 1.13, p= 0.26 for inattention; t
p= 0.94 for impulsivity) or any of the EF indices (their
corresponding pvalues ranged from 0.38 to 0.80) in
this sample. Accordingly, for the remainder of this
paper we consider two groups, children who were
ever institutionalized (EIG, N= 90) and children who
were never institutionalized (NIG, N= 56).
Symptoms of ADHD were assessed through teacher
report using the Health and Behavior Questionnaire
(HBQ; Essex et al. 2002), which has been previously
used in research on institutionalized children (Wiik
et al. 2011). The HBQ has been used extensively with
children of preschool age to adolescence, and has
demonstrated good reliability and convergent and dis-
criminant validity (Essex et al. 2002; Lemery-Chalfant
et al. 2007). Symptoms are rated on a 3-point Likert
scale: 0 (never or not true), 1 (sometimes true)or2
(often or very true), with higher scores indicating ele-
vated levels of symptomatology. ADHD symptoms of
inattention (six items) and impulsivity (nine items) are
We measured EF using the Cambridge Automated
Neuropsychological Test Battery (CANTAB; http://, behavioral tasks that have been
widely used with typically developing children, at-risk
children, children with ADHD, and adults (Nigg, 2001;
Fried et al. 2015). The CANTAB has been validated ex-
tensively on samples of school-age children and has
been found to discriminate well between clinical and
standard populations (Luciana & Nelson, 2002). As
detailed below, four CANTAB subtests (each typically
lasting between 5 and 10 min) were administered
to assess working memory and planning skills.
Additionally, we used a version of the Flanker task
(Eriksen & Schultz, 1979) to assess response inhibition.
Delayed Matching to Sample (DMS) is a short-term
memory task in which the child is presented with a
stimulus pattern and then needs to select a matching
pattern from a series of four patterns shown below
the stimulus. Trials are either simultaneous (both the
stimulus and the four choices are shown on the screen
at the same time), with a 0-s delay (the stimulus disap-
pears just before the choices are presented), or with
a delays of 4000 or 12 000 ms. The main outcome
variables are the number of correct trials and latency
of response for each type of trial.
The Paired Associates Learning (PAL) subtest
assesses spatial working memory and new learning.
Six to eight boxes are presented sequentially on the
screen, with some or all containing a different pattern.
The patterns are then shown again in the middle of the
screen, one at a time and in a randomized order, and
the child has to touch the box that contained the pat-
tern. The difculty increases with the number of pat-
terns contained in the boxes. Outcome variables
include stages completed at rst trial, total stages com-
pleted, and memory score (i.e. number of patterns cor-
rectly located after the rst trial summed across the
stages completed).
Spatial Working Memory (SWM) tests the ability to
retain spatial information across a delay and to ma-
nipulate remembered items in working memory. A
Decits in EF and the link between institutionalization and ADHD 3
number of 38 colored boxes are shown on the screen
and the subject is invited, by process of elimination, to
nd a blue token in each of these boxes and use it to ll
up an empty column on the right of the screen.
Variables of interest are between errors (i.e. number
of times across trials in which the subject revisits a
box in which a token has previously been found), with-
in errors (i.e. number of times within a search in which
the subject revisits an empty box), and strategy (i.e.
presence/absence of organized patterns of search).
The Stockings of Cambridge (SOC) task is a plan-
ning task derived from the Tower of London test
(Shallice, 1982). The child views a set of three hanging
stockings on the top of the screen that contain colored
circles in a given order and another set of stockings on
the lower half of the screen containing the same circles
but positioned differently across the stockings. The
Fig. 1. Flow chart of participants.
Table 1. Descriptive statistics on demographic information
(N= 90)
(N= 56) Group difference
Age at testing,
years (S.D.)
8.63 8.44 t= 2.90; p= 0.004
Male 43 26 N.S.
Female 47 30
Romanian 46 50 χ
(2) = 24.73, p< 0.001
Roma 33 4
11 2
EIG, Ever institutionalized group; NIG, never institutiona-
lized group; N.S., not signicant.
4F. Tibu et al.
child is instructed to move the circles in the lower dis-
play to copy the upper model using as few moves as
possible. The difculty of the trials increases gradually
from two-move problems to more complex models that
require ve moves to solve. Key outcomes are number
of trials solved in minimum moves, mean number of
moves for each level of difculty, and initial and sub-
sequent thinking times.
The Flanker task assesses the childrens capacity to
respond to target stimuli in the context of other dis-
tracting stimuli. A series of ve arrows (pointing to
the left or right) are presented to the child on a com-
puter screen. The child is instructed to focus solely
on the central arrow, which always appears anked
by two more arrows on either side, and to press as
quickly and as accurately as possible the left button
on a pad when the target points to the left, and the
right button when the arrow is directed to the right.
The two pairs of distracting arrows between which
the target arrow is situated point to either the same dir-
ection as the target (congruent trials, <<<<< and >>>>>)
or the opposite (incongruent trials, >><>> and <<><<).
We collected both response accuracy and reaction
time (RT) during congruent and incongruent trials.
Differences in RT between incongruent and congruent
trials (known as the Flanker effect) are thought to
reect response inhibition (Fan et al. 2002).
All children were accompanied to the laboratory by
their main caregiver to complete the procedures.
Informed consent was obtained from the caregiver
and written approvals to participate were collected
from the local authority representatives prior to the
start of the study for the institutionalized and foster
care children whose legal guardians were not their bio-
logical parents. The child was invited to one of the
study rooms to complete the CANTAB in the presence
of a researcher who provided standard instructions. In
a separate session, the child was asked to complete the
Flanker task along with other procedures; however,
due to logistical reasons, a total of 47 children (16
from CAUG, 10 from FCG, 21 from NIG) completed
both the CANTAB and the Flanker tasks during the
same visit. Finally, the research team contacted the pri-
mary school teachers and asked them to complete the
teacher version of the HBQ.
Statistical analysis
We investigated whether impaired EF task perform-
ance associated with exposure to institutionalization
was responsible for the elevated rates of inattention
and impulsivity among previously institutionalized
children relative to community controls using standard
tests of statistical mediation. To provide evidence for
mediation, four criteria must be met (Baron & Kenny,
1986; MacKinnon et al. 2002). First, an association be-
tween the exposure and outcome of interest must be
established. Here, we examined differences in symp-
toms of ADHD using univariate analysis of variance
(ANOVA) with group (EIG and NIG) as a between-
subjects factor. Because previous research suggests
that EF may be differentially associated with subtypes
of ADHD (Martel et al. 2007; Brocki et al. 2010), we
examined symptoms of inattention and impulsivity
as separate outcomes.
Second, the exposure must be associated with the
putative mediator. We examined group differences in
EF using univariate ANOVAs with group as a
between-subjects factor. We examined performance
on working memory (DMS, PAL, SWM), response in-
hibition (Flanker), and planning (SOC) tasks. Third,
the mediator must be associated with the outcome.
Here, we examined the association between EF and
ADHD symptoms using linear regression.
The nal critical test of mediation involves the de-
gree of attenuation in the association between the ex-
posure and outcome in a model that includes the
mediator. If this association is attenuated signicantly,
a signicant indirect effect of the exposure on the
outcome through the mediator exists, establishing
evidence for mediation (Baron & Kenny, 1986;
MacKinnon et al. 2002). Here, we tested the signicance
of the mediator using a bootstrapping approach that
provides bias corrected condence intervals and
allows multiple mediators (i.e. measures of EF) to be
examined in one model (Preacher & Hayes, 2008).
Condence intervals that do not include zero indicate
signicant mediation. Age and gender were included
as covariates in all analyses, and statistical signicance
was evaluated at the 0.05 level, using two-sided tests.
Institutionalization and ADHD symptomatology
Mean scores of inattention and impulsivity were exam-
ined between the two groups using ANOVA and are
presented in Table 2. Children with history of institu-
tionalization had signicantly higher inattention
=49.01, p<0.001), and impulsivity (F
p<0.001), than the community controls (Table 2).
Institutionalization and executive functioning
ANOVA was conducted to examine whether the two
groups differed on the variables of interest from each
of the ve tasks. Results are presented in Table 3 and
show that children in the EIG performed signicantly
more poorly than NIG children on multiple
Decits in EF and the link between institutionalization and ADHD 5
dimensions of executive functioning as measured by
our CANTAB battery and the Flanker task. Children
exposed to institutional rearing had signicantly
lower accuracy on the longest delay trials of the DMS
task (F
= 10.89, p= 0.001), a lower number of PAL
stages completed on rst trial (F
= 7.78, p= 0.006),
lower PAL rst trial memory scores (F
= 10.90,
p= 0.001), lower SWM strategy scores (F
= 10.73,
p= 0.001), higher number of SWM between errors
= 17.40, p<0.001), lower response inhibition in
the Flanker task (F
= 10.05, p= 0.002), and fewer
problems solved in minimum moves on the SOC task
= 6.36, p= 0.013).
Associations between inattention and impulsivity and
the EF indices are reported in Table 4 (see Appendix
Table A1 for correlational associations amongst all
variables of interest). Inattention was signicantly
associated with several aspects of working memory
performance. These included the number of PAL
stages completed on rst trial, PAL rst trial memory
score, SWM strategy score, and SWM between errors.
Inattention was also marginally negatively associated
with accuracy in the longest delay trials of the DMS,
another index of working memory. Likewise, inatten-
tion was associated with response inhibition measured
in the Flanker task. Last, a marginal association was
observed between inattention and planning as
assessed by SOC problems solved in minimum
moves. All associations were in the expected direction:
elevated levels of inattention symptoms associated
with decreased EF performance.
Similar to our ndings with inattention symptoms,
we observed signicant associations between impulsiv-
ity and PAL rst trial memory score, SWM strategy
score, SWM between errors and a marginally signi-
cant association between impulsivity and accuracy in
the longest delay trials of the DMS. Impulsivity was
also associated with response inhibition in the Flanker
task and the number of SOC problems solved in min-
imum moves. No association was observed between
impulsivity and PAL stages completed on rst trial.
Mediation analysis
In order to assess whether indices of EF explain the
relations between early deprivation and later ADHD
symptomatology, we conducted two multiple medi-
ation analyses separately for inattention and impulsiv-
ity. We separately tested mediation for working
memory, response inhibition and planning by entering
the measures of these constructs that were associated
with both institutionalization and the outcome (i.e. in-
attention and impulsivity).
The total effect of early institutionalization in
predicting inattention was signicant (B=1.80, p<
0.001) and was attenuated by 15.6% with the inclusion
of the working memory indices in the model (i.e. DMS
percent accuracy 12 000 ms., PAL stages completed on
rst trial, PAL rst trial memory score, SWM strategy
score, and SWM between errors total, B=1.52, p<
0.001; Fig. 2). The indirect effect of institutionalization
on inattention was signicant [95% condence interval
(CI) 0.56 to 0.06]. By contrast, the indirect effects of
institutionalization on inattention when the inhibition
or planning indices were added to the model were
not statistically signicant (95% CIs 0.28 to 0.00;
0.19 to 0.03 respectively).
Similarly, the total effect of institutionalization in
predicting impulsivity was signicant (B=2.23, p<
0.001) and was attenuated by 16.6% with the inclusion
of working memory indices in the model (B=1.86,
p<0.001). The indirect effect of institutionalization
was statistically signicant (95% CI 0.80 to 0.04).
Likewise, the total effect of institutionalization on
impulsivity was signicant (B=2.24, p<0.001) and
was attenuated by 9% with the inclusion of the
Flanker index of response inhibition (B=2.04, p<
0.001; Fig. 3). The indirect effect of institutionalization
on impulsivity through response inhibition was signi-
cant (95% CI 0.52 to 0.03). By contrast, the indirect
effect of institutionalization in the prediction of impul-
sivity when the planning index was added to the
model was not statistically signicant (95% CI 0.40
to 0.01). Together, these ndings suggest that inatten-
tion and impulsivity associated with exposure to insti-
tutionalization are partially explained by decits in
working memory and response inhibition, but not
planning abilities.
Specicity of associations
In order to ascertain that decits in EF represent a
mechanism which specically explains symptoms of
Table 2. Teacher reports of ADHD symptoms in the EIG and NIG
EIG (N= 96) NIG (N= 99) Group difference
Mean S.D. Mean S.D.Fpvalue
Inattention 5.42 3.35 2.31 2.83 49.01* <0.001
Impulsivity 7.61 5.29 3.73 4.09 32.87* <0.001
ADHD, Attention decit hyperactivity disorder; EIG, ever
institutionalized group; NIG, never institutionalized group.
*Signicant at the 0.05 level, two-sided test; analyses con-
trol for age and gender.
6F. Tibu et al.
ADHD as opposed to other forms of psychopathology
in previously institutionalized children, we ran add-
itional analyses with the outcome scales of internaliz-
ing (e.g. anxiety and depression) and externalizing
(i.e. oppositional/deant and conduct) symptoms of
the HBQ. Institutionalization was indeed associated
with elevations in both of these scale scores on the
HBQ (details not presented but available upon re-
quest). However, disruptions in EF did not mediate
the association of institutionalization with any form
of psychopathology other than ADHD, which supports
our hypothesis that EF decits are a pathway linked
specically to ADHD symptoms.
The purpose of the current study was to test whether
decits in EF were a mechanism linking early psycho-
social deprivation to ADHD symptoms at age 8 years.
The association between early institutionalization and
ADHD symptoms was partially explained by decits
in working memory (for both inattention and impul-
sivity) and response inhibition (for impulsivity only),
but was not accounted for by planning ability. These
ndings build on previous reports describing the path-
ways through which institutionalization inuences
mental health outcomes in children and extends
Table 3. EF abilities in the EIG and NIG children
EIG (N= 90) NIG (N= 57) Group difference
Mean S.D. Mean S.D.Fpvalue
Percent accuracy 4000 ms 57.39 23.76 62.81 19.06 2.09 0.15
Percent accuracy 12 000 ms 51.82 25.49 65.97 24.77 10.89* 0.001
Stages completed on 1st trial 4.89 1.23 5.44 1.10 7.78* 0.006
First trial memory score 16.32 4.65 18.70 3.76 10.90* 0.001
Strategy score 39.45 2.54 37.63 4.43 10.73* 0.001
Between errors total 67.36 12.85 57.67 15.83 17.40* <0.001
RT incongruent RT congruent 0.05 0.06 0.09 0.09 10.05* 0.002
Problems solved in minimum moves 5.55 2.02 6.35 1.72 6.36* 0.013
EF, Executive functioning; EIG, ever institutionalized group; NIG, never institutionalized group; DMS, Delayed Matching to
Sample; PAL, Paired Associates Learning; SWM, Spatial Working Memory; RT, reaction time; SOC, Stockings of Cambridge;
*Signicant at the 0.05 level, two-sided test; analyses control for age and gender.
DMS statistics are reported only on those subjects who had scores which were greater than expected by chance in the
0-ms delay trials.
Table 4. Associations between ADHD symptoms and EF indices at
8 years
Inattention Impulsivity
Working memory
DMS % accuracy 12 000 ms
0.17 0.059 0.16 0.07
PAL stages completed on
1st trial
0.24 0.004 0.11 0.16
PAL rst trial memory score 0.39 <0.001 0.25 0.002
SWM strategy score 0.18 0.037 0.21 0.013
SWM between errors total 0.30 <0.001 0.20 0.016
Response inhibition
Flanker RT incongruent
RT congruent
0.21 0.012 0.24 0.004
SOC problems solved in
minimum moves
0.15 0.079 0.19 0.018
ADHD, Attention decit hyperactivity disorder; EF, ex-
ecutive functioning; DMS, Delayed Matching to Sample;
PAL, Paired Associates Learning; SWM, Spatial Working
Memory; RT, reaction time; SOC, Stockings of Cambridge.
Analyses control for age and gender.
DMS statistics are reported only on those subjects who
had scores which were greater than expected by chance in
the 0-ms delay trials.
Decits in EF and the link between institutionalization and ADHD 7
previous research by highlighting the importance of
working memory and inhibition as neurodevelopmen-
tal mechanisms involved in the association of institu-
tional rearing with ADHD symptoms.
The association between institutionalization and
symptoms of ADHD observed here are consistent
with results from a number of other studies (e.g.
Kreppner et al. 2001; Stevens et al. 2008; Wiik et al.
2011), as well as our own work in the BEIP when the
children were assessed at earlier ages (Zeanah et al.
2009). Elevated ADHD symptomatology associated
with early institutionalization is likely to result from
decits in neurodevelopmental processes. Consistent
with this hypothesis, poorer performance on EF tasks
has been observed in prior studies of previously insti-
tutionalized children (e.g. Colvert et al. 2008; Pollak
et al. 2010; Merz & McCall, 2011; Hostinar et al. 2012;
Merz et al. 2013). The novelty of the current investiga-
tion is that it is the rst to demonstrate that one mech-
anism linking early institutionalization to ADHD is
disruption in working memory and response inhib-
ition. To best of our knowledge, only one report (i.e.
Colvert et al. 2008) has tested mediation and suggested
that inhibition might play a mediating role in this link,
but the analyses showed only a trend that failed to at-
tain statistical signicance. Here, we found that re-
sponse inhibition served as a signicant mediator of
the association between institutionalization and impul-
sivity, a specic cluster of ADHD symptomatology.
Previous investigations in the BEIP and other sam-
ples of children adopted from Eastern Europe have
identied several neurobiological factors that partially
or fully mediate the association between institution-
alization and the incidence of ADHD. In our own
sample, delayed cortical maturation manifesting in
atypical EEG frequency band signals and reduced cor-
tical thickness in multiple brain regions has been found
to partially mediate the link from early deprivation to
ADHD at 4½ and 8 years (McLaughlin et al. 2010a,
2014). In contrast to those ndings, the current paper
explores the mediating pathway of speciccognitive
functions, namely working memory, response inhib-
ition, and planning. Our ndings point to specic cog-
nitive functions that link institutionalization to ADHD,
but not common to other forms of externalizing psy-
chopathology or to internalizing psychopathology.
We also nd specicity in the specic domains of EF
that are involved in this association. Two ndings are
Fig. 2. Model of the association between institutionalization and symptoms of inattention at 8 years as mediated by indices of
working memory
. ADHD, attention-decit/hyperactivity disorder. [
Unstandardized coefcients are shown for the direct and
indirect (in parentheses, with mediators included) regression models; *p< 0.001.]
Fig. 3. Models of the associations between institutionalization and symptoms of impulsivity at 8 years as mediated by indices
of working memory (solid lines) and response inhibition (dotted lines)
. ADHD, Attention decit hyperactivity disorder.
Unstandardized coefcients are shown for the direct and indirect (in parentheses, with mediators included) regression
models; *p< 0.001.]
8F. Tibu et al.
notable. First, children raised in institutions exhibited
decits in working memory only during the most dif-
cult trials of the DMS task that required holding a
stimulus in mind for the longest period of time.
Although previously institutionalized children per-
formed reasonably well at maintaining a stimulus in
working memory for short periods of time, maintain-
ing this representation over time was more challenging
for them; this pattern suggests that more complex
aspects of working memory such as updating or
manipulating information may be most impacted
by institutional rearing. Second, our nding that the
association between institutional rearing and ADHD
was mediated specically by working memory and in-
hibition, but not by planning, highlights that while
many aspects of cognitive and neural function and
neural structure are impacted by institutionalization,
they may not all contribute equally to risk for
ADHD. Indeed, it is by identifying specic pathways
of risk, as we do here, that we are most likely to de-
velop interventions to remediate the effects of institu-
tional rearing on specic mental health outcomes,
including ADHD. Our ndings suggest that although
children exposed to institutional rearing exhibit decits
in multiple forms of EF, the association with ADHD
symptoms is explained primarily by decits in work-
ing memory and response inhibition. Given the sample
size, and the fact that our main effect differs subtly
from previous ndings, because we controlled for
age and gender in the analysis, it is possible that plan-
ning does play a role in ADHD following institutional-
ization, albeit, one which was too small for us to
observe here. The non-signicant mediating effect of
planning needs to be replicated in future investigations
before rm conclusions are drawn.
These ndings are consistent with previous work
that demonstrates that performance on the SWM sub-
test, but not the planning subtest of the CANTAB pre-
dicts symptom severity in adolescents with ADHD
(Coghill et al. 2014). One possible explanation for this
observation is that working memory might represent
a more basic aspect of EF that scaffolds the develop-
ment of more complex cognitive functions and that,
when disrupted, has more severe downstream effects
on cognition and behavior, including symptoms of in-
attention and impulsivity.
Similarly, our nding that symptoms of impulsivity
emerge partly as a result of poor response inhibition in
children who experienced psychosocial neglect early in
life is consistent with the nding that good response
inhibition functions as an index of resilience following
exposure to environmental adversities (Nigg et al. 2007;
McDermott et al. 2013). The fact that we do not see the
same association with inattention may be related to the
selective importance of response inhibition in
predicting symptoms of motor impulsivity and hyper-
activity (Barkley, 2001). Finally, within this study, the
neuropsychological prole of children who have
ADHD following exposure to institutionalization is
very similar to the proles of children who receive a
diagnosis of ADHD having been raised in more typical
environments. Thus it is possible that exposure to insti-
tutionalization increases risk for ADHD via its impact
on the same neural structures and functions that
underlie dysfunction in ADHD more generally.
The results in the current study should be inter-
preted in view of several limitations. First, our ndings
are based on EF and ADHD data collected at the same
point in development, this rst point that EF was
assessed in the study. This suggests that our ndings
could also reect earlier-onset ADHD predicting dis-
ruptions in EF, rather than the reverse. However,
ADHD symptoms at age 4½ years were assessed in
the BEIP using a parent-reported interview, and we
observed no associations between earlier ADHD
symptoms and EF at age 8 years. This provides further
support for our interpretations of these associations at
age 8 years. Because the BEIP is a longitudinal study,
we hope in the future to make use of our repeated mea-
sures design to examine how EF predicts changes over
time in ADHD. Second, psychopathology was only
assessed using teacher questionnaires; previous studies
have made use of psychiatric interviews and/or paren-
tal reports in obtaining child psychopathology data.
However, ADHD behaviors frequently manifest in
the school setting, and teacher reports provide a stan-
dardized method of reporting ADHD symptoms as
compared to caregiver reports in this sample, given
variation in the length and quality of caregiver rela-
tionships among children with and without exposure
to institutional rearing. Teachers also have a unique
perspective in having substantial amounts of time in
which to observe children at a particular developmen-
tal period and to evaluate individual differences.
Nevertheless, it is possible that symptoms observed
at school are only part of the problematic behaviors
shown in other environments, and that other infor-
mants and/or the use of diagnoses might reect more
adequately the manifestations of the problem. Finally,
we were not able to account for the possible inuence
of other factors (e.g. prenatal, genetic risks, or medical
illnesses during the gestational or early infancy peri-
ods, and socioeconomic status) that might have played
a direct or interactive role in the link between early de-
privation and ADHD and which should be examined
in future studies.
This study identied working memory and response
inhibition as partial mediators of the association be-
tween institutional rearing and ADHD symptoms at
8 years of age in children who were exposed to severe
Decits in EF and the link between institutionalization and ADHD 9
psychosocial deprivation in orphanages in Romania.
The current ndings have the potential to inform de-
velopmental specialists on some of the early neurode-
velopmental pathways to psychopathology so that
intervention can be effectively targeted in order to
reduce risks and promote adaptive developmental
outcomes for children exposed to adverse early envir-
onments. Specically, our ndings suggest that inter-
ventions designed to improve working memory and
inhibition (Klingberg et al. 2005; Johnstone et al. 2010)
could have a benecial effect on ADHD symptoms
among children exposed to institutional rearing.
This research was supported by a grant from the John
D. and Catherine T. MacArthur Foundation Research
Network on Early Experience and Brain Development
(Charles A. Nelson, Network Chair), the National
Institutes of Health (to C.A.N.; 1R01MH091363-01),
and research support from the Binder Foundation (to
C.A.N.). These funders provided support for all data
collection and analysis. We thank Elizabeth Furtado
for overseeing the Bucharest Early Intervention
Project and all the laboratory staff in Romania (Anca
Radulescu, Nicoleta Corlan, Nadia Radu, Carmen
Iuga and Iuliana Dobre) for collecting the data and
maintaining contact with the families. We also thank
the caregivers and children who participated in this
Declaration of Interest
Barkley RA (1997). Behavioral inhibition, sustained attention,
and executive function: constructing a unied theory of
ADHD. Psychological Bulletin 121,6594.
Barkley RA (2001). The inattentive type of ADHD as a
distinct disorder: what remains to be done. Clinical
Psychology: Science and Practice 8, 489493.
Baron RM, Kenny DA (1986). The moderator-mediator
variable distinction in social psychological research:
conceptual, strategic, and statistical considerations. Journal
of Personality and Social Psychology 51, 11731182.
Biederman J, Milberger S, Faraone SV, Kiely K, Guite J,
Mick E, Ablon S, Warburton R, Reed E (1995).
Family-environment risk factors for attention-decit
hyperactivity disorder. A test of Rutters indicators of
adversity. Archives of General Psychiatry 52, 464470.
Bos KJ, Fox N, Zeanah CH, Nelson CA (2009). Effects of early
psychosocial deprivation on the development of memory
and executive function. Frontiers in Behavioral Neuroscience
3, 16.
Brocki K, Eninger L, Thorell L, Bohlin G (2010).
Interrelations between executive function and symptoms of
hyperactivity/impulsivity and inattention in preschoolers: a
two year longitudinal study. Journal of Abnormal Child
Psychology 38, 163171.
Coghill DR, Hayward D, Rhodes SM, Grimmer C,
Matthews K (2014). A longitudinal examination of
neuropsychological and clinical functioning in boys with
attention decit hyperactivity disorder (ADHD):
improvements in executive functioning do not explain
clinical improvement. Psychological Medicine 44,
Colvert E, Rutter M, Kreppner J, Beckett C, Castle J,
Groothues C, Hawkins A, Stevens S, Sonuga-Barke EJ
(2008). Do theory of mind and executive function decits
underlie the adverse outcomes associated with profound
early deprivation? Findings from the ERA study. Journal of
Abnormal Child Psychology 36, 10571068.
DePrince AP, Weinzierl KM, Combs MD (2009). Executive
function performance and trauma exposure in a community
sample of children. Child Abuse and Neglect 33, 353361.
Eriksen CW, Schultz DW (1979). Information processing in
visual search: a continuous ow conception and
experimental results. Perception & Psychophysics 25, 249263.
Essex MJ, Boyce WT, Goldstein LH, Armstrong JM,
Kraemer HC, Kupfer DJ (2002). The conuence of mental,
physical, social, and academic difculties in middle
childhood. II. Developing the MacArthur health and
behavior questionnaire. Journal of the American Academy of
Child and Adolescent Psychiatry 41, 588603.
Fair DA, Bathula D, Nikolas MA, Nigg JT (2012). Distinct
neuropsychological subgroups in typically developing
youth inform heterogeneity in children with ADHD.
Proceedings of the National Academy of Sciences USA 109,
Fan J, McCandliss BD, Sommer T, Raz A, Posner MI
(2002). Testing the efciency and independence of
attentional networks. Journal of Cognitive Neuroscience 14,
Fried R, Hirshfeld-Becker D, Petty C, Batchelder H,
Biederman J (2015). How informative is the CANTAB to
assess executive functioning in children with ADHD? A
controlled study. Journal of Attention Disorders 19, 468475.
Halperin JM, Schulz KP (2006). Revisiting the role of the
prefrontal cortex in the pathophysiology of attention-
decit/hyperactivity disorder. Psychological Bulletin 132,
Hostinar CE, Stellern SA, Schaefer C, Carlson SM, Gunnar
MR (2012). Associations between early life adversity and
executive function in children adopted internationally from
orphanages. Proceedings of the National Academy of Sciences
USA 109, 1720817212.
Humphreys KL, Gleason MM, Drury SS, Miron D, Nelson
CA, Fox NA, Zeanah CH (2015). Effects of institutional
rearing and foster care on psychopathology at age 12 years
in Romania: follow-up of an open, randomised controlled
trial. Lancet Psychiatry 7, 625634.
10 F. Tibu et al.
Johnstone SJ, Roodenrys S, Phillips E, Watt AJ, Mantz S
(2010). A pilot study of combined working memory and
inhibition training for children with AD/HD. Attention
Decit Hyperactivity Disorders 2,3142.
Kessler R, Adler L, Barkley R, Biederman J, Conners CK,
Demler O, Faraone S, Greenhill L, Howes M, Secnik K,
Spencer T, Ustun B, Walters E, Zaslavsky A (2006). The
prevalence and correlates of adult ADHD in the United
States: results from the National Comorbidity Survey
Replication. American Journal of Psychiatry 163, 716723.
Klingberg T, Fernell E, Olesen PJ, Johnson M, Gustafsson P,
Dahlström K, Gillberg C, Forssberg H, Westerberg H
(2005). Computerized training of working memory in
children with ADHD a randomized, controlled trial.
Journal of the American Academy of Child and Adolescent
Psychiatry 44, 177186.
Kreppner JM, OConnor TG, Rutter M,English &
Romanian Adoptees (ERA) Study Team (2001). Can
inattention/overactivity be an institutional deprivation
syndrome? Journal of Abnormal Child Psychology 29, 513528.
LemeryChalfant K, Schreiber JE, Schmidt NL, Van Hulle
CA, Essex MJ, Goldsmith HH (2007). Assessing
internalizing, externalizing, and attention problems in
young children: validation of the MacArthur HBQ. Journal
of the American Academy of Child & Adolescent Psychiatry 46,
Loman MM, Johnson AE, Westerlund A, Pollak SD, Nelson
CA, Gunnar MR (2013). The effect of early deprivation on
executive attention in middle childhood. Journal of Child
Psychology and Psychiatry 54,3745.
Luciana M, Nelson CA (2002). Assessment of
neuropsychological function in children through the
Cambridge Neuropsychological Testing Automated Battery
(CANTAB): normative performance in 4 to 12 year-olds.
Developmental Neuropsychology 22, 595624.
MacKinnon DP, Lockwood CM, Hoffman JM, West SG,
Sheets V (2002). A comparison of methods to test
mediation and other intervening variable effects.
Psychological Methods 7,83104.
Martel M, Nikolas M, Nigg JT (2007). Executive function in
adolescents with ADHD. Journal of the American Academy of
Child and Adolescent Psychiatry 46, 14371444.
Martinussen R, Hayden J, Hogg-Johnson S, Tannock R
(2005) A meta-analysis of working memory impairments in
children with ADHD. Journal of the American Academy of
Child and Adolescent Psychiatry 44, 377384.
McDermott JM, Troller-Renfree S, Vanderwert R, Nelson
CA, Zeanah CH, Fox NA (2013). Psychosocial deprivation,
executive functions and the emergence of socio-emotional
behavior problems. Frontiers in Human Neuroscience 7, 167.
McLaughlin KA, Fox NA, Zeanah CH, Sheridan MA,
Marshall P, Nelson CA (2010a). Delayed maturation in
brain electrical activity partially explains the association
between early environmental deprivation and symptoms of
attention-decit/hyperactivity disorder. Biological Psychiatry
68, 329336.
McLaughlin KA, Green JG, Gruber MJ, Sampson NA,
Zaslavsky AM, Kessler RC (2010b). Childhood adversities
and adult psychiatric disorders in the national comorbidity
survey replication II: associations with persistence of
DSM-IV disorders. Archives of General Psychiatry 67,
McLaughlin KA, Sheridan MA, Winter W, Fox NA, Zeanah
CH, Nelson CA (2014). Widespread reductions in cortical
thickness following severe early-life deprivation: a
neurodevelopmental pathway to attention-decit/
hyperactivity disorder. Biological Psychiatry 76, 629638.
Merz EC, McCall RB (2011). Parent ratings of executive
functioning in children adopted from psychosocially
depriving institutions. Journal of Child Psychology and
Psychiatry 52, 537546.
Merz EC, McCall RB, Groza V (2013). Parent-reported
executive functioning in post-institutionalized children: a
follow-up study. Journal of Clinical Child & Adolescent
Psychology 42, 726733.
Nelson CA, Fox NA, Zeanah CH (2014). Romanias Abandoned
Children: Deprivation, Brain Development, and the Struggle
for Recovery. Harvard University Press: Cambridge,
Niendam TA, Laird AR, Ray KL, Dean YM, Glahn DC,
Carter CS (2012). Meta-analytic evidence for a
superordinate cognitive control network subserving diverse
executive functions. Cognitive, Affective and Behavioral
Neuroscience 12, 241268.
Nigg JT (2001). Is ADHD a disinhibitory disorder?
Psychological Bulletin 127, 571598.
Nigg JT, Nikolas M, Friderici K, Leeyoung P, Zucker RA
(2007). Genotype and neuropsychological response
inhibition as resilience promoters for ADHD, ODD, and CD
under conditions of psychosocial adversity. Development
and Psychopathology 19, 767786.
Pears KC, Fisher PA, Bruce J, Kim HK, Yoerger K (2010).
Early elementary school adjustment of maltreated children
in foster care: the role of inhibitory control and caregiver
involvement. Child Development 81, 15501564.
Pollak SD, Nelson CA, Schlaak MF, Roeber BJ, Wewerka
SS, Wiik KL, Frenn KA, Loman MM, Gunnar MR (2010).
Neurodevelopmental effects of early deprivation in
postinstitutionalized children. Child Development 81,
Preacher KJ, Hayes AF (2008). Asymptotic and resampling
strategies for assessing and comparing indirect effects in
multiple mediator models. Behavior Research Methods 40,
Rutter M, Kreppner JM, OConnor TG,The English
Romanian Adoptees (ERA) Study Team (2001). Specicity
and heterogeneity in childrens responses to profound
institutional privation. British Journal of Psychiatry 17,
Rutter M, Sonuga-Barke E, Beckett C, Castle J, Kreppner J,
Kumsta R, Schlotz W, Stevens S, Bell C, Gunnar M (2010).
Deprivation-specic psychological patterns: effects of
institutional deprivation. Monographs of the Society for
Research in Child Development 75,1242.
Schoemaker K, Bunte T, Wiebe SA, Espy KA, Dekovic M,
Matthys W (2012). Executive function decits in preschool
children with ADHD and DBD. Journal of Child Psychology
and Psychiatry 53, 111119.
Decits in EF and the link between institutionalization and ADHD 11
Sergeant J (2000). The cognitive-energetic model: an empirical
approach to attention-decit hyperactivity disorder.
Neuroscience and Biobehavioral Reviews 24,712.
Shallice T (1982). Specic impairments in planning.
Philosophical Transactions of the Royal Society of London 298,
Slopen N, McLaughlin KA, Fox NA, Zeanah CH, Nelson CA
(2012). Alterations in neural processing and psychopathology
in children raised in institutions. Archives of General Psychiatry
69, 10221030.
Sonuga-Barke E, Dalen L, Daley D, Remington B (2002). Are
planning, working memory, and inhibition associated with
individual differences in preschool ADHD symptoms?
Developmental Neuropsychology 21, 255272.
Spencer TJ, Biederman J, Mick E (2007). Attention-decit/
hyperactivity disorder: diagnosis, lifespan, comorbidities,
and neurobiology. Journal of Pediatric Psychology 32,631642.
Stevens SE, Sonuga-Barke E, Kreppner JM, Beckett C,
Castle J, Colvert E, Groothues C, Hawkins A, Rutter M
(2008). Inattention/overactivity following early severe
institutional deprivation: presentation and associations in
early adolescence. Journal of Abnormal Child Psychology 36,
Taylor E, Rogers JW (2005). Practitioner review: early
adversity and developmental disorders. Journal of Child
Psychology and Psychiatry 46, 451467.
UNICEF (2010). At Home or in a Home? Formal care and
adoption of children in Eastern Europe and Central Asia.
UNICEF Geneva, Swizerland.
Wiik KL, Loman MM, Van Ryzin MJ, Armstrong JM, Essex
MJ, Pollak SD, Gunnar MR (2011). Behavioral and
emotional symptoms of post-institutionalized children in
middle childhood. Journal of Child Psychology and Psychiatry
Willcutt EG, Doyle AE, Nigg JT, Faraone SV, Pennington BF
(2005). Validity of the executive function theory of
attention-decit/hyperactivity disorder: a meta-analytic
review. Biological Psychiatry 57, 13361346.
Zeanah CH, Egger HL, Smyke AT, Nelson CA, Fox NA,
Marshall PJ, Guthrie D (2009). Institutional rearing and
psychiatric disorders in Romanian preschool children.
American Journal of Psychiatry 166, 777785.
Zeanah CH, Fox NA, Nelson CA (2012). The Bucharest Early
Intervention Project: case study in the ethics of mental
health research. Journal of Nervous and Mental Disease 200,
Zeanah CH, Nelson CA, Fox NA, Smyke AT, Marshall P,
Parker S, Koga S (2003). Designing research to study
the effects of institutionalization on brain and
behavioral development: the Bucharest Early
Intervention Project. Developmental Psychopathology 15,
12 F. Tibu et al.
Appendix Table A1. Pearson correlations among study variables
Inattention Impulsivity
DMS percent
accuracy at
DMS percent
accuracy at
4000 ms
DMS percent
accuracy at
12 000 ms
PAL stages
on rst trial
PAL rst
trial memory
RT incongruent
RT congruent
SOC problems
solved in
Inattention 1 0.75*** 0.32*** 0.16 0.20* 0.25** 0.35*** 0.18* 0.30*** 0.22** 0.17*
Impulsivity 1 0.27*** 0.09 0.20* 0.13 0.28*** 0.21** 0.20* 0.25** 0.23**
DMS percent accuracy at
1 0.16 0.03 0.11 0.19* 0.04 0.09 0.05 0.12
DMS percent accuracy at
4000 ms
1 0.13 0.26*** 0.31*** 0.13 0.17* 0.03 0.01
DMS percent accuracy at
12 000 ms
1 0.17* 0.24** 0.03 0.21** 0.10 0.14
PAL stages completed on
rst trial
1 0.79*** 0.03 0.32*** 0.02 0.19*
PAL rst trial memory
10.08 0.39*** 0.12 0.28***
SWM strategy 1 0.42*** 0.19* 0.24**
SWM between errors 1 0.20* 0.41***
RT incongruent RT
1 0.12
SOC problems solved in
minimum moves
DMS, Delayed Matching to Sample; PAL, Paired Associates Learning; SWM, Spatial Working Memory; RT, reaction time; SOC, Stockings of Cambridge.
* Correlation is signicant at the 0.05 level (two-tailed).
** Correlation is signicant at the 0.01 level (two-tailed).
*** Correlation is signicant at the 0.001 level (two-tailed).
Decits in EF and the link between institutionalization and ADHD 13
... All articles were published in English in peer-reviewed journals. Characteristics of the included studies are presented in detail in Appendix B. One study was a population-based longitudinal study (Mills et al., 2011), four were longitudinal studies of at-risk samples (e.g., low-income/ disadvantaged families, high-risk sampling strategy, children at risk of maltreatment; Enlow et al., 2012;Font & Berger, 2015;Harpur et al., 2015;Jaffee et al., 2007), and two studies were conducted in samples of children adopted from Romanian institutions (Beckett et al., 2006;Tibu et al., 2016). In the remaining studies, community samples of maltreated children were recruited. ...
... In most studies, the control group was matched to the sociodemographic characteristics of the trauma group so that there were no, or very few, differences between the groups in terms of children's age, gender, and ethnicity, parent's education and families' SES, which was a methodological strength of the studies reviewed. The predominant ethnic group in trauma and control groups was Caucasian in six studies (Beckett et al., 2006;Fitch et al., 1976;Mills et al., 2011;Noll et al., 2010;Tibu et al., 2016;Weller et al., 2015) and African American in three studies (Cheatham et al., 2010;Font & Berger, 2015;Harpur et al., 2015). Ethnic group distribution was not specified for trauma and control groups separately in the four remaining studies (Enlow et al., 2012;Jaffee et al., 2007;Manly et al., 2013;Rieder & Cicchetti, 1989). ...
... The majority of studies did not report precise information regarding children's behavioral and mental health problems, current placement, care history, interventions, and duration of trauma, and no study reported the occurrence of a PTSD diagnosis or symptoms. Tibu et al. (2016) reported that approximately 20% of children with trauma had ADHD, whereas Jaffee et al. (2007) reported that approximately a quarter of children with trauma had well-adjusted temperaments. Weller et al. (2015) reported internalizing and externalizing symptoms among children with trauma. ...
Full-text available
Longitudinal studies have shown that children with complex trauma (i.e., exposure to multiple or repeated traumatic events of an interpersonal nature) have poorer cognitive outcomes later in life than children without complex trauma. This association may be moderated by the timing of the trauma, which may explain, in part, some heterogeneity in the findings reported across previous investigations. The objective of the systematic review and meta-analyses was to compare the cognitive outcomes of children with complex trauma and controls and to explore whether the timing of trauma (i.e., its onset and recency) moderated this association. Electronic databases (APA PsycNET, Pubmed Central, ERIC, CINAHL, Embase) and gray literature were systematically searched. To be included, studies had to (1) have a longitudinal design, (2) comprise children with complex trauma and controls, and (3) include a cognitive assessment. Thirteen studies were identified. Meta-analyses were conducted to compare children with complex trauma and controls, while subgroup analyses and meta-regressions explored the impact of potential moderators. Children with complex trauma had poorer overall cognitive functioning than controls, and the timing of trauma (early onset and, to a greater extent, recency of trauma) moderated this association. Thus, findings suggest that children with complex trauma are at risk of cognitive difficulties quickly after trauma exposure. As such, systematic neuropsychological assessment and interventions supporting the optimal development of cognitive functioning among children with complex trauma should be investigated to determine whether prompt interventions lead to better cognitive functioning.
... It has been well documented that parents who are under-resourced have higher rates of adversity exposures, increased exposure to stress, and lower parental involvement, all of which are likely to increase risks for psychopathology [60][61][62][63][64][65][66]. In particular, an emerging literature associating low SES and other forms of adversity exposure with poor executive functions (EF) and high risk for ADHD have led to a theoretical model of the impact of early experience on EF and externalizing psychopathology [64,65,67]. ...
... While twin, family, and adoption studies have demonstrated a strong heredity component in ADHD symptoms with a twin heritability estimate of ADHD of 0.77 [36,40,69], more recent studies have examined environmental factors in susceptibility of this condition [70,71]. Consistent with this literature [60,61,63,[66][67][68][69][70][72][73][74][75][76], we observe that both severity of early ADHD symptoms and family socioeconomic background are important in differentiating those with varying probabilities of ADHD diagnosis in preschool. ...
Full-text available
We aimed to identify subgroups of young children with differential risks for ADHD, and cross-validate these subgroups with an independent sample of children. All children in Study 1 (N = 120) underwent psychological assessments and were diagnosed with ADHD before age 7. Latent class analysis (LCA) classified children into risk subgroups. Study 2 (N = 168) included an independent sample of children under age 7. A predictive model from Study 1 was applied to Study 2. The latent class analyses in Study 1 indicated preference of a 3-class solution (BIC = 3807.70, p < 0.001). Maternal education, income-to-needs ratio, and family history of psychopathology, defined class membership more strongly than child factors. An almost identical LCA structure from Study 1 was replicated in Study 2 (BIC = 5108.01, p < 0.001). Indices of sensitivity (0.913, 95% C.I. 0.814–0.964) and specificity (0.788, 95% C.I. 0.692–0.861) were high across studies. It is concluded that the classifications represent valid combinations of child, parent, and family characteristics that are predictive of ADHD in young children.
... One of the most reliable mediators of this risk is executive function. At 8 years, reduced performance on working memory and response inhibition tasks mediated the effect of institutional rearing on ADHD symptoms, but not on internalizing or externalizing problems (Tibu et al., 2016a). This effect was replicated for working memory at 12 years (Tibu et al., 2016b). ...
Over the last 20 years, we have learned much about the extent to which early‐life deprivation affects the mental health of children and adolescents. This body of evidence comes predominantly from studies of children raised in institutional care. The Bucharest Early Intervention Project (BEIP) is the only randomized controlled trial designed to evaluate whether the transition to family‐based foster care early in development can ameliorate the long‐term impact of institutional deprivation on psychopathology during vulnerable developmental windows such as adolescence. In this review, we detail the extent to which early deprivation affects mental health during this period, the capacity of family‐based care to facilitate recovery from early deprivation, and the mechanisms underpinning these effects spanning social–emotional, cognitive, stress, and neurobiological domains. We end by discussing the implications and directions for the BEIP and other studies of youth raised in institutions.
... Overall, the present results suggest that PS mediates the effect of low SES on psychological difficulties in PBTS, echoing evidence on the mediating role exerted by individual cognitive reserves on psychopathology in both healthy young individuals [106] and children facing early-childhood deprivation [120]. In more detail, PS was found to "fully" mediate the effect of a general proxy of psychological difficulties, including both internalizing and externalizing symptoms, as well as attention problems and hyperactivity. ...
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(1) Background: The relationship between processing speed (PS) and psychological adjustment in the healthy population is well established, as is that between low socio-economic status (SES) and psychological distress. While PS is one of the most impaired functions in pediatric brain tumor survivors (PBTSs), previous research has demonstrated that low SES may be a predictor of increased psychosocial risk in PBTSs. Given the psychological adjustment difficulties observed in PBTS, in the current study we aimed to explore the relationship between SES and psychological functioning, considering the contribution of PS as a mediator. (2) Methods: demographic and clinical data of 80 children (age range: 4–17 y.o.) were retrospectively collected. Psychological measures were the parent-compiled versions of the Child Behavioral Checklist (CBCL) and the Strengths and Difficulties Questionnaire (SDQ). Mediation analysis models were performed on psychological measures with and without the inclusion of covariates. (3) Results: The influence of SES on the CBCL total index was mediated by PS. Furthermore, PS was found to have a mediating effect on the relationship between SES and internalizing problems but not on the relationship between SES and externalizing problems. (4) Conclusions: The results suggest that PS may be a rehabilitation target for the prevention of psychological distress and should be addressed especially for PBTSs who live in a disadvantaged situation.
... Per the DMAP, reduced EF is a distinct neurodevelopmental mechanism linking deprivation with psychological functioning. In support of this claim, reductions in EF-specifically response inhibition and working memoryhave been shown to mediate the association between institutional deprivation and ADHD symptoms in childhood (ages 8 and 12 years) [105,106]. Moreover, children who experience less severe forms of deprivation, such as low SES, show increased rates of ADHD [107]. ...
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Emerging evidence suggests that partially distinct mechanisms may underlie the association between different dimensions of early life adversity (ELA) and psychopathology in children and adolescents. While there is minimal evidence that different types of ELA are associated with specific psychopathology outcomes, there are partially unique cognitive and socioemotional consequences of specific dimensions of ELA that increase transdiagnostic risk of mental health problems across the internalizing and externalizing spectra. The current review provides an overview of recent findings examining the cognitive (e.g., language, executive function), socioemotional (e.g., attention bias, emotion regulation), and mental health correlates of ELA along the dimensions of threat/harshness, deprivation, and unpredictability. We underscore similarities and differences in the mechanisms connecting different dimensions of ELA to particular mental health outcomes, and identify gaps and future directions that may help to clarify inconsistencies in the literature. This review focuses on childhood and adolescence, periods of exquisite neurobiological change and sensitivity to the environment. The utility of dimensional models of ELA in better understanding the mechanistic pathways towards the expression of psychopathology is discussed, with the review supporting the value of such models in better understanding the developmental sequelae associated with ELA. Integration of dimensional models of ELA with existing models focused on psychiatric classification and biobehavioral mechanisms may advance our understanding of the etiology, phenomenology, and treatment of mental health difficulties in children and youth.
... Threat exposure is linked with fear learning, attentional biases to negative emotional stimuli, heightened emotional reactivity, and deficits in automatic emotion regulation (Busso et al., 2017;McCrory et al., 2013;McLaughlin et al., 2015). Deprivation exposure is linked with decrements in language, executive function, and complex cognitive problem solving (Bos et al., 2009;Sheridan et al., 2017;Tibu et al., 2016). When examined simultaneously, threat selectively disrupts emotion reactivity and automatic regulation whereas deprivation selectively disrupts higher order cognitive function (Lambert et al., 2017;Miller et al., 2018;Sheridan et al., 2017). ...
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Background The association between adversity and psychopathology in adolescents and adults is characterized by equifinality. These associations, however, have not been assessed during early childhood when psychopathology first emerges. Defining adversity using both dimensional and cumulative risk approaches, we examined whether specific types of adversity are differentially associated with psychopathology in preschool‐aged children. Methods Measures of threat, deprivation, and total adversities (i.e., cumulative risk) were calculated based on parent‐reported information for 755 2‐ to 5‐year old children recruited from pediatric primary care clinics. Logistic regression was used to estimate cross‐sectional associations between type of adversity and anxiety, depression, ADHD, and behavioral disorder diagnoses. Results Threat and cumulative risk exhibited independent associations with psychopathology. Threat was strongly related to behavioral disorders. Cumulative risk was consistently related to all psychopathologies. Conclusions Using mutually adjusted models, we identified differential associations between threat and psychopathology outcomes in preschool‐aged children. This selectivity may reflect different pathways through which adversity increases the risk for psychopathology during this developmentally important period. As has been observed at other ages, a cumulative risk approach also effectively identified the cumulative impact of all forms of adversity on most forms of psychopathology during early childhood.
... These are contextual conditions characterized by reduced exposure to complex language, supervision by caregivers, and environmental stimulation Rosen et al., 2020;Rowe, 2008). In such deprived environments, children display difficulties in language and executive functioning (Bos et al., 2009;Lawson et al., 2018;Noble et al., 2007;Pollak et al., 2010;Spratt et al., 2012;Tibu et al., 2016;Windsor et al., 2011), reductions in cortical gray matter volume (Hodel et al., 2015;Noble et al., 2015;Simpson et al., 2012), thinner cortex throughout the brain and in the fronto-parietal network (McLaughlin, Sheridan, Winter et al., 2014;Rosen et al., 2018;Sheridan et al., 2017), and atypical patterns of fronto-parietal recruitment during executive functioning tasks (Rosen et al., 2018;Sheridan et al., 2017). Notably, the precise cellular mechanisms that lead to reductions in cortical gray matter following deprivation are currently unknown. ...
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Two extant frameworks – the harshness-unpredictability model and the threat-deprivation model – attempt to explain which dimensions of adversity have distinct influences on development. These models address, respectively, why, based on a history of natural selection, development operates the way it does across a range of environmental contexts, and how the neural mechanisms that underlie plasticity and learning in response to environmental experiences influence brain development. Building on these frameworks, we advance an integrated model of dimensions of environmental experience, focusing on threat-based forms of harshness, deprivation-based forms of harshness, and environmental unpredictability. This integrated model makes clear that the why and the how of development are inextricable and, together, essential to understanding which dimensions of the environment matter. Core integrative concepts include the directedness of learning, multiple levels of developmental adaptation to the environment, and tradeoffs between adaptive and maladaptive developmental responses to adversity. The integrated model proposes that proximal and distal cues to threat-based and deprivation-based forms of harshness, as well as unpredictability in those cues, calibrate development to both immediate rearing environments and broader ecological contexts, current and future. We highlight actionable directions for research needed to investigate the integrated model and advance understanding of dimensions of environmental experience.
Objective Differences in reward processing have been associated with numerous psychiatric disorders, including autism and ADHD. Many attempts to understand reward processing characterize differences in clinical populations after disorder onset; however, divergence may begin much earlier. In fact, the typical developmental progression of reward processing in infancy and early childhood is poorly understood. We reconceptualize classic infant developmental constructs such as preferential looking into a Six-Component Developmental Model of Reward Processing: an infant- and young child-focused framework to guide research and assessment of reward processing across development. Method The extant developmental literature including recent textbooks, systematic reviews, and meta-analyses was reviewed to build a conceptual framework. We describe experimental paradigms to assess each developmental component of reward processing longitudinally from infancy. A timeline of each component’s emergence was estimated. Results Six components of reward processing were identified — association, discrimination, preference/valuation, effort, anticipation, and response. Selected evidence suggests emergence between birth and six months. Application of this model to autism led to a reinterpretation of existing disparate results, and illuminated a path to study the developmental processes underlying a popular hypothesis of autism, the motivation hypothesis. Current evidence further suggests a sensitive period may exist for the emergence of reward processing. Conclusion The proposed framework offers a useful reconceptualization of the extant literature. Future longitudinal work using the suggested experimental paradigms with high-risk populations could elucidate the developmental trajectory of the six components and timing of potential sensitive period(s) for each component.
Hypotheses concerning the biologic embedding of early adversity via developmental neuroplasticity mechanisms have been proposed on the basis of experimental studies in animals. However, no studies have demonstrated a causal link between early adversity and neural development in humans. Here, we present evidence from a randomized controlled trial linking psychosocial deprivation in early childhood to changes in cortical development from childhood to adolescence using longitudinal data from the Bucharest Early Intervention Project. Changes in cortical structure due to randomization to foster care were most pronounced in the lateral and medial prefrontal cortex and in white matter tracts connecting the prefrontal and parietal cortex. Demonstrating the causal impact of exposure to deprivation on the development of neural structure highlights the importance of early placement into family-based care to mitigate lasting neurodevelopmental consequences associated with early-life deprivation.
Recent neurodevelopmental and evolutionary theories offer strong theoretical rationales and some empirical evidence to support the importance of specific dimensions of early adversity. However, studies have often been limited by omission of other adversity dimensions, singular outcomes, and short follow up durations. 1,420 participants in the community, Great Smoky Mountains Study, were assessed up to eight times between age 9 and 16 for four dimensions of early adversity: Threat, Material Deprivation, Unpredictability, and Loss (as well as a Cumulative Adversity measure). Participants were followed up to four times in adulthood (ages 19, 21, 25, and 30) to measure psychiatric disorders, substance disorder, and “real-world” functioning. Every childhood adversity dimension was associated with multiple adult psychiatric, substance, or functional outcomes when tested simultaneously in a multivariable analysis that accounted for other childhood adversities. There was evidence of differential impact of dimensions of adversity exposure on proximal outcomes (e.g., material deprivation and IQ) and even on distal outcomes (e.g., threat and emotional functioning). There were similar levels of prediction between the best set of individual adversity scales and a single cumulative adversity measure when considering distal outcomes. All dimensions of childhood adversity have lasting, pleiotropic effects, on adult health and functioning, but these dimensions may act via distinct proximal pathways.
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A Monte Carlo study compared 14 methods to test the statistical significance of the intervening variable effect. An intervening variable (mediator) transmits the effect of an independent variable to a dependent variable. The commonly used R. M. Baron and D. A. Kenny (1986) approach has low statistical power. Two methods based on the distribution of the product and 2 difference-in-coefficients methods have the most accurate Type I error rates and greatest statistical power except in 1 important case in which Type I error rates are too high. The best balance of Type I error and statistical power across all cases is the test of the joint significance of the two effects comprising the intervening variable effect.
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In this article, we attempt to distinguish between the properties of moderator and mediator variables at a number of levels. First, we seek to make theorists and researchers aware of the importance of not using the terms moderator and mediator interchangeably by carefully elaborating, both conceptually and strategically, the many ways in which moderators and mediators differ. We then go beyond this largely pedagogical function and delineate the conceptual and strategic implications of making use of such distinctions with regard to a wide range of phenomena, including control and stress, attitudes, and personality traits. We also provide a specific compendium of analytic procedures appropriate for making the most effective use of the moderator and mediator distinction, both separately and in terms of a broader causal system that includes both moderators and mediators. (46 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
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Early social deprivation can negatively affect domains of functioning. We examined psychopathology at age 12 years in a cohort of Romanian children who had been abandoned at birth and placed into institutional care, then assigned either to be placed in foster care or to care as usual. We used follow-up data from the Bucharest Early Intervention Project (BEIP), a randomised controlled trial of abandoned children in all six institutions for young children in Bucharest, Romania. In the initial trial, 136 children, enrolled between ages 6-31 months, were randomly assigned to either care as usual or placement in foster care. In this study we followed up these children at age 12 years to assess psychiatric symptoms using the Diagnostic Interview Schedule for Children (4th edition; DISC-IV). We also recruited Romanian children who had never been placed in an institution from paediatric clinics and schools in Bucharest as a comparator group who had never been placed in an institution. The primary outcome measure was symptom counts assessed through DISC-IV scores for three domains of psychopathology: internalising symptoms, externalising symptoms, and attention-deficit hyperactivity disorder (ADHD). We compared mean DISC-IV scores between trial participants and comparators who had never been placed in an institution, and those assigned to care as usual or foster care. Analyses were done by modified intention to treat. This trial is registered with, number NCT00747396. We followed up 110 children from the BEIP trial between Jan 27, 2011, and April 11, 2014, and 49 children as comparators who had never been placed in an institution. The 110 children who had ever been placed in an institution had higher symptom counts for internalising disorders (mean 0·93 [SD 1·68] vs 0·45 [0·84], difference 0·48 [95% CI 0·14-0·82]; p=0·0127), externalising disorders (2·31 [2·86] vs 0·65 [1·33], difference 1·66 [1·06-2·25]; p<0·0001), and ADHD (4·00 [5·01] vs 0·71 [1·85], difference 3·29 [95% CI 2·39-4·18]; p<0·0001) than did children who had never been placed in an institution. Compared with 55 children randomly assigned to receive care as usual, the 55 children in the foster-care group had fewer externalising symptoms (mean 2·89 [SD 3·00] for care as usual vs 1·73 [2·61] for foster care, difference 1·16 [95% CI 0·11 to 2·22]; p=0·0255), but symptom counts for internalising disorders (mean 1·00 [1·59] for care as usual vs 0·85 [1·78] for foster care, difference 0·15 [-0·35 to 0·65]; p=0·5681) and ADHD (mean 3·76 [4·61] for care as usual vs 4·24 [5·41] for foster care, difference -0·47 [-2·15 to 1·20; p=0·5790) did not differ. In further analyses, symptom scores substantially differed by stability of foster-care placement. Early foster care slightly reduced the risk of psychopathology in children who had been living in institutions, but long-term stability of foster-care placements is an important predictor of psychopathology in early adolescence. National Institute of Mental Health and the John D and Catherine T MacArthur Foundation. Copyright © 2015 Elsevier Ltd. All rights reserved.
Romania's Abandoned Children reveals the heartbreaking toll paid by children deprived of responsive care, stimulation, and human interaction. Compared with children in foster care, the institutionalized children in this rigorous twelve‐year study showed severe impairment in IQ and brain development, along with social and emotional disorders.
Attention deficit hyperactivity disorder (ADHD) is widely theorized to stem from dysfunctional inhibitory processes. However, the definition of inhibition is imprecisely distinguished across theories. To clarify the evidence for this conception, the author relies on a heuristic distinction between inhibition that is under executive control and inhibition that is under motivational control (anxiety or fear). It is argued that ADHD is unlikely to be due to a motivational inhibitory control deficit, although suggestions are made for additional studies that could overturn that conclusion. Evidence for a deficit in an executive motor inhibition process for the ADHD combined type is more compelling but is not equally strong for all forms of executive inhibitory control. Remaining issues include specificity to ADHD, whether inhibitory problems are primary or secondary in causing ADHD, role of comorbid anxiety and conduct disorder, and functional deficits in the inattentive ADHD subtype.
Objective: Despite growing interest in adult attention deficit hyperactivity disorder (ADHD), little is known about its prevalence or correlates. Method: A screen for adult ADHD was included in a probability subsample (N=3,199) of 18-44-year-old respondents in the National Comorbidity Survey Replication, a nationally representative household survey that used a lay-administered diagnostic interview to assess a wide range of DSM-IV disorders. Blinded clinical follow-up interviews of adult ADHD were carried out with 154 respondents, oversampling those with positive screen results. Multiple imputation was used to estimate prevalence and correlates of clinician-assessed adult ADHD. Results: The estimated prevalence of current adult ADHD was 4.4%. Significant correlates included being male, previously married, unemployed, and non-Hispanic white. Adult ADHD was highly comorbid with many other DSM-IV disorders assessed in the survey and was associated with substantial role impairment. The majority of cases were untreated, although many individuals had obtained treatment for other comorbid mental and substance-related disorders. Conclusions: Efforts are needed to increase the detection and treatment of adult ADHD. Research is needed to determine whether effective treatment would reduce the onset, persistence, and severity of disorders that co-occur with adult ADHD.
Background: This study investigated whether familyenvironment risk factors are associated with attentiondeficit hyperactivity disorder (ADHD). Compelling work by Rutter and coworkers revealed that it was the aggregate of adversity factors (severe marital discord, low social class, large family size, paternal criminality, maternal mental disorder, and foster care placement) rather than the presence of any single factor that led to impaired development. Based on the work of Rutter, we hypothesized a positive association between indicators of adversity and the diagnosis of ADHD and ADHD-associated impairments.Methods: We studied 140 ADHD and 120 normal control probands. Subjects were non-Hispanic white boys between the ages of 6 and 17 years. Rutter's indicators of adversity were used to predict ADHD-related psychopathology as well as impaired cognitive and psychosocial functioning.Results: The odds ratio for the diagnosis of ADHD increased as the number of Rutter's adversity indicators increased. Higher scores on Rutter's adversity index predicted ADHD-related psychopathology (depression, anxiety, and conduct disorder), learning disabilities, cognitive impairment, and psychosocial dysfunction.Conclusions: A positive association appears to exist between adversity indicators and the risk for ADHD as well as for its associated psychiatric, cognitive, and psychosocial impairments. These findings support the work of Rutter and stress the importance of adverse family-environment variables as risk factors for children with ADHD.