Disruptions of working memory and inhibition
mediate the association between exposure to
institutionalization and symptoms of attention deﬁcit
*, 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 Children’s 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
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 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.
Deﬁcits in working memory and response inhibition were speciﬁc mechanisms leading to ADHD in previously institu-
tionalized children. These ﬁndings 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 deﬁcits 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 deﬁcit 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-speciﬁc 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) deﬁcits 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 reﬂects as yet unidentiﬁed 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
deﬁcits 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 deﬁcits 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-
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). Deﬁcits 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 ﬁnd links between the children’s
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 6–31 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 ﬂowchart 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 signiﬁcant
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://
www.cantab.com), 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 difﬁculty increases with the number of pat-
terns contained in the boxes. Outcome variables
include stages completed at ﬁrst trial, total stages com-
pleted, and memory score (i.e. number of patterns cor-
rectly located after the ﬁrst trial summed across the
Spatial Working Memory (SWM) tests the ability to
retain spatial information across a delay and to ma-
nipulate remembered items in working memory. A
Deﬁcits in EF and the link between institutionalization and ADHD 3
number of 3–8 colored boxes are shown on the screen
and the subject is invited, by process of elimination, to
ﬁnd a blue token in each of these boxes and use it to ﬁll
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= 56) Group difference
Age at testing,
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
EIG, Ever institutionalized group; NIG, never institutiona-
lized group; N.S., not signiﬁcant.
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 difﬁculty of the trials increases gradually
from two-move problems to more complex models that
require ﬁve moves to solve. Key outcomes are number
of trials solved in minimum moves, mean number of
moves for each level of difﬁculty, and initial and sub-
sequent thinking times.
The Flanker task assesses the children’s capacity to
respond to target stimuli in the context of other dis-
tracting stimuli. A series of ﬁve 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 ﬂanked
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
reﬂect 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.
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 ﬁnal 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 signiﬁcantly,
a signiﬁcant 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 signiﬁcance
of the mediator using a bootstrapping approach that
provides bias corrected conﬁdence intervals and
allows multiple mediators (i.e. measures of EF) to be
examined in one model (Preacher & Hayes, 2008).
Conﬁdence intervals that do not include zero indicate
signiﬁcant mediation. Age and gender were included
as covariates in all analyses, and statistical signiﬁcance
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 signiﬁcantly 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 ﬁve tasks. Results are presented in Table 3 and
show that children in the EIG performed signiﬁcantly
more poorly than NIG children on multiple
Deﬁcits 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 signiﬁcantly
lower accuracy on the longest delay trials of the DMS
= 10.89, p= 0.001), a lower number of PAL
stages completed on ﬁrst trial (F
= 7.78, p= 0.006),
lower PAL ﬁrst trial memory scores (F
p= 0.001), lower SWM strategy scores (F
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).
ADHD and EF
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 signiﬁcantly
associated with several aspects of working memory
performance. These included the number of PAL
stages completed on ﬁrst trial, PAL ﬁrst 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 ﬁndings with inattention symptoms,
we observed signiﬁcant associations between impulsiv-
ity and PAL ﬁrst trial memory score, SWM strategy
score, SWM between errors and a marginally signiﬁ-
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 ﬁrst trial.
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 signiﬁcant (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
ﬁrst trial, PAL ﬁrst 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 signiﬁcant [95% conﬁdence 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 signiﬁcant (95% CIs −0.28 to 0.00;
−0.19 to 0.03 respectively).
Similarly, the total effect of institutionalization in
predicting impulsivity was signiﬁcant (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 signiﬁcant (95% CI −0.80 to −0.04).
Likewise, the total effect of institutionalization on
impulsivity was signiﬁcant (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 signiﬁ-
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 signiﬁcant (95% CI −0.40
to 0.01). Together, these ﬁndings suggest that inatten-
tion and impulsivity associated with exposure to insti-
tutionalization are partially explained by deﬁcits in
working memory and response inhibition, but not
Speciﬁcity of associations
In order to ascertain that deﬁcits in EF represent a
mechanism which speciﬁcally 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 deﬁcit hyperactivity disorder; EIG, ever
institutionalized group; NIG, never institutionalized group.
*Signiﬁcant 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/deﬁant 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 deﬁcits are a pathway linked
speciﬁcally to ADHD symptoms.
The purpose of the current study was to test whether
deﬁcits 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 deﬁcits
in working memory (for both inattention and impul-
sivity) and response inhibition (for impulsivity only),
but was not accounted for by planning ability. These
ﬁndings build on previous reports describing the path-
ways through which institutionalization inﬂuences
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;
*Signiﬁcant 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
DMS % accuracy 12 000 ms
−0.17 0.059 −0.16 0.07
PAL stages completed on
−0.24 0.004 −0.11 0.16
PAL ﬁrst 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
Flanker RT incongruent –
−0.21 0.012 −0.24 0.004
SOC problems solved in
−0.15 0.079 −0.19 0.018
ADHD, Attention deﬁcit 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.
Deﬁcits 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
deﬁcits 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 ﬁrst 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 signiﬁcance. Here, we found that re-
sponse inhibition served as a signiﬁcant mediator of
the association between institutionalization and impul-
sivity, a speciﬁc cluster of ADHD symptomatology.
Previous investigations in the BEIP and other sam-
ples of children adopted from Eastern Europe have
identiﬁed 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 ﬁndings, the current paper
explores the mediating pathway of speciﬁccognitive
functions, namely working memory, response inhib-
ition, and planning. Our ﬁndings point to speciﬁc cog-
nitive functions that link institutionalization to ADHD,
but not common to other forms of externalizing psy-
chopathology or to internalizing psychopathology.
We also ﬁnd speciﬁcity in the speciﬁc domains of EF
that are involved in this association. Two ﬁndings are
Fig. 2. Model of the association between institutionalization and symptoms of inattention at 8 years as mediated by indices of
. ADHD, attention-deﬁcit/hyperactivity disorder. [
Unstandardized coefﬁcients 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 deﬁcit hyperactivity disorder.
Unstandardized coefﬁcients 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
deﬁcits in working memory only during the most difﬁ-
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 ﬁnding that the
association between institutional rearing and ADHD
was mediated speciﬁcally 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 speciﬁc 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 speciﬁc mental health outcomes,
including ADHD. Our ﬁndings suggest that although
children exposed to institutional rearing exhibit deﬁcits
in multiple forms of EF, the association with ADHD
symptoms is explained primarily by deﬁcits in work-
ing memory and response inhibition. Given the sample
size, and the fact that our main effect differs subtly
from previous ﬁndings, 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-signiﬁcant mediating effect of
planning needs to be replicated in future investigations
before ﬁrm conclusions are drawn.
These ﬁndings 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 ﬁnding 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 ﬁnding 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 proﬁle of children who have
ADHD following exposure to institutionalization is
very similar to the proﬁles 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 ﬁndings
are based on EF and ADHD data collected at the same
point in development, this ﬁrst point that EF was
assessed in the study. This suggests that our ﬁndings
could also reﬂect 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 reﬂect more
adequately the manifestations of the problem. Finally,
we were not able to account for the possible inﬂuence
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 identiﬁed 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
Deﬁcits in EF and the link between institutionalization and ADHD 9
psychosocial deprivation in orphanages in Romania.
The current ﬁndings 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. Speciﬁcally, our ﬁndings suggest that inter-
ventions designed to improve working memory and
inhibition (Klingberg et al. 2005; Johnstone et al. 2010)
could have a beneﬁcial 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 uniﬁed theory of
ADHD. Psychological Bulletin 121,65–94.
Barkley RA (2001). The inattentive type of ADHD as a
distinct disorder: what remains to be done. Clinical
Psychology: Science and Practice 8, 489–493.
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, 1173–1182.
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-deﬁcit
hyperactivity disorder. A test of Rutter’s indicators of
adversity. Archives of General Psychiatry 52, 464–470.
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
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, 163–171.
Coghill DR, Hayward D, Rhodes SM, Grimmer C,
Matthews K (2014). A longitudinal examination of
neuropsychological and clinical functioning in boys with
attention deﬁcit 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 deﬁcits
underlie the adverse outcomes associated with profound
early deprivation? Findings from the ERA study. Journal of
Abnormal Child Psychology 36, 1057–1068.
DePrince AP, Weinzierl KM, Combs MD (2009). Executive
function performance and trauma exposure in a community
sample of children. Child Abuse and Neglect 33, 353–361.
Eriksen CW, Schultz DW (1979). Information processing in
visual search: a continuous ﬂow conception and
experimental results. Perception & Psychophysics 25, 249–263.
Essex MJ, Boyce WT, Goldstein LH, Armstrong JM,
Kraemer HC, Kupfer DJ (2002). The conﬂuence of mental,
physical, social, and academic difﬁculties in middle
childhood. II. Developing the MacArthur health and
behavior questionnaire. Journal of the American Academy of
Child and Adolescent Psychiatry 41, 588–603.
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 efﬁciency 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, 468–475.
Halperin JM, Schulz KP (2006). Revisiting the role of the
prefrontal cortex in the pathophysiology of attention-
deﬁcit/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, 17208–17212.
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, 625–634.
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
Deﬁcit Hyperactivity Disorders 2,31–42.
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, 716–723.
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, 177–186.
Kreppner JM, O’Connor TG, Rutter M,English &
Romanian Adoptees (ERA) Study Team (2001). Can
inattention/overactivity be an institutional deprivation
syndrome? Journal of Abnormal Child Psychology 29, 513–528.
Lemery‐Chalfant 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 54,37–45.
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, 595–624.
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 7,83–104.
Martel M, Nikolas M, Nigg JT (2007). Executive function in
adolescents with ADHD. Journal of the American Academy of
Child and Adolescent Psychiatry 46, 1437–1444.
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, 377–384.
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-deﬁcit/hyperactivity disorder. Biological Psychiatry
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-deﬁcit/
hyperactivity disorder. Biological Psychiatry 76, 629–638.
Merz EC, McCall RB (2011). Parent ratings of executive
functioning in children adopted from psychosocially
depriving institutions. Journal of Child Psychology and
Psychiatry 52, 537–546.
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, 726–733.
Nelson CA, Fox NA, Zeanah CH (2014). Romania’s 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, 241–268.
Nigg JT (2001). Is ADHD a disinhibitory disorder?
Psychological Bulletin 127, 571–598.
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, 767–786.
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, 1550–1564.
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, O’Connor TG,The English
Romanian Adoptees (ERA) Study Team (2001). Speciﬁcity
and heterogeneity in children’s 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-speciﬁc psychological patterns: effects of
institutional deprivation. Monographs of the Society for
Research in Child Development 75,1–242.
Schoemaker K, Bunte T, Wiebe SA, Espy KA, Dekovic M,
Matthys W (2012). Executive function deﬁcits in preschool
children with ADHD and DBD. Journal of Child Psychology
and Psychiatry 53, 111–119.
Deﬁcits in EF and the link between institutionalization and ADHD 11
Sergeant J (2000). The cognitive-energetic model: an empirical
approach to attention-deﬁcit hyperactivity disorder.
Neuroscience and Biobehavioral Reviews 24,7–12.
Shallice T (1982). Speciﬁc 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
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, 255–272.
Spencer TJ, Biederman J, Mick E (2007). Attention-deﬁcit/
hyperactivity disorder: diagnosis, lifespan, comorbidities,
and neurobiology. Journal of Pediatric Psychology 32,631–642.
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, 451–467.
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-deﬁcit/hyperactivity disorder: a meta-analytic
review. Biological Psychiatry 57, 1336–1346.
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, 777–785.
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
12 000 ms
on ﬁrst trial
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
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
1 0.79*** −0.03 −0.32*** −0.02 0.19*
PAL ﬁrst trial memory
1−0.08 −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
SOC problems solved in
DMS, Delayed Matching to Sample; PAL, Paired Associates Learning; SWM, Spatial Working Memory; RT, reaction time; SOC, Stockings of Cambridge.
* Correlation is signiﬁcant at the 0.05 level (two-tailed).
** Correlation is signiﬁcant at the 0.01 level (two-tailed).
*** Correlation is signiﬁcant at the 0.001 level (two-tailed).
Deﬁcits in EF and the link between institutionalization and ADHD 13