mildly stressful separation and are used to classify infants as either
securely or insecurely attached. Securely attached infants tend to
readily greet or approach their caregivers; they accept comfort
and calm quickly. In contrast, insecurely attached infants either
ignore their caregivers or alternately approach and reject them;
such infants are slow to calm.
Research on the precursors of infant attachment suggests a role
for both environmental and genetic factors. Regarding environ-
mental factors, traditional methods of mother–infant observation
have consistently identified parenting behaviors as modest, though
robust, sources of variance in the quality of infant attachment. For
example, maternal sensitivity and responsiveness has been associated
with infant security; similarly, maternal inconsistency, and rejec-
tion have been found to be related to infant insecurity (Ainsworth
et al., 1978; de Wolff and van Ijzendoorn, 1997). Regarding genetic
factors, some behavioral genetic studies on twins suggest that
infant attachment also has a heritable component, although other
studies have disputed this (see Bakermans-Kranenburg and van
IJzendoorn, 2007, for a review of this literature).
Recent advances in molecular genetics permit a different, prom-
ising, approach to the examination of genetic influences on attach-
ment by focusing on specific candidate genes. Polymorphisms in
genes involved in the production, transport, and metabolism of
many neurotransmitters and brain substances have now been
related to a variety of mental health outcomes, including psy-
chiatric conditions (Caspi and Moffitt, 2006; Psychiatric GWAS
Consortium Coordinating Committee, 2009), as well as to normal
variations in stress reactivity (Gotlib et al., 2008) and shyness and
behavioral inhibition (Fox et al., 2005). Indeed, several investigators
OxytOcin ReceptOR (OXTR) pOlymORphisms pRedict
AttAchment in humAn infAnts
Humans are social creatures, though some more than others. Even
in infancy, humans vary dramatically in their proclivity to seek
and accept comfort from caregivers (Bowlby, 1969/1982; Ainsworth
et al., 1978). These ordinary variations, readily observable in infancy,
are associated with a wide range of individual differences in psycho-
logical functioning in adults. Infants who rely on their caregivers
with ease and confidence, compared with infants who do not, are
more likely to experience stronger cognitive and language develop-
ment (van IJzendoorn et al., 1995; Sroufe et al., 2005), healthier
interpersonal relations (Sroufe et al., 2005), and decreased risk of
later mental health problems such as mood disorders, externalizing
disorders, and dissociative and attentional disorders (Warren et al.,
1997; Carlson, 1998; Greenberg, 1999; Clarke et al., 2002; Sroufe
et al., 2005). Although scientists have devoted considerable effort
to identifying the foundations of these differences, much remains
unknown. In this article we present evidence from molecular genet-
ics demonstrating that at least some of the variance in the quality
of infants’ attachment behavior is associated with a polymorphism
of the oxytocin receptor gene (OXTR).
Attachment is a theory of social stress-regulation, concerned
specifically with how infants use caregivers to modulate their own
stress. Systematic individual differences in infants’ use of caregivers
are posited to correspond to infants’ expectations and trust of car-
egivers (Bowlby, 1969/1982; Ainsworth et al., 1978; Johnson et al.,
2007). In the standard method for assessing individual differences,
known as the Strange Situation (Ainsworth et al., 1978), infants’
parent-directed behaviors are observed immediately following a
Oxytocin receptor (OXTR) polymorphisms and attachment in
Frances S. Chen1*, Maria E. Barth2, Stephen L. Johnson3, Ian H. Gotlib4 and Susan C. Johnson5*
1 Department of Psychology, University of Freiburg, Freiburg, Germany
2 Department of Psychology, Tufts University, Boston, MA, USA
3 Department of Genetics, Washington University Medical School, St. Louis, MO, USA
4 Department of Psychology, Stanford University, Stanford, CA, USA
5 Department of Psychology, Ohio State University, Columbus, OH, USA
Ordinary variations in human infants’ attachment behaviors – their proclivity to seek and
accept comfort from caregivers – are associated with a wide range of individual differences in
psychological functioning in adults. The current investigation examined variation in the oxytocin
receptor (OXTR) gene as one possible source of these variations in infant attachment. One
hundred seventy-six infants (77 Caucasian, 99 non-Caucasian) were classified as securely or
insecurely attached based on their behavior in the Strange Situation (Ainsworth et al., 1978).
The A allele of OXTR rs2254298 was associated with attachment security in the non-Caucasian
infants (p < 0.005). These findings underscore the importance of oxytocin in the development
of human social behavior and support its role in social stress-regulation and the development
Keywords: attachment, trust, development, oxytocin, polymorphisms
Daniel Richardson, University College
Angelica Ronald, Birkbeck College, UK
Emma Meaburn, Birkbeck, University
of London, UK
Frances S. Chen, Department of
Psychology, University of Freiburg,
Stefan-Meier-Strasse 8, D-79104
Susan S. Johnson, Department of
Psychology, The Ohio State University,
Columbus, OH 614-292-8964, USA.
www.frontiersin.org August 2011 | Volume 2 | Article 200 | 1
Original research article
published: 25 August 2011
have found associations between attachment-relevant behavior and
polymorphisms involved in the dopamine and serotonin systems
in both adults (Gillath et al., 2008; van IJzendoorn et al., 2008)
and children (Bakermans-Kranenburg and van IJzendoorn, 2007;
Gervai et al., 2007; Barry et al., 2008), consistent with the role of
these neurotransmitters in the regulation of social stress-regulation
and approach/withdrawal behaviors.
Another promising target of inquiry is oxytocin and its recep-
tors. Oxytocin is a neuropeptide produced in the hypothalamus
and projected via axon transmission into the amygdala and its
associated areas where the oxytocin receptor is found (Insel, 1997;
Winslow and Insel, 2002). In animals, oxytocin has been found to
influence a host of mammalian social behaviors including mother–
infant attachment, pair bonding, social recognition, and social com-
munication (Insel, 1997; Winslow and Insel, 2002; Takayanagi et al.,
2005; Lim and Young, 2006). Indeed, both oxytocin and oxytocin
receptor knockout mice show severe deficits in social behavior
(Winslow and Insel, 2002; Takayanagi et al., 2005).
Oxytocin also plays an important role in the social behavior of
humans. A single dose of intranasally administered oxytocin has
been found to increase healthy adults’ attention to the eye region
of faces (Guastella et al., 2007), to enhance their ability to infer
mental states from eye-related information (Domes et al., 2007),
to strengthen their memory for emotional faces (Savaskan et al.,
2008), to dampen their negative reactions to aversive faces (Kirsch
et al., 2005; Petrovic et al., 2008), and to facilitate their recogni-
tion of positive social words (Unkelbach et al., 2008). The effects
of oxytocin appear to be specific to social stimuli: compared to
controls, adults who received a dose of oxytocin-laden nasal spray
accepted greater risk from unseen human partners and trusted
them with more of their own money than they did unseen inter-
active computers (Kosfeld et al., 2005). Finally, Buchheim et al.
(2009) reported that the intranasal administration of oxytocin
increased the experience of attachment-related security in previ-
ously insecure adults.
Oxytocin has also been studied in the context of atypical devel-
opment. Pollak and his colleagues, for example, found that children
with a history of institutionalization and social deprivation showed
a smaller rise in urinary oxytocin during an interactive episode with
their caregivers than did children without such a history (Wismer
Fries et al., 2005). Investigators have also found that intravenous
administration of oxytocin improves the social cognition of patients
with autism, a neurodevelopmental disorder characterized in part
by a lack of social engagement (Hollander et al., 2007).
Polymorphisms exist in the genes for both oxytocin and its
receptor. Motivated in part by recent work documenting asso-
ciations between autism and polymorphisms at several loca-
tions within the oxytocin receptor gene (Wu et al., 2005; Jacob
et al., 2007; Lerer et al., 2007; Liu et al., 2010), recent studies have
examined associations between attachment-related phenomena in
adults and single nucleotide polymorphisms (SNPs) within OXTR.
The A allele of OXTR rs53576 has been linked to less sensitive
parenting behavior (Bakermans-Kranenberg and van Ijzendoorn,
2008), higher stress reactivity (Rodrigues et al., 2009), reduced
social support seeking (Kim et al., 2010), and reduced amygdala
activation when processing facial emotions (Tost et al., 2010). In
one study, the G allele of rs53576 was associated with insecure
attachment in depressed adults (Costa et al., 2009); however, two
studies found no association between rs53576 and adults’ reports
of their own attachment (Gillath et al., 2008; Rodrigues et al.,
2009). Another common polymorphism in OXTR, rs2254298, has
been linked to amygdala volume in both adults (Inoue et al., 2010)
and adolescent girls (Furman et al., 2011), attachment anxiety
in adult females and autism-spectrum traits in males (Chen and
Johnson, 2011), and depression and anxiety symptoms in adoles-
cent girls (Thompson et al., 2011). However, inconsistent patterns
of association between particular alleles (A vs. G) and specific
phenotypic outcomes have been reported for rs2254298 (cf. Wu
et al., 2005; Jacob et al., 2007).
Considered collectively, the results from animal work, healthy
adults, and atypically developing children all point to a probable
role of oxytocin in the social development and attachment-
related behaviors of healthy infants. Although it is not feasible
to extract samples of oxytocin from, or administer oxytocin
to, healthy infants, the tools of molecular genetics are readily
applied to this population. In this context, the goal of the cur-
rent study was to examine associations between allelic variants
at two loci of the oxytocin receptor gene and infant attachment
behavior, while taking into consideration possible population
mAteRiAls And methOds
Data were obtained from 176 healthy infants (98 male) between the
ages of 12 and 16 months recruited from a larger study of infant
social development in San Francisco Bay Area. Two tested infants
for whom DNA extraction failed were not included in the sample.
The sample included 77 Caucasians and 99 non-Caucasians. Of
the 132 parents who reported family income levels, 46 earned less
than the regional median of approximately $100,000 annually for
a family of 4, and 86 families earned more. Of the 160 primary
caregivers who reported their highest attained educational level, 22
had a high school degree or some college, 80 had a college degree,
and 58 had a graduate degree.
Parents reported the child’s ethnicity and race using the catego-
ries developed by the National Institute of Health for reporting
purposes. These include two ethnic categories (Hispanic or Latino,
and Not Hispanic or Latino) and five racial categories (American
Indian or Alaska Native, Asian, Black or African American, Native
Hawaiian or Other Pacific Islander, and White). For our purposes,
infants reported to be Non-Hispanic and White were classified as
“Caucasian,” and all others as “non-Caucasian.” Because the allele
frequencies in Caucasian populations that have been studied to
date differ significantly from those documented in all other popu-
lations studied to date1, analyses combining data from Caucasian
and non-Caucasian infants introduce the potential confound of
population stratification due to genetic drift. Thus, we also included
ethnicity (Caucasian and non-Caucasian) in our analyses. Although
“non-Caucasian” does not designate a genetically homogenous
population, very similar allele frequencies at rs2254298 have been
documented in the three non-Caucasian populations that have
been studied to date (see text footnote 1).
Chen et al. OXTR and attachment in humans
Frontiers in Psychology | Developmental Psychology
August 2011 | Volume 2 | Article 200 | 2
in the human genome database (see text footnote 1), Jacob et al.
(2007), and Wu et al. (2005). For both SNPs, the A allele was more
common in the non-Caucasian samples than in the Caucasian
samples. To test for association between the two SNPs, we used
Haploview 4.23 to calculate r2, a measure of linkage disequilib-
rium. In our overall sample as well as within the two ethnic
subsamples, negligible linkage disequilibrium was observed (all
r2 < 0.01).
For rs53576, preliminary analyses using an additive genetic
model revealed no significant effects. Therefore, a dominant genetic
model (grouping infants based on the presence or absence of at
least one A allele) was also tested; this model has also been used in
previous studies showing associations between rs53576 and social
behavior in humans (Bakermans-Kranenberg and van Ijzendoorn,
2008; Rodrigues et al., 2009). For rs2254298, testing the additive
genetic model would have been uninformative given the rarity of
the AA carriers – only five AA carriers (3%) were present in the
sample. Therefore, we used a dominant genetic model, combining
the AA and AG carriers creating into a single group defined by hav-
ing at least one A allele. Eliminating the AA carriers entirely from
the analyses to leaving a comparison of only AG vs. GG carriers
(the strategy taken in Thompson et al., 2011) does not significantly
change any of the reported results.
A dominant genetic model was tested, with infants grouped
according to the presence (n = 103) or absence (n = 73) of at
least one A allele. Consistent with the previous finding in adults
of Gillath et al. (2008), we found no association between variants
of rs53576 and security of attachment, even when accounting for
ethnicity and sex, as tested by a logistic regression with the terms
entered together: rs53576 (presence vs. absence of the A allele),
ethnicity (Caucasian vs. non-Caucasian), sex, and their interac-
tions, all ps > 0.45.
Grouping the infants according to the presence of at least one A
allele resulted in 47 infants with and 129 without. As with other
findings in the literature (Wu et al., 2005; Jacob et al., 2007), the
association between the genotype at rs2254298 (presence vs.
All parents gave their written informed consent. The study was
approved by the Institutional Review Board of Stanford University.
All statistical analyses were conducted using SPSS18 (SPSS, Inc.).
The quality of each infant’s attachment to his/her primary caregiver
was assessed using the Strange Situation, a standardized procedure
and set of coding criteria developed by Ainsworth et al. (1978). This
procedure guides the infant through a series of 3 min episodes in
which he or she is first brought, with his or her caregiver, to an
unfamiliar room filled with toys, then introduced to a stranger,
left alone with the stranger, and finally left entirely alone. After
each separation the infant is reunited with either the stranger or
his or her caregiver. Infants’ approach, physical contact, resistant,
and avoidant behaviors toward the caregiver in reunion episodes
were used to classify infants as either secure or insecure (Ainsworth
et al., 1978). The primary coder was trained and certified at the
Minnesota Institute for Child Development Attachment Workshop.
A secondary coder double-coded 85 (48%) of the tapes, κ = 0.70.
Two SNPs were selected for genotyping on the basis of their known
association with autism as well as with attachment-related out-
comes in healthy adults: OXTR rs2254298 and OXTR rs53576. Both
are located in the third intron of OXTR and are likely non-coding
markers of unidentified functional variations in the oxytocin recep-
DNA was collected from saliva samples using the
Oragene Kit (DNA Genotek,
Amplification of rs2254298 was performed with the prim-
antisense primer 5′-AACGCCCACCCCAGTTTCTTC-3′
under standard conditions. Amplification of rs53576 was per-
formed with the primers GCCCACCATGCTCTCCACATC and
GCTGGACTCAGGAGGAATAGGGAC. Call rates were ∼98% for
each SNP. Three samples that failed on the first attempt were suc-
cessfully re-run. Genotyping was carried out by KBiosciences using
their internal KASP chemistry, a form of fluorescence-based com-
petitive allele-specific PCR using FRET quencher cassette oligonu-
cleotides. Further details of the assay design are available directly
Ottawa, ON, Canada).
Ninety-eight of the infants (56%) were classified as secure and
78 (44%) as insecure. Preliminary analyses yielded no effects of
family income or caregiver’s education on the rate of security;
consequently, these variables were removed from further analysis.
Allele and genotype frequencies of both SNPs are summarized
in Table 1. Both SNPs were in Hardy–Weinberg equilibrium for
the overall sample as well as the Caucasian and non-Caucasian
subsamples (all ps > 0.47). The allele frequencies in our Caucasian
and non-Caucasian samples are consistent with those reported
Table 1 | Allele and genotype frequencies of OXTR SNPs.
Allele distribution Genotype distribution
G A GG AG AA
Non-Caucasians 110 (56%) 88 (44%)
Overall sample 300 (85%) 52 (15%)
Caucasians 141 (92%) 13 (8%)
Non-Caucasians 159 (80%) 39 (20%)
224 (64%) 128 (36%) 73 (41%)
114 (74%) 40 (26%)
78 (44%) 25 (14%)
32 (42%) 4 (5%)
46 (46%) 21 (21%)
129 (73%) 42 (24%) 5 (3%)
65 (84%) 11 (14%)
64 (65%) 31 (31%) 4 (4%)
Chen et al. OXTR and attachment in humans
www.frontiersin.org August 2011 | Volume 2 | Article 200 | 3
if they had the A allele at rs2254298 than if they did not, p = 0.003
by a logistic regression (see Table 2). Given our sample size and
observed effect size, the power to detect a significant (at the 5%
level) main effect of rs2254298 (dominant model) on attachment
status in non-Caucasians was 65%.
These results are the first to document a specific association
between a polymorphism in the oxytocin receptor gene and indi-
vidual differences in the security of attachment in a population
of human infants. The association suggests that there are at least
two functional variants of the oxytocin receptor gene. The variant
marked by the A allele at rs2254298 was significantly more likely to
be associated with secure attachment than was the variant marked
by the G allele in non-Caucasian infants, but not in Caucasian
infants. These non-Caucasian infants were more willing and able to
accept comfort from their caregivers if they had at least one A allele
at rs2254298 than if they did not. As a group, Caucasian infants
showed no associations between the rs2254298 SNP and security
of attachment. No associations were found with the rs53576 SNP
in any ethnic group.
It is not clear why there was not a significant association between
OXTR and attachment in the Caucasian infants. It is noteworthy,
however, that previous studies have documented ethnic differ-
ences in OXTR associations with phenotype. In the Chinese Han
population studied by Wu et al. (2005), the A allele of rs2254298
was associated with autism. In contrast, in the Caucasian sam-
ple studied by Jacob et al. (2007), the G allele was associated with
autism. One explanation for this discrepancy involves patterns of
linkage disequilibrium between the functional loci and the associ-
ated markers used in these studies. In evolutionary time, patterns
of linkage disequilibrium naturally change through the recurring
process of recombination. When two populations diverge, the pat-
terns of linkage disequilibrium within each may also diverge. It is
possible, therefore, that a functional SNP of OXTR is linked to the
rs2254298 A allele in the Chinese Han population, but the G allele in
the Caucasian population. These patterns of linkage disequilibrium
would be consistent with the observation that Caucasian infants are
not less likely to be securely attached than non-Caucasian infants
despite the relatively low frequency of the A allele in Caucasian
populations (see text footnote 1).
Even without differences in patterns of linkage disequilibrium,
possible interactions with other genetic or cultural factors may
affect our ability to detect oxytocin receptor function in some popu-
lations more than in others. For instance, an important role of
oxytocin receptors is to regulate serotonin (Yoshida et al., 2009) and
dopamine function (Liu and Wang, 2003). Serotonin and dopamine
function, however, are influenced by multiple factors, including
absence of the A allele) and the behavioral outcome (secure vs.
insecure) appeared to differ as a function of ethnicity (Caucasian
vs. non-Caucasian), with the opposite directions of association in
the two groups (Figure 1). This interaction was confirmed with
a logistic regression in which genotype, ethnicity, sex, and their
possible interactions were entered together, which remains signifi-
cant (p < 0.05) after accounting for multiple testing of two SNPs
(rs53576 and rs2254298) using a Bonferroni correction.
To examine the association between rs2254298 and security of
attachment further, we conducted further separate regression analy-
ses on each population. Because no effects for sex were seen, it was
removed from these further analyses. We also performed post hoc
power estimations for the logistic regression analyses of both the
Caucasian and non-Caucasian samples using the power calculator
for logistic regressions at http://www.dartmouth.edu/∼eugened/
OXTR Rs2254298 AnAlysis by ethnicity
Six of the 12 Caucasian infants (50%) with the A allele and 39 of
the 65 Caucasian infants (60%) without the A allele were securely
attached to their caregivers. A logistic regression detected no asso-
ciation between the presence of an A allele at rs2254298 and the
attachment status of the Caucasian infants, p > 0.50 (see Table 2).
Given our sample size and observed effect size, the power to detect
a significant (at the 5% level) main effect of rs2254298 (dominant
model) on attachment status in Caucasians was less than 1%.
In contrast to the Caucasians, 26 of the 35 non-Caucasians infants
(74%) with the A allele were securely attached compared to only 27
of the 64 infants (42%) without it. Thus, the non-Caucasian infants
were almost four times more likely to develop a secure attachment
Table 2 | Logistic regressions predicting security of attachment from
presence or absence of the A allele at OXTR rs2254298 for Caucasian
and non-Caucasian populations.
Population B Wald χ2
p Odds ratio [95% CI]
0.67 [0.19, 2.29]
3.95 [1.60, 9.80]
FIGuRe 1 | Percentage of infants classified as secure as a function of
rs2254298 genotype and ethnicity. Group A includes infants with the AA or
AG genotype. Group G includes infants with the GG genotype. The effect of
genotype on attachment security was significant in the non-Caucasian group
(p < 0.005).
Chen et al. OXTR and attachment in humans
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August 2011 | Volume 2 | Article 200 | 4
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variants of OXTR. Closer examination of these building blocks of
social information processing may also help clarify possible associa-
tions among OXTR alleles, attachment, and autism in individuals
of different ethnicities.
One limitation of the current study is that we did not measure
either parental behavior or genotype. Nonetheless, based on other
examples in the developmental literature (Fox et al., 2005; Caspi
and Moffitt, 2006; Bakermans-Kranenburg and van IJzendoorn,
2007; Barry et al., 2008), and on work examining parenting and
gene expression in rodents (Meaney, 2001), we expect that future
studies will find that OXTR interacts with caregiving to predict
infant attachment. In addition, it is possible that the current results
are an indirect reflection of the parents’ genotype, particularly given
Bakermans-Kranenberg and van Ijzendoorn’s (2008) finding that
OXTR is related to parenting style. It should be noted however,
that whereas Bakersman-Kranenberg and van Ijzendoorn found
an association between parenting and rs53576, the association
reported here is with rs2254298. We did not find an association
between attachment status and rs53576.
The identification of different functional variants of the oxytocin
receptor gene sets the stage for beginning to examine causal dif-
ferences among alleles. These differences may lie in the functional
activity of the gene product itself, in the levels of its expression in
different brain areas or at different times, or in the sensitivity of its
expression to environmental influences. A clearer understanding
of this biology promises to help us elucidate mechanisms of social
stress-regulation that lead to individual differences in both adaptive
and maladaptive psychological functioning.
The authors thank Karen Parker and Anna Penn for their discus-
sions on the role of oxytocin in infancy and Joachim Hallmayer for
help with an earlier version of this work. Funding: This research was
supported by a Hass Foundation seed grant to Susan C. Johnson
and by Grant MH074849 from the National Institute of Mental
Health to Ian H. Gotlib.
other genetic polymorphisms that themselves vary across ethnic
populations (e.g., Chang et al., 1996; Kunugi et al., 1997). These
unmeasured differences may mask oxytocin function and inhibit
our ability to observe variations in OXTR function to a greater
extent in some populations than in others.
We may not be able to resolve these issues until we gain a more
complete understanding of the structure of the oxytocin receptor
gene. In the meantime, obtaining information about additional
OXTR SNPs in association with behavioral data should allow us
to identify haplotypes (chromosomes characterized by specific
permutations of multiple SNPs) within these initial groupings
that may have even stronger associations with particular attach-
ment phenotypes. In any case, the differences between Caucasian
and non-Caucasian infants documented in this study serve as a
reminder of the difficulties involved in generalizing genetic con-
tributions across populations.
As with all genetic association studies, our finding should be rep-
licated in an independent sample in order to establish the robust-
ness of the effect observed in our sample as well as to clarify its
effect size. Further studies of the role of OXTR in infant behavior
would be of particular relevance, as all previous studies have tested
adult samples. Given the broad confidence interval of our reported
effect in non-Caucasians, the inclusion of larger, more homogene-
ous samples in future research would be advisable. In Caucasians,
it remains to be seen whether future studies using a much larger
sample will establish a significant, reversed pattern of association
between the alleles studied and attachment status (comparable
to the opposite patterns of association in different ethnic groups
between specific alleles at rs2254298 and autism risk observed in
Attachment behaviors in infants represent a relatively gross
behavioral manifestation of infants’ underlying cognitive and emo-
tional processes. Further examination of finer-grained aspects of
social information processing and behavior is needed. Not only
will this advance our understanding of attachment processes, but
it may also facilitate the identification of additional possible allelic
Chen et al. OXTR and attachment in humans
www.frontiersin.org August 2011 | Volume 2 | Article 200 | 5
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Received: 07 July 2010; accepted: 08
August 2011; published online: 25 August
Citation: Chen FS, Barth ME, Johnson
SL, Gotlib IH and Johnson SC (2011)
Oxytocin receptor (OXTR) polymor-
phisms and attachment in human infants.
Front. Psychology 2:200. doi: 10.3389/
This article was submitted to Frontiers in
Developmental Psychology, a specialty of
Frontiers in Psychology.
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Frontiers in Psychology | Developmental Psychology
August 2011 | Volume 2 | Article 200 | 6