University of Pennsylvania
Neuroethics PublicationsCenter for Neuroscience & Society
Socioeconomic status and the brain: mechanistic
insights from human and animal research
Daniel A. Hackman
University of Pennsylvania
Martha J. Farah
University of Pennsylvania, email@example.com
Michael J. Meaney
Suggested Citation: Hackman, D.A, Farah, M.J. and Meaney, M.J. (2010). Socioeconomic status and the brain: mechanistic insights from human and
animal research.Nature Reviews.Vol. 11., 651-659.
© Nature Publishing Group: doi:10.1038/nrn2897
This paper is posted at ScholarlyCommons.http://repository.upenn.edu/neuroethics_pubs/67
For more information, please firstname.lastname@example.org.
As the field of human neuroscience has
matured, it has progressed from describ-
ing the ‘typical’ or ‘average’ human brain
to characterizing individual differences in
brain structure and function, and identify-
ing their determinants. Socioeconomic sta-
tus (SES), a measure of one’s overall status
and position in society, strongly influences
an individual’s experiences from child-
hood and through adult life. Research is
beginning to shed light on the mechanisms
through which experiences in the social
world during early childhood affect the
structure and function of the brain.
Growing up in a family with low SES is
associated with substantially worse health
and impaired psychological well-being,
and impaired cognitive and emotional
development throughout the lifespan1–6. In
contrast to sociological and epidemiological
approaches, neuroscience can identify the
underlying cognitive and affective systems
that are influenced by SES (BOX 1). In addi-
tion, neuroscience research — in animals
and in humans — has provided candidate
mechanisms for the cause–effect relation-
ships between SES and neural development.
This research has also demonstrated that
at least some of these effects are reversible.
Such a mechanistic understanding will ena-
ble the design of more specific and powerful
interventions to prevent and remediate the
effects of low childhood SES7–9.
Other recent reviews have discussed
research on SES-related differences in neuro-
cognitive development7–9. In this Perspective,
we focus on the candidate mechanisms by
which SES influences brain development,
drawing from research in humans and in
animal models. We first describe studies
in humans that show that SES influences
cognitive and affective function in children,
adolescents and young adults. We then dis-
cuss studies in human populations that have
identified possible mediators of the effects of
SES, and review research in animals in which
these factors were directly manipulated to
assess their effect on offspring outcomes.
SES effects on emotional and cognitive
development [Au: please reduce to 1 line]
SES is a complex construct that is based
on household income, material resources,
education and occupation, as well as related
neighbourhood and family characteristics,
such as exposure to violence and toxins,
parental care and provision of a cognitively
stimulating environment2,5,10,11 (for contro-
versies regarding the measurement and the
defining levels of SES see Refs 1,10,11). Not
only the lowest stratum but all levels of SES
affect emotional and cognitive development
to varying degrees1,12–14. This implies that
the effects of SES that are reviewed here are
relevant to the entire population, although it
should be noted that the strongest effects are
often seen in people with the lowest levels
Compared with children and adolescents
from higher-SES backgrounds, children
and adolescents from low-SES back-
grounds show higher rates of depression,
anxiety, attention problems and conduct
disorders12,15–18, and a higher prevalence
of internalizing (that is, depression- or
anxiety-like) and externalizing (that is,
aggressive and impulsive) behaviours
[Au:OK?] 6,19–21, all of which increase with
the duration of impoverishment12,21. In addi-
tion, childhood SES influences cognitive
development; it is positively correlated with
intelligence and academic achievement from
early childhood and through adolescence
These effects are likely to account, at least
in part, for the persistence of poverty across
generations24: individuals of low childhood
SES face various social and economic bar-
riers to success and well-being, and do so
with the added disadvantage of worse health,
reduced emotional resilience and impaired
SES and neurocognitive systems
It is difficult to discern the mechanisms that
underlie the link between SES and intel-
ligence, academic performance and mental
health because each of the outcome variables
— IQ, school achievement and diagnostic
classifications — reflect the functioning of
multiple underlying cognitive and socioe-
motional systems. Therefore, a promising
approach for understanding how SES affects
these outcome variables is to identify SES-
related differences in the underlying cogni-
tive and affective neural systems (BOX 1).
Childhood SES affects some neurocogni-
tive systems more than others. Studies that
assessed multiple neurocognitive systems
SciEncE & SociEty
Socioeconomic status and the brain:
mechanistic insights from human
and animal research
Daniel A. Hackman, Martha J. Farah and Michael J. Meaney
Abstract | Human brain development occurs within a socioeconomic context and
childhood socioeconomic status (SES) influences neural development —
particularly of the systems that subserve language and executive function.
Research in humans and in animal models has implicated prenatal factors,
parent–child interactions and cognitive stimulation in the home environment in
the effects of SES on neural development. These findings provide a unique
opportunity for understanding how environmental factors can lead to individual
differences in brain development, and for improving the programmes and policies
that are designed to alleviate SES-related disparities in mental health and
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Nature Reviews | Neuroscience
found that the largest effects of SES are on
language processing, with more moderate
effects on executive function — particu-
larly on working memory and cognitive
control13,25–27. Additionally, some studies
found moderate effects of SES on declarative
memory and spatial cognition13,25,28,29.
Studies that focus on language devel-
opment have shown an effect of SES on
vocabulary, phonological awareness (the
ability to reflect on the sound and structure
of language; an important ability for learn-
ing to read) and syntax30. For example, an
early, influential study estimated that the
vocabulary of American 3-year-olds from
professional families is twice as large as
that of children in families on welfare31.
Structural differences in temporal and pari-
etal brain areas that are involved in language
have not been found across SES levels in
children32. However, SES was positively
correlated with the degree to which the left
(relative to the right) inferior frontal gyrus
is activated during a language task in young
children33, indicative of decreased specializa-
tion of language function in the left hemi-
sphere in children with low SES. moreover,
left fusiform activity during reading was
positively correlated with phonological
awareness in lower-SES children, but not in
SES-related differences in the executive
functions of working memory and inhibi-
tory control have been noted in children
as young as 6–14 months of age35. SES-
related differences in executive attentional
systems have been reported in 6-year-old
children36, and SES-related disparities in
various tasks of executive function have
been described at multiple developmental
stages through early adolescence13,25,26,37–39.
likewise, SES influences verbal and spatial
working memory in children and adoles-
cents13,25–26,40, and spatial working memory
in late adolescence41. Some studies do not
find SES differences in all tasks of executive
function40,42–44, although this lack of effect
may be explained in part by rigorous exclu-
sion criteria, resulting in samples with par-
ticularly healthy and able low-SES children.
Studies in adults show similar SES-related
disparities in tasks measuring cognitive
flexibility, immediate verbal learning and
memory, and verbal fluency45.
There are also SES-related differences
in the degree to which specific neural sys-
tems are recruited during executive func-
tion tasks, even when task performance
does not differ between SES groups. For
example, event-related potentials (ERPs)
reveal that low-SES children exhibit larger
responses to unattended stimuli, which is
indicative of difficulty in suppressing dis-
traction early in the processing stream and
thus, of reduced selective attention46–47. In
addition, as measured with ERPs, low-SES
children do not recruit prefrontal atten-
tion circuits in response to novel distracter
stimuli to the same degree as higher-SES
children27. moreover, in a functional mRI-
based task that requires the subject to
shift between applying familiar stimulus–
response rules and learning new rules, low-
SES children preferentially recruit the right
dorsolateral prefrontal cortex (DlPFC)
when shifting to novel rules48. (The DlPFC
is a region in which activation is inversely
related to accuracy in applying the new
There is also evidence of SES-related
differences in the neural processing of
emotion. lower-SES adolescents exhibit
lower left-sided brain activity at rest, as
measured by resting alpha-asymmetry
at frontal sites, a pattern that is typically
seen in patients with depression49. Among
college students, lower subjective social
status is associated with an increased amy-
gdala response to angry faces50. In adults,
lower subjective social status is related to
a smaller volume of the perigenual ante-
rior cingulate cortex51, a region that is
functionally connected with the amygdala
and that is implicated in the regulation of
emotional states and the risk of affective
In summary, there is evidence of robust
SES differences in language and executive
function, as well as emerging evidence for
differences in other cognitive and affec-
tive processes. Executive function seems
to be particularly important in achieving
positive life outcomes despite adversity
in low-SES children and adolescents54,55.
Impairments in executive function are
also implicated in various affective and
behavioural disorders, and language devel-
opment in childhood is important for suc-
cessful school performance56–60. Individual
differences in these neurocognitive systems
are determined in part by SES and these
systems therefore emerge as candidate
pathways by which SES might compromise
academic achievement and increase the
risk of mental illness.
Box 1 | the role of neuroscience in addressing socioeconomic status-related disparities
Socioeconomic status (SES) has effects on cognition, academic achievement and mental health.
These effects reflect the combined functioning of multiple underlying brain systems and are mediated
by factors that influence the development of these systems (see the figure). [Au:oK?] Research on
brain development enables us to identify the differences in the cognitive and affective neural systems
that underlie the effects of SES on cognition, academic achievement and mental health. In addition,
neuroscience research in animals and humans can provide biologically plausible candidate mediators
for explaining the cause–effect relationships between SES and neural development. These mediators
include prenatal factors, parental care and cognitive stimulation, as well as other possible
mechanisms (BOX 2). It is also likely that the effects of SES during early childhood on cognition,
academic achievement and mental health will influence adult socioeconomic advancement. Each
aspect of this schematic (see the figure) is also a potential target for intervention and prevention
programmes. These programmes could seek to influence, firstly, SES directly; secondly, the candidate
mediators of SES effects; thirdly, aspects of brain development through strategies that include the
training of specific neurocognitive functions; and finally, school achievement or psychopathology
through changes in curricula or therapeutic treatment. By identifying novel targets for intervention
and by providing a more complete explanation of the mechanisms that cause SES-related disparities,
neuroscience research will enable the design of specific and theory-driven interventions to prevent
and remediate the effects of low childhood SES.
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Disentangling cause and effect
The association between SES and human
brain functioning could indicate that the
experiences that are typical of different
levels of SES affect brain development
(‘social causation’). Alternatively, it could
indicate that differences in brain function-
ing predispose people to a particular level
of socioeconomic success and, therefore,
to a particular SES (‘social selection’). The
two possibilities are not mutually exclusive
and may operate at different times across
development such that, for example, social
causation may explain SES-related effects
on neurocognitive development in child-
hood and adolescence, which over time may
inhibit socioeconomic achievement and
thus, SES in adulthood. In addition, it is pos-
sible that genomic variation in concert with
environmental context may influence both
family SES and child development, and that
genetic variation may interact with SES to
influence neurodevelopmental outcomes.
Nevertheless, the current evidence indicates
that SES-related differences in neural devel-
opment, at least in part, reflect social causes.
In the realm of mental health, evidence
for the social causation hypothesis of SES-
related differences in the prevalence of
depression and anxiety is strong (although
social selection may also [Au:OK?] oper-
ate in schizophrenia, as the SES of people
with schizophrenia is likely to decline as
a consequence of their illness and illness-
related impairments)18,20,61,62. moreover, a
natural ‘experiment’ in which one subset of
a population received a sudden income sup-
plement revealed that even small changes in
income for impoverished families leads to
decreased rates of childhood mental health
problems, particularly for clinically signifi-
cant externalizing behaviours63. This not
only supports the ‘social causation’ hypoth-
esis but also indicates that the excess mental
health burden of low-SES families may be at
least partly reversible by changes in income.
In addition, findings from a study of twins
indicate that the heritability of internalizing
problems can be modified by SES. Here,
the environment accounted for a greater
percentage of the variation in internalization
between twins at low-SES levels64.
In the realm of cognitive functioning
there is considerable evidence that environ-
mental contexts exert causal influence65.
Cross-fostering studies that compared chil-
dren who were adopted within or between
SES levels also found a strong environmental
component to SES-related differences in
IQ, again supporting the social causation
hypothesis66. This approach may in fact have
underestimated environmental effects, as
the implicit assumption is that prenatal envi-
ronmental factors are genetic rather than
environmental. In addition, the impact of
poverty is greater if poverty is experienced
in early rather than late childhood3,12 and
this is difficult to explain in terms of herit-
ability alone. Studies comparing mono- and
di-zygotic twins also indicate that the mag-
nitude of genetic effects on IQ depends on
SES, such that cognitive ability is almost
entirely predicted by environmental factors
at lower-SES levels67. Thus, in addition to the
known effects of genomic variation on exec-
utive function68, it is likely that the develop-
ment of executive function is influenced by
the environment, especially at lower-SES
levels. It is also worth noting that estimates
of environmental effects in studies of twins
depend on the variance in environment
across the sample, so if there is insufficient
variation in SES then overall environmen-
tal effects are likely to be underestimated.
moreover, the effects of SES and of genotype
interact to produce phenotypes such as sero-
tonin responsivity to fenfluramine [Au:OK?]
and attention ability69,70. lastly, some aspects
of neural development that are influenced
by SES, such as executive function, are also
responsive to intervention. This is consistent
with the ‘social causation’ hypothesis and
demonstrates that differences may be at least
No single environmental factor is likely
to explain all SES effects, and it is probable
that specific factors mediate specific aspects
of neurodevelopment. Two environmental
factors that could mediate SES-related dif-
ferences in neurocognitive development are
healthcare access and education, both of
which are better for children in higher levels
of SES. Yet, they cannot entirely explain SES
effects. For example, gradients of SES effects
on health persist in countries with universal
health care1, and SES effects on cognition
and neurodevelopment emerge early in
childhood, before children have extensive,
candidate mechanisms of SES effects
SES influences the quality of the physical
and psychosocial environment throughout
development5. Factors in the environment,
such as exposure to cognitive stimulation in
the home, toxins, nutrition, prenatal drug
exposure and stress — including parental
stress and its associated effects on parent-
ing practices and parent-child interactions
— might mediate the effects of SES on the
brain (BOX 2). Consequently, the challenge is
to identify the underlying mechanisms by
which SES influences brain development.
Hypotheses concerning these mechanisms
can be formed and tested by integrating data
from studies in humans and from animal
models, each of which have different and
complementary strengths and weaknesses
(BOX 3). We focus on the three potential
mechanisms underlying the effects of SES on
neurocognitive development that have the
broadest empirical support: prenatal factors,
parental care and cognitive stimulation (see
Prenatal influences. low SES in pregnant
women increases the likelihood of prema-
ture birth and impaired fetal growth73, both
of which are predictive of increased rates of
Box 2 | the ecology of socioeconomic status
In addition to parenting quality and the in utero and home environments, there are other factors that
may mediate the effects of socioeconomic status (SES) on neural development. These factors include:
•?Toxin exposure: low-SES children show increased levels of lead in the blood5. Lead is a neurotoxin
that affects IQ144 and school achievement, particularly affecting reading ability145.
•?Nutrition: nutrients and caloric intake influence the neural mechanisms that subserve cognition
and emotion146. Lower-SES families have less access to healthy foods and are more likely to
experience food insufficiency and nutritional deficiency5.
•?Prenatal drug exposure: there is little evidence that prenatal drug exposure is a major contributor
to the SES disparities noted in this article. Although alcohol and drug use during pregnancy is
related to SES, the direction of the relationship varies by substance, and alcohol use in particular
is less common in pregnant women of low SES147–148. Furthermore, the effects of prenatal cocaine
exposure seem to be relatively small when the effects of other factors, such as the home
environment, are controlled for149.
•?Stress: stress affects family relationships, including relationships with children. Low-SES families
experience increased stress related to social rank, difficulties in providing for the family’s needs,
living in dangerous neighbourhoods and other factors. This can lead to chronic stress and thereby
affect child development5,96,150,151. There is some evidence from research in animals and humans
that stress specifically impairs attentional control152,153, and that indicators of chronic stress
exposure mediate the relationship between childhood SES and working memory41.
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vOlumE 11 | SEPTEmbER 2010 | 3
childhood mental illness and poor school
performance74–78. low SES is also associated
with higher levels of stress, higher infection
rates and poor nutrition during pregnancy.
All of these increase plasma levels of cortico-
tropin-releasing factor (CRF) and glucocor-
ticoids in both the mother and the fetus76,79–81
and can thereby restrain fetal growth76,79
and trigger prematurity80. Glucocorticoid
administration during pregnancy is associ-
ated with increased externalizing behaviour,
shyness, distractibility and inattention, as
well as lower IQ in children82. moreover,
even modestly low birthweight is linked to
smaller hippocampal volume in adults83.
These findings suggest that conditions that
are associated with low SES compromise
fetal growth and neurodevelopment, with
subsequent effects on neural function that
persist into adulthood.
In rodents, pre- or peri-natal glucocor-
ticoid administration to pregnant females
reduces brain weight at birth, inhibits
neurogenesis and delays neuronal matura-
tion, myelination, gliogenesis and synapse
formation79. moreover, maternal stress
during pregnancy decreases spine density
in multiple brain areas that are related to
emotion regulation, including the hippoc-
ampus, anterior cingulate and orbitofrontal
cortex84, and increases behavioural and
hormonal responses to stress in the offspring
in adulthood76,79,85–87. The effects on stress
responsiveness in adulthood are abolished
by normalization of glucocorticoid levels
during pregnancy88. In Rhesus monkeys,
fetal exposure to elevated glucocorti-
coid levels reduces hippocampal volume
in adulthood89. The offspring of female
Rhesus monkeys that were stressed during
pregnancy exhibit decreased birthweight,
impaired neuromotor development, atten-
tion deficits and emotional dysregulation
across the lifespan90. moreover, there is evi-
dence in rodents that prenatal influences on
hypothalamus–pituitary–adrenal (HPA) axis
activity can be transmitted across genera-
tions in an epigenetic manner91 (see below).
Together, these findings suggest that in
pregnant women, stressors that are associ-
ated with low SES predict birth outcomes
that mimic the effects of increased fetal glu-
cocorticoid exposure on neurodevelopment
and that may persist across generations.
Consequently, it is likely that SES effects
might emerge during fetal development.
Parental care. Prenatal factors are unlikely
to explain all of the effects of SES on neu-
rodevelopment, particularly as SES effects
are often still apparent even after controlling
for birthweight92. Postnatal parental stress
influences child development by decreasing
parental involvement and care, as described
by the family stress model4. In humans,
low SES is associated with greater irritabil-
ity and depressed and anxious moods in
parents, which compromise parent–child
interactions93,94. Parental stress leads to harsh
and inconsistent discipline, less sensitivity to
the needs of the child, reduced verbal com-
munication and, in the children, insecure
attachment to the primary care-giver6,31,93–96.
Familial conflict and problematic parental
behaviour — including (but not limited to)
harsh and inconsistent discipline, neglect
and abuse — are associated across all levels
of SES with emotional and behavioural
problems in children. These problems
are not only observed when measured
concurrently, such that parenting quality
[Au:OK?] correlates with emotional and
behavioural patterns in the child, but also
when measured prospectively, as the quality
of [Au:OK?] earlier parenting predicts chil-
dren’s emotional and behavioural patterns
Parental care, and in particular parental
discipline, parent–child verbal communica-
tion and sensitivity to the emotional needs
of the child, at least partially mediates the
effects of SES on emotional and cognitive
function in children6,19,92,100. High-quality
parent–child interactions are associated
with resilience among children who live in
stressful, impoverished environments101.
moreover, clinical programmes that aim to
improve parenting practices in poor, high-
risk families improve behavioural and cogni-
tive outcomes in children102–104, providing
experimental evidence that is consistent with
the role of parenting as a mediator for the
effects of SES. The quality of parental care in
early childhood predicts, in a longitudinal
study of a low-SES sample, better declara-
tive memory and smaller hippocampal
volume in low-SES adolescents, and these
associations are independent of cogni-
tive stimulation (see below) and maternal
Studies in rodents and non-human
primates have revealed evidence for direct
effects of stress on the quality of mother–
infant interactions and on gene expres-
sion and neurodevelopment. In bonnet
macaques, restricted access to food is a
stressor that greatly impairs mother–infant
interactions, which in turn increases stress
reactivity in the adolescent offspring,
reflecting an enduring effect of parental
care107. likewise, in rodents, the frequency
of licking and grooming of pups by the
mother is diminished by chronic stress
imposed during pregnancy108,109. variations
in the frequency of licking and grooming
of rat pups are associated with changes in
the neural systems that regulate behav-
ioural and HPA responses to stress in
adulthood (fIG. 1). The HPA response to
Box 3 | Animal and human research
Animal models provide important insights into the effects of socioeconomic status (SES) on brain
development, despite the fact that animals do not have SES per se. Nevertheless, animal models
are able to capture many of the components and correlates of SES — including prenatal factors,
postnatal parental behaviour and cognitive stimulation — and allow for a level of experimental
control over these factors that is neither possible nor desirable in studies with humans. In addition,
in humans these putative environmental mediators of SES effects are correlated with one another.
Animal research enables their effects to be isolated and can reveal synergistic interactions among
them. Of course, there are limits to the adequacy of animal models for human development,
particularly when social and cultural phenomena are of interest. Stress that is induced
experimentally in a rat, such as by physical restraint, may not reflect [Au:oK?] the psychosocial
aspects of stress that are experienced by a human who is struggling economically. Furthermore,
the extent to which parental care or cognitive stimulation correspond between animals and
humans is undoubtedly low. Likewise, although efforts can be made to employ parallel outcome
measures of certain executive function tasks in human and animal research, animal models of
language performance or certain aspects of executive function, such as verbal working memory,
are lacking. In humans these factors are nested within larger contexts that may be influential for
SES [Au:oK?], for example, there are differences between rural and urban poverty5. [Au:oK?] It is
therefore crucial to test hypotheses concerning the underlying causes of SES effects directly, by
means other than experimental manipulation of the key candidate mechanisms in animal models.
This can be accomplished using statistical mediation analysis, natural experiments, intervention
studies71,142 and strategies such as repeated, time-lagged measurements, structural equation
modelling and propensity scores1 to help to strengthen causal inferences. Using neuroimaging and
molecular measures as well as the more conventional behavioural measures, this approach could
in principle investigate specific neural mechanisms that research in animals has suggested may
underlie the effects of SES on cognition and mental health. [Au:oK?]
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(maternal licking and grooming)
Low maternal licking
High licking maternal
↓ GR expression
↑ GR expression
High corticosterone levels
Low licking or grooming
Low corticosterone levels
High licking or grooming
stress in mammals is largely mediated by
the release of CRF from the hypothalamus,
which is under negative feedback control
from glucocorticoids, in part through the
activation of glucocorticoid receptors in the
hippocampus. The adult offspring of dams
that exhibit high licking and grooming of
pups show increased hippocampal gluco-
corticoid receptor expression, decreased
hypothalamic CRF levels and more modest
HPA responses to stress compared with
the offspring of dams that exhibit low lick-
ing and grooming110–114. Adult offspring
of mothers that exhibit high licking and
grooming also have enhanced expression
of genes for GAbAA (γ-aminobutyric acid
type A) receptor subunits in the amygdala
that regulate inhibitory influences over
stress responses, rendering the animals
less fearful110,111. Cross-fostering studies
in rats have revealed direct effects of post-
natal maternal care (that is, independent
of genomic influences) on hippocampal
physiology and on the response to stress in
the adult offspring111,113. Importantly, in rats,
chronic stress during pregnancy alters the
quality of mother–infant interactions107,108,
reducing the frequency of pup-licking in the
dam and increasing stress reactivity in the
offspring113, and these effects can be trans-
mitted across generations115. These find-
ings recapitulate the theme that is apparent
in studies of SES and human parenting,
namely that stressful environments alter
the quality of parenting and thus, the
Studies in rats have suggested that epi-
genetic mechanisms mediate the effect of
maternal care on hippocampal glucocorti-
coid receptor expression. This mechanism
involves DNA methylation, which affects
chromatin structure and thereby regulates
transcription factor binding and subse-
quently, gene transcription116. As adults, the
offspring of mothers that exhibit high lick-
ing and grooming show decreased cytosine
methylation of the binding site for the tran-
scription factor nerve growth factor-induci-
ble A (NGFIA, also known as EGR1) that lies
within the exon 17 promoter of N1r3c1 (the
gene that encodes the glucocorticoid receptor
in the hippocampus; this results in increased
NGFIA binding to this promoter, increased
hippocampal glucocorticoid receptor expres-
sion and more modest HPA responses to
stress114,117,118. In humans, child abuse is asso-
ciated with increased methylation of the exon
1F glucocorticoid receptor gene promoter
(the homologue of exon 17 in rats) in the
hippocampus119. These findings suggest that
the effects of parental care may be mediated
through a similar epigenetic mechanism in
humans, although it remains to be investi-
gated whether differences in childhood SES
are associated with differences in DNA meth-
ylation and gene expression.
variations in maternal care in rats also
influence synaptic development in brain
regions that regulate cognitive function.
licking and grooming of pups increases
NmDA (N-methyl-d-aspartate) receptor
Figure 1 | Parental regulation of the hypothalamic–pituitary–adrenal axis. a | The current work-
ing model for the effect of maternal care (specifically, of licking and grooming pups) on the epigenetic
regulation of the expression of Nr3c1, the gene that encodes the glucocorticoid receptor (GR). Licking
and grooming of pups activates thyroid hormone-dependent increases in hippocampal serotonin
(5-hydroxytryptamine or 5-HT) levels and 5-HT binding to the 5-HT7 receptor. Activation of the 5-HT7
receptor leads to the activation of a cyclic AMP–protein kinase A (PKA) cascade that induces the
expression of the transcription factor nerve growth factor-inducible A (NGFiA) and cyclic AMP
response element-binding (cREB) protein (cBP) expression and their association with the neuron-
specific exon 17 GR gene promoter. [Au:oK?] b | in neonates, high levels of licking increases NGFiA
and cBP association with the exon 17 promoter by triggering demethylation of a dinucleotide
sequence (cpG) that is located within the NGFiA binding region of the exon. This subsequently
increases the ability of NGFiA to activate GR gene expression. M, methylation. c | A schematic of the
hypothalamic–pituitary–adrenal axis, the pivot [Au:oK?] of which are the corticotropin-releasing fac-
tor (cRF) neurons of the paraventricular nucleus of the hypothalamus. cRF is released into the portal
system of the anterior pituitary, stimulating the synthesis and release of adrenocorticotropin (AcTH),
which then stimulates adrenal glucocorticoid release. Glucocorticoids act on GRs in multiple brain
regions, including the hippocampus, to inhibit the synthesis and release of cRF (that is, glucocorticoid
negative feedback takes place). The adult offspring of mothers that exhibit high licking and grooming,
by comparison to those of low licking and grooming dams, show increased GR expression, enhanced
negative-feedback sensitivity to glucocorticoids, reduced cRF expression in the hypothalamus and
more modest pituitary–adrenal responses to stress.
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levels in the hippocampus and hippocampal
expression of growth factors (brain-derived
neurotrophic factor and basic fibroblast
growth factor), which promote neuronal
activation and synaptogenesis, respec-
tively120,121. The adult offspring of mothers
that exhibit high licking and grooming show
increased synaptic density120,122 and a greater
capacity for synaptic plasticity in the hip-
pocampus and prefrontal cortex (in vivo123
or in vitro122), and improved performance in
hippocampal and prefrontal cortex-depend-
ent forms of learning and memory120,123. The
effects on synaptic development and cogni-
tive performance are reversed with cross-
fostering120, indicating that parental care has
direct effects on neuronal development that
are consistent with those reported in studies
of cognitive development in children.
It should be noted that although the
majority of the research described above
focuses on maternal care, particularly in ani-
mal models, it is not necessarily the case that
in humans only mother–child interactions
influence the cognitive and emotional devel-
opment of offspring. It is likely that nurtur-
ing and supportive care-giving by parents
of either gender or by other members of the
community is important for child develop-
ment124. The important point is that broader
social and economic context can influence
the quality of parental care, which then
influences the activity of the neural systems
that regulate stress reactivity and cognition
in offspring through the epigenetic regula-
tion of gene expression.
The home environment: cognitive stimulation.
SES influences the level of cognitive stimula-
tion in the home, as described by the family
investment model4,6. The quality of cognitive
stimulation in the home includes, but is not
limited to, factors such as the availability
of books (and other literacy resources),
computers, trips and parental communica-
tion. Together, these factors can explain the
effects of SES on cognitive ability in children
(for example, on reading and mathematics
skills12,19,21,23,92,125,126) even when maternal IQ
has been controlled for. The effect may be
fairly specific as, in a longitudinal study, the
level of cognitive stimulation in early child-
hood predicts language-related skills in low-
SES adolescents independently of the quality
of parental care and maternal intelligence105.
Additional evidence for these effects
emerges from studies of intervention pro-
grammes that enhance cognitive stimula-
tion. Such programmes buffer [Au:OK?]
the effects of low SES on cognitive develop-
ment6, boost school readiness127 and promote
academic achievement128, even in studies
in which baseline cognitive functioning
and maternal education have been control-
led for129. Such interventions also increase
self-esteem and social competence129, and
reduce aggression130, particularly among the
most deprived children131. The key point
is that the effects of poverty on specific
cognitive outcomes can be reversed, in
part, through enhanced cognitive stimula-
tion. long-term follow-up observations of
the effects of early intervention, including
randomized controlled trials, come from
programmes such as the Perry Preschool
Program (michigan, uSA), the Abecedarian
Project (North Carolina, uSA) and the
Chicago Child–Parent Centers, uSA. These
include increased cognitive stimulation as
part of more comprehensive intervention
programmes. Intervention programmes
caused higher scores on achievement tests,
higher levels of education and income, and
lower rates of incarceration decades after
the completion of the programmes, despite
the fact that in some studies the initial gains
in IQ disappeared132–135. Such effects suggest
that although experience at any age affects
later outcomes, early cognitive stimulation is
a particularly important determinant of later
Animal models also provide a strong
rationale for cognitive stimulation as a
mediator of SES effects on neural develop-
ment. Hebb observed that environmental
complexity during development alters a
wide range of neural functions136. Studies
of environmental enrichment in which
animals are housed under conditions that
provide increased sensory, cognitive and
motor stimulation (usually accompanied
by increased social complexity) show that
enrichment upregulates the expression of
cellular signals that are involved in activity-
dependent synapse formation. This includes
factors that are involved in glutamatergic
signalling137, neurotrophins (including
insulin-like growth factor 1, nerve growth
factor, brain-derived neurotrophic factor
and glial-derived neurotrophic factor), and
synaptic proteins that are involved in synap-
tic proliferation and function138. Enrichment
therefore increases dendritic branching,
gliogenesis and synaptic density in the hip-
pocampus and cortex, and promotes hip-
pocampal neurogenesis and the integration
of newly generated neurons into functional
circuits138–140. These enrichment effects are
associated with improved performance in
tests of spatial learning and memory138.
Rodents that were exposed to adversity in
early life are more sensitive to environmental
enrichment in adolescence120,137,140. Thus,
basic neuroscience research shows how
neurodevelopment is affected by variations
in cognitive stimulation, a characteristic that
often relates to SES.
conclusions and policy implications
SES influences cognitive and emotional
development. Nevertheless, the concept of
SES has long been ignored in neuroscience,
perhaps because of the complexity of the
construct and the difficulty of experimen-
tally controlling its many components. The
research discussed here suggests that SES
can be understood within the framework
of neuroscience research. Childhood SES
influences the development of specific
neural systems. The biological nature of
these SES-related differences may be easily
misinterpreted as more ‘essential’, innate or
immutable than SES-related differences in
behaviour. However, as reviewed here, there
is little evidence for such a claim. Instead,
studies in humans suggest that prenatal
factors, parent–offspring interactions and
cognitive stimulation at least partly underlie
the effects of SES on brain development.
These effects are somewhat specific, with the
level of cognitive stimulation in the home
environment best predicting a child’s cogni-
tive development and the quality of parental
care more closely related to its emotional
development. Studies in non-human animals
support the biological plausibility of these
explanations. However, future research is
required to confirm that these factors indeed
account for SES effects on neural develop-
ment and to apply this work to the develop-
ment of more effective interventions.
Although these are early days for the
study of SES and brain development, the
integration of social and neural approaches
to SES has a number of policy implications.
First, it highlights brain development as a
new target for intervention and prevention
programmes (BOX 1). until now, interven-
tions have been targeted at changing SES
directly by increasing family income63,141,
influencing the putative mediators of
SES effects, such as parenting style, and
influencing academic achievement and
psychopathology through direct interven-
tions, including educational or treatment
programmes targeted at low-SES communi-
ties. The targeting of brain development
has involved familiar approaches, such
as improving children’s access to medi-
cal care or nutritional supplementation.
more recently, it has included programmes
aimed at training particular neurocogni-
tive systems directly, for example by using
6 | SEPTEmbER 2010 | vOlumE 11
computerized, game-based strategies for
training executive functions or school cur-
ricula that employ specific exercises as
well as overarching strategies to promote
executive functions throughout the school
day60,71,72. Such approaches seem to be
promising from the perspective of basic
neuroscience research, but future studies
must empirically determine if such pro-
Second, our emerging understanding of
SES-related differences in neurocognitive
systems places these disparities into a broad
public health perspective. Converging evi-
dence that differences in levels of parental
care and cognitive stimulation in the home
underlie SES-related differences in brain
development highlight the importance of
policies that shape the broader environments
to which families are exposed. This evidence
extends the discussion of child development
beyond traditional policy arenas such as
education and child-care. Precedence should
be given to improving care for children and
to providing enriching environments during
pre- and post-natal development. [Au:OK?]
Therefore, policies and programmes that
reduce parental stress, enhance parental
emotional well-being and provide adequate
resources for parents and communities
should be prioritized. [Au:OK?] moreover,
as women are often a child’s primary car-
egiver, the effects reviewed here emphasize
the significance of women’s health, emo-
tional well-being, material resources and
education for child development142.
The incorporation of SES into neuro-
science research will become increasingly
important as neuroscience is brought to
bear in educational, marketing and forensic
contexts. The applications of neuroscience
in these contexts are often developed on
the basis of findings in [Au:OK?] largely
middle-SES subjects and therefore may not
be broadly applicable to the population143.
Neuroscience research has a unique role
in synthesizing approaches from multiple
disciplines that include sociology, medicine,
public health, psychology and psychiatry
to characterize SES-related differences in
neural development and to chart the mecha-
nisms through which childhood experience
affects neural function. First, a neuroscience
approach permits us to identify the neural
phenotypes related to SES that underlie
cognitive performance and mental health,
and the potential targets for intervention.
Second, an understanding of brain develop-
ment in humans and animal models can be
leveraged to define the causal relationship
between ‘SES-related exposures’ and neural
development. The investigation of SES and
neural development is a promising area of
study that, by delineating environmental
influences on individual differences in
neural development, can refine strategies to
address SES-related disparities.
Daniel A. Hackman and Martha J. Farah are at the
Center for Cognitive Neuroscience, Center for
Neuroscience and Society, Department of Psychology,
University of Pennsylvania, 3720 Walnut Street,
Room B51, Philadelphia, Pennsylvania 19104‑6241,
Michael J. Meaney is at the Douglas Mental Health
University Institute, McGill University, Montreal,
Quebec H4H 1R3, Canada; Sackler Program for
Epigenetics and Psychobiology at McGill University,
Montrea, Quebec H3A 2T5, Canada and the Singapore
Institute for Clinical Sciences, 30 Medical Drive,
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We thank our funding institutions for their support of our
research and in the preparation of this article. M.J.M. was
supported by grants from the US National Institute of Health,
Child Health and Human Development (NICHD grant XXXXX),
the Canadian Institutes for Health Research (grant XXXXXX),
the Natural Sciences and Engineering research Council of
Canada (grant XXXXXXX) and the Hope for Depression
Research Foundation (grant XXXXX). M.J.F and D.A.H were
supported by grants from the NICHD (grant R01-HD055689),
the US National Institute on Drug Abuse (NIDA grant
R01-DA14129), the US [AU:OK?] Office of Naval Research
(grant N000140710034) and the MacArthur Foundation
Law and Neuroscience Project. We also thank K. Matula for
her assistance with references. [Au: would you like to specify
the grant numbers?]
Competing interests statement
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vOlumE 11 | SEPTEmbER 2010 | 9
Daniel A. Hackman is a doctoral candidate with clinical training,
in the Department of Psychology at the university of Pennsylvania,
Philadelphia, Pennsylvania, uSA. He studies the effect of socio-
economic status on multiple indices of neurodevelopment, as well
as the mechanisms that underlie this relationship, with a particular
focus on executive function, parental nurturance and stress physi-
ology. He has worked in health policy and is interested in using
neurodevelopmental approaches to enhance intervention and pre-
vention strategies with at-risk children and adolescents.
martha J. Farah is the Walter H. Annenberg Professor of Natural
Sciences at the university of Pennsylvania, Philadelphia,
Pennsylvania, uSA, where she directs the Center for Neuroscience
and Society. Her work has addressed many aspects of cognitive neu-
roscience, including visual perception, attention, mental imagery,
semantic memory, reading and prefrontal function. In recent years
her research has focused on the effects of poverty on brain develop-
ment, and she has been active in helping to establish the new field of
michael J. meaney completed his m.A. in child clinical psychology
and his Ph.D. in neurobiology, with post-doctoral studies in molec-
ular biology at the mcEwen laboratory of Rockefeller university,
New York, New York, uSA. He has been in the Department of
Psychiatry (Douglas mental Health university Institute) at mcGill
university, montreal, Quebec, Canada, since 1984 where he is a
James mcGill Professor of medicine. His laboratory focuses on
the mechanisms underlying the enduring effects of variations in
maternal care on gene expression and neural function using rodent
and, more recently, non-human primate models. He also leads a
longitudinal study of child development (the maternal Adversity,
vulnerability and Neurodevelopment [mAvAN] project).
000 socioeconomic status and the brain:
mechanistic insights from human and
Daniel A. Hackman, Martha J. Farah and Michael J.
Socioeconomic status (SES) influences brain
development. Farah and colleagues show that
prenatal factors, parent–child interactions and
cognitive stimulation mediate this effect, and
show that intervention at these levels can alleviate
SES-related disparities in mental health and academic
achievement. [Au:ok? Word limit is 40 words.]