Two extant evolutionary models, biological sensitivity to context theory (BSCT) and differential susceptibility theory (DST), converge on the hypothesis that some individuals are more susceptible than others to both negative (risk-promoting) and positive (development-enhancing) environmental conditions. These models contrast with the currently dominant perspective on personal vulnerability and environmental risk: diathesis stress/dual risk. We review challenges to this perspective based on emerging theory and data from the evolutionary, developmental, and health sciences. These challenges signify the need for a paradigm shift in conceptualizing Person × Environment interactions in development. In this context we advance an evolutionary–neurodevelopmental theory, based on DST and BSCT, of the role of neurobiological susceptibility to the environment in regulating environmental effects on adaptation, development, and health. We then outline current thinking about neurogenomic and endophenotypic mechanisms that may underpin neurobiological susceptibility, summarize extant empirical research on differential susceptibility, and evaluate the evolutionary bases and implications of BSCT and DST. Finally, we discuss applied issues including methodological and statistical considerations in conducting differential susceptibility research; issues of ecological, cultural, and racial–ethnic variation in neurobiological susceptibility; and implications of differential susceptibility for designing social programs. We conclude that the differential susceptibility paradigm has far-reaching implications for understanding whether and how much child and adult development responds, for better and for worse, to the gamut of species-typical environmental conditions.

Evidence indicates that maternal prenatal distress predicts problematic health and behavioral outcomes in children as well as infant/child cortisol levels and negative emotionality as reviewed here. Evidence that these physiological and behavioral characteristics themselves moderate environmental effects on development in a “for better and for worse” manner consistent with Belsky's differential susceptibility hypothesis and Boyce and Ellis' notions of biological sensitivity to context raises the prospect that susceptibility to rearing is a function of nurture (i.e., fetal environment), consistent with Boyce and Ellis' proposal that plasticity can be shaped by developmental experience. This hypothesis is supported by new findings from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development showing that low birth weight, a marker for an adverse prenatal environment, predicts infant difficult temperament, which is a susceptibility factor that we previously showed as moderating, in a for better and for worse manner, the effects of parenting and child care quality on socioemotional functioning. Moreover, recent Gene × Environment interaction research raises the prospect that some fetuses may be more susceptible to such “prenatal programming of postnatal plasticity” as a result of their genetic makeup. If this proves true, it will be consistent with the conclusion that early developmental plasticity is a function of both nature and nurture and may be evolutionarily adaptive, a further possibility considered in the discussion.

In the current paper we present new empirical data and meta-analytic evidence for the role of dopamine-related genes as a susceptibility factor interacting with the rearing environment for better and for worse, that is, increasing children's susceptibility to both the adverse effects of unsupportive environments and the beneficial effects of supportive rearing. In Study 1 we examined the readiness of 91 7-year-old children to donate their money to a charity (UNICEF). We tested whether the association between attachment and donating behavior was moderated by the presence of the dopamine receptor D4 (DRD4) 7-repeat allele. The attachment story completion task was used to assess attachment as an index of the quality of the rearing environment. Children with secure attachment representations donated more but only if they had the DRD4 7-repeat allele. In Study 2 we present the results of a meta-analysis of gene–environment studies on children up to 10 years of age involving dopamine-related genes (dopamine receptor D2, DRD4, dopamine transporter). The cumulative negative effects of these “risk genes” and adverse rearing environments have been stressed, but potentially cumulative positive effects of these same genes interacting with positive rearing environments remained largely unnoticed. We examined the associations between negative and positive rearing environments and developmental outcomes as moderated by dopamine-related gene polymorphisms. Children with the less efficient dopamine-related genes did worse in negative environments than the comparisons without the “genetic risk,” but they also profited most from positive environments. Findings are discussed in light of evolutionary theory, and illustrated with some practical implications of differential susceptibility.

Theoretical considerations and new empirical evidence suggest that children's development cannot simply be explained by either genes or environment but that their interaction is important to understanding child behavior. In particular, a genetic polymorphism, the exon III repeat region of the dopamine receptor D4, has been the focus of interest regarding differential susceptibility to parental influence. To study environmental and genetic influences on children's prosocial behavior, 168 twin pairs (mean age = 44 months) participated in an experiment that assessed prosocial behavior via three measures: compliant prosocial behavior elicited in response to social requests, self-initiated prosocial behavior enacted voluntarily, and mothers' rating of children's behavior. Genetic effects accounted for 34% to 53% of the variance in prosocial behavior. The rest of the variance was accounted for by nonshared environment and error. Parenting measures of maternal positivity, negativity, and unexplained punishment did not correlate significantly with children's prosocial behavior. However, when parenting was stratified by presence or absence of the child's dopamine receptor D4 7-repeat allele in an overlapping sample of 167 children to model differential susceptibility to parental influence, a richer picture emerged. Positive parenting related meaningfully to mother-rated prosocial behavior, and unexplained punishment related positively to self-initiated prosocial behavior, but only among children carrying the 7-repeat allele. The findings demonstrate that a molecular genetic strategy, based on genotyping of common polymorphisms and combined with a classic twin approach, provides a richer description of how genes and environment interact to shape children's behavior, and allows for the identification of differential sensitivity to parental influence.

Age at menarche, a sentinel index of pubertal maturation, was examined in relation to early family relationships (conflict, cohesion) and polymorphic variation in the gene encoding estrogen receptor-α (ESR1) in a midlife sample of 455 European American women. Consistent with prior literature, women who reported being raised in families characterized by close interpersonal relationships and little conflict tended to reach menarche at a later age than participants reared in families lacking cohesion and prone to discord. Moreover, this association was moderated by ESR1 variation, such that quality of the family environment covaried positively with menarcheal age among participants homozygous for minor alleles of the two ESR1 polymorphisms studied here (rs9304799, rs2234693), but not among women of other ESR1 genotypes. In addition, (a) family relationship variables were unrelated to ESR1 variation, and (b) genotype-dependent effects of childhood environment on age at menarche could not be accounted for by personality traits elsewhere shown to explain heritable variation in reported family conflict and cohesion. These findings are consistent with theories of differential susceptibility to environmental influence, as well as the more specific hypothesis (by Belsky) that girls differ genetically in their sensitivity to rearing effects on pubertal maturation.

Guided by evolutionary–developmental theories of biological sensitivity to context and reproductive development, the current research examined the interactive effects of early family environments and psychobiologic reactivity to stress on the subsequent timing and tempo of puberty. As predicted by the theory, among children displaying heightened biological sensitivity to context (i.e., higher stress reactivity), higher quality parent–child relationships forecast slower initial pubertal tempo and later pubertal timing, whereas lower quality parent–child relationships forecast the opposite pattern. No such effects emerged among less context-sensitive children. Whereas sympathetic nervous system reactivity moderated the effects of parent–child relationships on both breast/genital and pubic hair development, adrenocortical activation only moderated the effect on pubic hair development. The current results build on previous research documenting what family contexts predict variation in pubertal timing by demonstrating for whom those contexts matter. In addition, the authors advance a new methodological approach for assessing pubertal tempo using piecewise growth curve analysis.

Growing evidence supports the biological sensitivity to context theory, which posits that physiologically reactive children, as indexed by autonomic nervous system (ANS) reactivity to laboratory stressors, are more susceptible to both negative and positive environmental influences than their low reactive peers. High biological sensitivity is a risk factor for behavioral and health problems in the context of high adversity, whereas in contexts of low adversity it has been found to promote positive adaptation. However, several studies have shown the opposite effect, finding that children who exhibited high ANS reactivity in response to interpersonal stressors were buffered from the deleterious effects of marital conflict, whereas children who showed low ANS reactivity were more vulnerable to high levels of marital conflict. Using an ethnically diverse sample of 260 kindergartners (130 girls, 130 boys), the current study investigated whether the interaction effect of marital conflict and the two branches of ANS reactivity on children's externalizing and internalizing symptoms differs with the nature of the laboratory challenge task used to measure children's stress response. As hypothesized, results indicate that the interaction between ANS reactivity and marital conflict significantly predicted children's behavior problems, but the direction of the effect varied with the nature of the challenge task (i.e., interpersonal or cognitive). This study illustrates the importance of considering the effect of laboratory stimuli when assessing whether children's ANS reactivity moderates the effects of adversity exposure on adaptation.

It has been suggested that biological factors confer increased sensitivity to environmental influences on depressive symptoms during adolescence, a crucial time for the onset of depressive disorders. Given the critical role of the hippocampus in sensitivity to stress and processing of contextual aspects of the environment, investigation of its role in determining sensitivity to environmental context seems warranted. This study prospectively examined hippocampal volume as a measure of sensitivity to the influence of aggressive maternal behavior on change in depressive symptoms from early to midadolescence. The interaction between aggressive maternal behavior and hippocampal volume was found to predict change in depressive symptoms. Significant sex differences also emerged, whereby only for girls were larger bilateral hippocampal volumes more sensitive to the effects of maternal aggressive behavior, particularly with respect to experiencing the protective effects of low levels of maternal aggressiveness. These findings help elucidate the complex relationships between brain structure, environmental factors such as maternal parenting style, and sensitivity to (i.e., risk for, and protection from) the emergence of depression during this life stage. Given that family context risk factors are modifiable, our findings suggest the potential utility of targeted parenting interventions for the prevention and treatment of adolescent depressive disorder.

This randomized controlled trial examined (a) the efficacy of a brief intervention designed to increase the rate of secure infant attachment, (b) the differential susceptibility hypothesis, and (c) whether maternal attachment styles moderated the expected Treatment × Irritability interaction in predicting infant attachment outcomes. Although there was no main effect of treatment, a significant Treatment × Irritability interaction revealed intervention effects for the highly irritable infants only, thus supporting one of two predictions of the differential susceptibility hypothesis: highly irritable infants would have disproportionately better outcomes than moderately irritable infants in better conditions (i.e., with intervention). When separate analyses were conducted with maternal attachment styles, we found significant three-way interactions among treatment, irritability, and each of the examined maternal attachment style dimensions (i.e., secure–fearful and dismissing–preoccupied). Specifically, with more secure mothers, beneficial effects of intervention emerged for highly irritable infants. For more dismissing mothers, the results revealed support for both predictions of the differential susceptibility hypothesis: highly irritable infants, compared to moderately irritable infants, were both more likely to be secure with intervention and less likely to be secure when in the control group. It is interesting that, for more preoccupied mothers, a treatment effect emerged only for moderately irritable infants. We discuss the implications of these findings for the differential susceptibility hypothesis as well as for early intervention.

The moderating effects of biological sensitivity to context (physiological and behavioral stress reactivity) on the association between the early teacher–child relationship and the development of adolescent mental health problems were examined in a community sample of 96 children. Grade 1 measures of biological sensitivity to context included physiological (i.e., slope of mean arterial pressure across a 20- to 30-min stress protocol) and behavioral (i.e., temperamental inhibition/disinhibition) markers. Grade 1 measures of the teacher–child relationship included positive (i.e., closeness) and negative (i.e., conflict) qualities. Mental health symptoms were assessed at Grades 1 and 7. Results of a multiple regression analysis indicated substantial association of the teacher–child relationship with the development of adolescent mental health symptoms, especially for more reactive children. In addition to teacher–child relationship main effects, all four Reactivity × Teacher–Child Relationship interaction terms were statistically significant when controlling for Grade 1 symptom severity, suggesting that both physiological and behavioral reactivity moderate the association of both adverse and supportive aspects of the teacher–child relationship with Grade 7 symptom severity over and above Grade 1 severity. There were important differences, depending on which stress reactivity measure was considered. The importance of these findings for recent theoretical arguments regarding biological sensitivity to context and differential susceptibility is discussed.

This investigation examined the neural and personality correlates of processing infant facial expressions in mothers with substantiated neglect of a child under 5 years old. Event-related potentials (ERPs) were recorded from 14 neglectful and 14 control mothers as they viewed and categorized pictures of infant cries, laughs, and neutral faces. Maternal self-reports of anhedonia and empathy were also completed. Early (negative occipitotemporal component peaking at around 170 ms on the scalp [N170] and positive electrical potential peaking at about 200 ms [P200]) and late positive potential (LPP) components were selected. Both groups of mothers showed behavioral discrimination between the different facial expressions via reaction time and accuracy measures. Neglectful mothers did not exhibit increased N170 amplitude at temporal leads in response to viewing crying versus laughing and neutral expressions compared to control mothers. Both groups had greater P200 and LPP amplitudes at centroparietal leads in response to viewing crying versus neutral facial expressions. However, neglectful mothers displayed an overall attenuated brain response in LPP that was related to their higher scores in social anhedonia but not to their empathy scores. The ERP data suggest that the brain's failures in the early differentiation of cry stimuli and in the sustained processing of infant expressions related to social anhedonia may underlie the insensitive responding in neglectful mothers. The implications of these results for the design and evaluation of preventive interventions are discussed.

The differential susceptibility to parenting model was examined in relation to toddler self-regulation in a prospective longitudinal study of infants born preterm or low birth weight. We followed 153 mother–infant dyads across five time points between the infant's Neonatal Intensive Care Unit stay and 24 months postterm. Assessments of infant temperament, quality of early parenting interactions, contextual variables, and toddler effortful control and behavior problems were conducted. Results supported differential susceptibility and dual risk models in addition to documenting main effects of early parenting on children's emerging self-regulation. Our data suggested that preterm or low birth weight infants who were prone to distress or rated by mothers as more difficult were particularly susceptible to the effects of early negative parenting.

The efficacy of a short-term attachment-based intervention for changing risk outcomes for children of maltreating families was examined using a randomized control trial. Sixty-seven primary caregivers reported for maltreatment and their children (1–5 years) were randomly assigned to an intervention or control group. The intervention group received 8 weekly home visits directed at the caregiver–child dyad and focused on improving caregiver sensitivity. Intervention sessions included brief discussions of attachment–emotion regulation-related themes and video feedback of parent–child interaction. Comparison of pre- and posttest scores revealed significant improvements for the intervention group in parental sensitivity and child attachment security, and a reduction in child disorganization. Older children in the intervention group also showed lower levels of internalizing and externalizing problems following intervention. This is the first study to demonstrate the efficacy of short-term attachment-based intervention in enhancing parental sensitivity, improving child security, and reducing disorganization for children in the early childhood period.

The relationship of maternal hostile and depressive moods to children's downregulation of unprovoked anger and sadness/fear was assessed in a community sample of 267 5-year-old boys and girls. The speed of children's downregulation of unprovoked anger and sadness/fear was based on real-time observations during mother–child interaction. The association of downregulation with maternal mood was estimated using Bayesian event history analysis. As mothers reported higher depressive mood, both boys and girls were faster to downregulate anger displays as those displays accumulated during mother child interaction. The speed of boys' downregulation of anger and of sadness/fear was not associated with maternal hostile mood. As mothers reported more hostile mood, girls were faster to downregulate displays of sadness/fear, but the speed of this downregulation slowed as those displays accumulated during ongoing mother–child interaction. These associations of child downregulation and maternal mood were observed after controlling for child adjustment. The data suggest frequent exposure to different negative maternal moods affect children's expression and regulation of emotions in relatively specific ways, conditional on the type of maternal mood, the type of child emotion, and child gender.

Using data from two long-term longitudinal projects, we investigated reciprocal relations between maternal reports of physical discipline and teacher and self-ratings of child externalizing behavior, accounting for continuity in both discipline and externalizing over time. In Study 1, which followed a community sample of 562 boys and girls from age 6 to 9, high levels of physical discipline in a given year predicted high levels of externalizing behavior in the next year, and externalizing behavior in a given year predicted high levels of physical discipline in the next year. In Study 2, which followed an independent sample of 290 lower income, higher risk boys from age 10 to 15, mother-reported physical discipline in a given year predicted child ratings of antisocial behavior in the next year, but child antisocial behavior in a given year did not predict parents' use of physical discipline in the next year. In neither sample was there evidence that associations between physical discipline and child externalizing changed as the child aged, and findings were not moderated by gender, race, socioeconomic status, or the severity of the physical discipline. Implications for the reciprocal nature of the socialization process and the risks associated with physical discipline are discussed.

Transactional models suggest that peer victimization results from both individual and context differences, and understanding these differences may point to important targets for prevention and interventions that reduce victimization. Multilevel modeling was used to examine within-person (aggression and emotional dysregulation), between-person (sex and age), and between-school (participation in a victimization prevention program) factors that influence changes in physical and relational victimization over the first three years of elementary school. Children (n = 423) reported their experiences of peer victimization at entry into Grade 1 and at the end of Grade 1, Grade 2, and Grade 3. On average, trajectories of both physical and relational victimization declined. However, for individual children, teacher-rated aggression was associated with increases in physical and relational victimization, while emotional dysregulation was associated with attenuation of longitudinal declines in physical victimization and increases in relational victimization. Individual differences in sex and age at entry into Grade 1 did not significantly influence victimization trajectories over Grades 1 to 3. Children who participated in the WITS® victimization prevention program showed significant declines in physical and relational victimization. Levels of victimization among nonparticipants remained stable. Implications of child and context characteristics for preventing peer victimization in elementary school are discussed.

This prospective longitudinal study focused on self-regulatory, social–cognitive, and parenting precursors of individual differences in children's peer-directed aggression at early school age. Participants were 199 3-year-old boys and girls who were reassessed following the transition to kindergarten (5.5–6 years). Peer aggression was assessed in preschool and school settings using naturalistic observations and teacher reports. Children's self-regulation abilities and theory of mind understanding were assessed during a laboratory visit, and parenting risk (corporal punishment and low warmth/responsiveness) was assessed using interview-based and questionnaire measures. Individual differences in children's peer aggression were moderately stable across the preschool to school transition. Preschool-age children who manifested high levels of aggressive peer interactions also showed lower levels of self-regulation and theory of mind understanding, and experienced higher levels of adverse parenting than others. Our main finding was that early corporal punishment was associated with increased levels of peer aggression across the transition from preschool to school, as was the interaction between low maternal emotional support and children's early delays in theory of mind understanding. These data highlight the need for family-directed preventive efforts during the early preschool years.

This study examined the relations among temperament, emotion regulation, and depressive symptoms in early adolescents. Early adolescents provided self-reports of temperament on two occasions, as well as reports on emotion regulation and depressive symptomatology. Furthermore, 163 of these adolescents participated in event-planning and problem-solving interactions with their mothers. Adolescents with temperaments that were high in negative emotionality or low in effortful control displayed more emotionally dysregulated behaviors during the interaction tasks, reported having maladaptive responses to negative affect more often and adaptive responses less often, and had more depressive symptoms. In particular, adolescents with the high negative emotionality and low effortful control temperament combination reported the highest levels of depressive symptomatology. Sequential analyses of family interactions indicated that adolescents with more depressive symptoms were more likely to reciprocate their mothers' negative affective behaviors. Adolescents' adaptive and maladaptive responses to negative affect mediated the associations between their temperament and concurrent depressive symptoms.

Extensive developmental research has linked peer rejection during adolescence with a host of psychopathological outcomes, including depression. Moreover, recent neuroimaging research has suggested that increased activity in the subgenual region of the anterior cingulate cortex (subACC), which has been consistently linked with depression, is related to heightened sensitivity to peer rejection among adolescents. The goal of the current study was to directly test the hypothesis that adolescents' subACC responses are predictive of their risk for future depression, by examining the relationship between subACC activity during peer rejection and increases in depressive symptoms during the following year. During a functional magnetic resonance imaging scan, 20 13-year-olds were ostensibly excluded by peers during an online social interaction. Participants' depressive symptoms were assessed via parental reports at the time of the scan and 1 year later. Region of interest and whole-brain analyses indicated that greater subACC activity during exclusion was associated with increases in parent-reported depressive symptoms during the following year. These findings suggest that subACC responsivity to social exclusion may serve as a neural marker of adolescents' risk for future depression and have implications for understanding the relationship between sensitivity to peer rejection and the increased risk of depression that occurs during adolescence.