We previously used the theory of allostasis as the foundation for a model of the current stress process. This work highlighted the core emotional systems of the brain as the central mediator of the relationship between stress and health. In this paper, we extend this theoretical approach to consider the role of developmental timing. In doing so, we note that there are strong implicit models that underlie current developmental stress research in the social and life sciences. We endeavor to illustrate these models explicitly as we review the evidence behind each one and discuss their implications. We then extend these models to reflect recent findings from research in life span human neuroscience. The result is a new set of developmental allostatic models that provide fodder for future empirical research, as well as novel perspectives on intervention.

This investigation examined the extent to which polymorphisms of the serotonin transporter linked promoter region (5-HTTLPR) and the dopamine receptor D4 (DRD4) genes differentially influenced the development of attachment security and disorganization in maltreated and nonmaltreated infants at age 13 months, and the extent to which the efficacy of preventive interventions to promote attachment security were influenced by genetic variation. The sample consisted of 106 infants from maltreating families, participating in a randomized control trial evaluating the efficacy of two interventions, child–parent psychotherapy and psychoeducational parenting intervention, and 47 infants from nonmaltreating families. DNA samples were genotyped for polymorphisms of 5-HTTLPR, DRD4 exon III variable number tandem repeat, and DRD4-521. Attachment organization at age 1 and at age 2 was assessed with the Strange Situation for all participants, prior to and following the completion of the interventions. High rates of disorganized attachment were observed in the maltreatment compared to the nonmaltreatment group, and both interventions resulted in increased rates of attachment security at age 2. Genetic variation did not influence improvement in attachment organization among maltreated infants. Among maltreated infants, genetic variation had minimal effect on attachment organization. In contrast, among nonmaltreated infants, 5-HTTLPR and DRD4 polymorphisms influenced attachment security and disorganization at age 2 and the stability of attachment disorganization over time.

The allostatic load (AL) model represents an interdisciplinary approach to comprehensively conceptualize and quantify chronic stress in relation to pathologies throughout the life cycle. This article first reviews the AL model, followed by interactions among early adversity, genetics, environmental toxins, as well as distinctions among sex, gender, and sex hormones as integral antecedents of AL. We next explore perspectives on severe mental illness, dementia, and caregiving as unique human models of AL that merit future investigations in the field of developmental psychopathology. A complimenting transdisciplinary perspective is applied throughout, whereby we argue that the AL model goes beyond traditional stress–disease theories toward the advancement of person-centered research and practice that promote not only physical health but also mental health.

The term allostasis, which is defined as stability through change, has been invoked repeatedly by developmental psychopathologists to describe long-lasting and in some cases permanent functional alterations in limbic–hypothalamic–pituitary–adrenal axis responding following recurrent and/or prolonged exposure to stress. Increasingly, allostatic load models have also been invoked to describe psychological sequelae of abuse, neglect, and other forms of maltreatment. In contrast, neural adaptations to stress, including those incurred by monoamine systems implicated in (a) mood and emotion regulation, (b) behavioral approach, and (c) social affiliation and attachment, are usually not included in models of allostasis. Rather, structural and functional alterations in these systems, which are exquisitely sensitive to prolonged stress exposure, are usually explained as stress mediators, neural plasticity, and/or programming effects. Considering these mechanisms as distinct from allostasis is somewhat artificial given overlapping functions and intricate coregulation of monoamines and the limbic–hypothalamic–pituitary–adrenal axis. It also fractionates literatures that should be mutually informative. In this article, we describe structural and functional alterations in serotonergic, dopaminergic, and noradrenergic neural systems following both acute and prolonged exposure to stress. Through increases in behavioral impulsivity, trait anxiety, mood and emotion dysregulation, and asociality, alterations in monoamine functioning have profound effects on personality, attachment relationships, and the emergence of psychopathology.

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.

This study employed event-related potentials (ERPs) to investigate the neural correlates of facial affect processing in maltreated and nonmaltreated children at 42 months of age. ERPs elicited while children passively viewed standardized pictures of female models posing angry, happy, and neutral facial expressions were examined, and differences between maltreated (N = 46) and nonmaltreated (N = 25) children were reported. Three occipital components (P1, N170, and P400) and four frontal–central components (N150, P240, Nc, and a positive slow wave [PSW]) were identified. Findings revealed that maltreated children had greater P1 and P400 amplitude in response to angry facial affect compared to other emotions, and compared to nonmaltreated children. N170 amplitude was greater in response to happy compared to angry in the maltreated group. For the P240 component, maltreated children had greater amplitude in response to angry facial expressions relative to happy, whereas children in the nonmaltreated group had greater P240 amplitude in response to happy relative to angry facial affect. Further, the nonmaltreated group had greater PSW amplitude in response to angry facial affect, whereas those in the maltreated group showed greater PSW amplitude to happy facial expressions. The results provided further support for the hypothesis that the experience of maltreatment and the predominantly negative emotional tone in maltreating families alters the functioning of neural systems associated with the identification and processing of facial emotion. These results exemplify the importance of early preventive interventions focused on emotion for children who have experienced maltreatment early in life.

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.

The negative effects of prenatal substance exposure on neurobiological and psychological development and of early adversity are clear, but little is known about their combined effects. In this study, multilevel analyses of the effects of prenatal substance exposure and early adversity on the emergence of neurobehavioral disinhibition in adolescence were conducted. Neurobehavioral disinhibition has previously been observed to occur frequently in multiproblem youth from high-risk backgrounds. In the present study, neurobehavioral disinhibition was assessed via behavioral dysregulation and poor executive function composite measures. Data were drawn from a prospective longitudinal investigation of prenatal substance exposure that included 1,073 participants followed from birth through adolescence. The results from latent growth modeling analyses showed mean stability but significant individual differences in behavioral dysregulation and mean decline with individual differences in executive function difficulties. Prior behavioral dysregulation predicted increased executive function difficulties. Prenatal drug use predicted the emergence and growth in neurobehavioral disinhibition across adolescence (directly for behavioral dysregulation and indirectly for executive function difficulties via early adversity and behavioral dysregulation). Prenatal drug use and early adversity exhibited unique effects on growth in behavioral dysregulation; early adversity uniquely predicted executive function difficulties. These results are discussed in terms of implications for theory development, social policy, and prevention science.

The mechanisms through which early life stress leads to psychopathology are thought to involve allostatic load, the “wear and tear” an organism is subjected to as a consequence of sustained elevated levels of glucocorticoids caused by repeated/prolonged stress activations. The allostatic load model described this phenomenon, but has been criticized as inadequate to explain alterations associated with early adverse experience in some systems, including behavior, which cannot be entirely explained from an energy balance perspective. The reactive scope model has been more recently proposed and focuses less on energy balance and more on dynamic ranges of physiological and behavioral mediators. In this review we examine the mechanisms underlying the behavioral consequences of early life stress in the context of both these models. We focus on adverse experiences that involve mother–infant relationship disruption, and dissect those mechanisms involving maternal care as a regulator of development of neural circuits that control emotional and social behaviors in the offspring. We also discuss the evolutionary purpose of the plasticity in behavioral development, which has a clear adaptive value in a changing environment.

Longitudinal effects of child maltreatment on cortisol regulation in infants from age 1 to 3 years were investigated in the context of a randomized preventive intervention trial. Thirteen-month-old infants from maltreating families (N = 91) and their mothers were randomly assigned to one of three intervention conditions: child–parent psychotherapy, psychoeducational parenting intervention, and a control group involving standard community services (CS). A fourth group of infants from nonmaltreating families (N = 52) and their mothers comprised a nonmaltreated comparison (NC) group. The two active interventions were combined into one maltreated intervention (MI) group for statistical analyses. Saliva samples were obtained from children at 10:00 a.m. before beginning a laboratory observation session with their mothers when the children were 13 months of age (preintervention), 19 months (midintervention), 26 months (postintervention), and 38 months (1-year postintervention follow-up). At the initial assessment, no significant differences among groups in morning cortisol were observed. Latent growth curve analyses examined trajectories of cortisol regulation over time. Beginning at midintervention, divergence was found among the groups. Whereas the MI group remained indistinguishable from the NC group across time, the CS group progressively evinced lower levels of morning cortisol, statistically differing from the MI and NC groups. Results highlight the value of psychosocial interventions for early child maltreatment in normalizing biological regulatory processes.

Children in the birth to 5 age range are disproportionately exposed to traumatic events relative to older children, but they are underrepresented in the trauma research literature as well as in the development and implementation of effective clinical treatments and in public policy initiatives to protect maltreated children. Children from ethnic minority groups and those living in poverty are particularly affected. This paper discusses the urgent need to address the needs of traumatized young children and their families through systematic research, clinical, and public policy initiatives, with specific attention to underserved groups. The paper reviews research findings on early childhood maltreatment and trauma, including the role of parental functioning, the intergenerational transmission of trauma and psychopathology, and protective contextual factors in young children's response to trauma exposure. We describe the therapeutic usefulness of a simultaneous treatment focus on current traumatic experiences and on the intergenerational transmission of relational patterns from parent to child. We conclude with a discussion of the implications of current knowledge about trauma exposure for clinical practice and public policy and with recommendations for future research.

Childhood adversity is associated with increased risk for onset of depressive episodes. This review will present evidence that allostatic overload of the hypothalamic–pituitary–adrenal axis (HPAA) partially mediates this association. The HPAA is the physiological system that regulates levels of the stress hormone cortisol. First, data from animals and humans has shown that early environmental adversity is associated with long-term dysregulation of the HPAA. This may occur due to permanent epigenetic modification of the glucocorticoid receptor. Second, data from humans has demonstrated that HPAA dysregulation is associated with increased risk of future depression onset in healthy individuals, and pharmacological correction of HPAA dysregulation reduces depressive symptoms. HPAA dysregulation may result in corticoid-mediated abnormalities in neurogenesis in early life and/or neurotoxicity on neural systems that subserve emotion and cognition.

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.

Children's trauma-related mental health problems are widespread, largely untreated and constitute significant barriers to academic achievement and attainment. Translational research has begun to identify school-based interventions to prevent violence, trauma and psychopathology. We describe in detail the findings to date on research evaluating one such intervention, the Reading, Writing, Respect, and Resolution (4Rs) Program. The 4Rs Program has led to modest positive impacts on both classrooms and children after 1 year that appear to cascade to more impacts in other domains of children's development after 2 years. This research strives not only to translate research into practice but also translate practice into research. However, considerable challenges must be met for such research to inform prevention strategies at population scale.

Guided by an evolutionary model of allostatic load, this study examined the hypothesis that the association between interparental aggression and subsequent changes in children's cortisol reactivity to interparental conflict is moderated by their temperamental dispositions. Participants of the multimethod, longitudinal study included 201 2-year-old toddlers and their mothers. These children experienced elevated levels of aggression between parents. Consistent with the theory, the results indicated that interparental aggression predicted greater cortisol reactivity over a 1-year period for children who exhibited high levels of temperamental inhibition and vigilance. Conversely, for children with bold, aggressive temperamental characteristics, interparental aggression was marginally associated with diminished cortisol reactivity. Further underscoring its implications for allostatic load, increasing cortisol reactivity over the one year span was related to concomitant increases in internalizing symptoms but decreases in attention and hyperactivity difficulties. In supporting the evolutionary conceptualization, these results further supported the relative developmental advantages and costs associated with escalating and dampened cortisol reactivity to interparental conflict.

The hypothalamic–pituitary–adrenal (HPA) axis is a primary mechanism in the allostatic process through which early life stress (ELS) contributes to disease. Studies of the influence of ELS on children's HPA axis functioning have yielded inconsistent findings. To address this issue, the present study considers multiple types of ELS (maternal depression, paternal depression, and family expressed anger), mental health symptoms, and two components of HPA functioning (traitlike and epoch-specific activity) in a long-term prospective community study of 357 children. ELS was assessed during the infancy and preschool periods; mental health symptoms and cortisol were assessed at child ages 9, 11, 13, and 15 years. A three-level hierarchical linear model addressed questions regarding the influences of ELS on HPA functioning and its covariation with mental health symptoms. ELS influenced traitlike cortisol level and slope, with both hyper- and hypoarousal evident depending on type of ELS. Further, type(s) of ELS influenced covariation of epoch-specific HPA functioning and mental health symptoms, with a tighter coupling of HPA alterations with symptom severity among children exposed previously to ELS. Results highlight the importance of examining multiple types of ELS and dynamic HPA functioning in order to capture the allostatic process unfolding across the transition into adolescence.