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.

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.

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.

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.

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.

Although allostatic load has been investigated in mood and anxiety disorders, no prior study has investigated developmental change in allostatic load as a precursor to schizotypal personality. This study employed a multilevel developmental framework to examine whether the development of increased allostatic load, as indicated by impaired sympathetic nervous system habituation from ages 3 to 11 years, predisposes to schizotypal personality at age 23 years. Electrodermal activity to six aversive tones was recorded in 995 subjects at age 3 years and again at 11 years. Habituation slopes at both ages were used to create groups who showed a developmental increase in habituation (decreased allostatic load), and those who showed a developmental decrease in habituation (increased allostatic load). Children who showed a developmental increase in allostatic load from ages 3 to 11 years had higher levels of schizotypal personality at 23 years. A breakdown of total schizotypy scores demonstrated specificity of findings to cognitive–perceptual features of schizotypy. Findings are the first to document a developmental abnormality in allostasis in relation to adult schizotypal personality. The relative failure to develop normal habituation to repeated stressors throughout childhood is hypothesized to result in an accumulation of allostatic load and consequently increased positive symptom schizotypy in adulthood.

Psychobiological models of allostatic load have delineated the effects of multiple processes that contribute to risk for psychopathology. This approach has been fruitful, but the interactive contributions of allostatic and environmental load remain understudied in early childhood. Because this developmental period encompasses the emergence of internalizing problems and biological sensitivity to early experiences, this is an important time to examine this process. In two studies, we examined allostatic and environmental load and links to subsequent internalizing and externalizing problems. Study 1 examined relations between load indices and maladjustment, concurrently and at multiple times between age 2 and kindergarten; Study 2 added more comprehensive risk indices in a sample following a group of highly fearful toddlers from 2 to 3 years of age. Results from both studies showed that increased allostatic load related to internalizing problems as environmental risk also increased. Study 2, in addition, showed that fearfulness interacted with allostatic and environmental load indices to predict greater anxiety among the fearful children who had high levels of allostatic and environmental load. Taken together, the findings support a model of risk for internalizing characterized by the interaction of biological and environmental stressors, and demonstrate the importance of considering individual differences and environmental context in applying models of allostatic load to developmental change in early childhood.

Using an ethnically diverse longitudinal sample of 338 kindergarten children, this study examined the effects of cumulative contextual stressors on children's developing hypothalamic–pituitary–adrenocortical (HPA) axis regulation as an early life indicator of allostatic load. Chronic HPA axis regulation was assessed using cumulative, multiday measures of cortisol in both the fall and spring seasons of the kindergarten year. Hierarchical linear regression analyses revealed that contextual stressors related to ethnic minority status, socioeconomic status, and family adversity each uniquely predicted children's daily HPA activity and that some of those associations were curvilinear in conformation. Results showed that the quadratic, U-shaped influences of family socioeconomic status and family adversity operate in different directions to predict children's HPA axis regulation. Results further suggested that these associations differ for White and ethnic minority children. In total, this study revealed that early childhood experiences contribute to shifts in one of the principal neurobiological systems thought to generate allostatic load, confirming the importance of early prevention and intervention efforts. Moreover, findings suggested that analyses of allostatic load and developmental theories accounting for its accrual would benefit from an inclusion of curvilinear associations in tested predictive models.

Child maltreatment and biomarkers of allostatic load were investigated in relation to child health problems and psychological symptomatology. Participants attended a summer research day camp and included 137 maltreated and 110 nonmaltreated low-income children, who were aged 8 to 10 years (M = 9.42) and racially and ethnically diverse; 52% were male. Measurements obtained included salivary cortisol and dehydroepiandosterone, body mass index, waist–hip ratio, and blood pressure; these indicators provided a composite index of allostatic load. Child self-report and camp adult-rater reports of child symptomatology were obtained; mothers provided information on health problems. The results indicated that higher allostatic load and child maltreatment status independently predicted poorer health outcomes and greater behavior problems. Moderation effects indicated that allostatic load was related to somatic complaints, attention problems, and thought problems only among maltreated children. Risks associated with high waist–hip ratio, low morning cortisol, and high morning dehydroepiandosterone also were related to depressive symptoms only for maltreated children. The results support an allostatic load conceptualization of the impact of high environmental stress and child abuse and neglect on child health and behavioral outcomes and have important implications for long-term physical and mental health.

Within an allostatic load framework, the effect of Gene × Environment (G × E) interactions on diurnal cortisol regulation and internalizing symptomatology were investigated. Variation in the corticotropin releasing hormone receptor 1 (CRHR1) TAT haplotype and serotonin transporter linked polymorphic region (5-HTTLPR) was determined in a sample of maltreated (n = 238, 21.4% with early physical and sexual abuse) and nonmaltreated (n = 255) children (M age = 10.08) participating in a summer research camp. Internalizing and depressive symptoms were assessed by other and self-report. G × E effects for CRHR1 and maltreatment and early abuse on diurnal cortisol regulation were observed; CRHR1 variation was related to cortisol dysregulation only among maltreated children. Early abuse and high internalizing symptoms also interacted to predict atypical diurnal cortisol regulation. The interaction of CRHR1, 5-HTTLPR, and child maltreatment (G × G × E) identified a subgroup of maltreated children with high internalizing symptoms who shared the same combination of the two genes. The findings support an allostatic load perspective on the effects of the chronic stress associated with child maltreatment on cortisol regulation and internalizing symptomatology as moderated by genetic variation.

Experimental animal studies and adult research consistently show that stress exposure and/or psychological symptoms are associated with poorer health and immune functioning. The application to children is not yet clear, however, and we lack developmental models for studies in this area. The objective of this paper was to test the hypothesis that self-reported self-efficacy and depression, two markers of psychological well-being in children, would predict immunity and rate of illnesses. The data are based on a prospective study of 141 healthy, normally developing children aged 7–13 years who were recruited from an ambulatory pediatric setting. Children completed self-efficacy and depression measures and had blood obtained for IL-6 plasma levels and natural killer cell functional assays on three occasions, 6 months apart. Parents maintained weekly child illness diaries over 1 year using a thermometer to record fever. Parent psychiatric symptoms and income were used as covariates. Results indicated that, across the three occasions of measurement collected over the 1-year period, higher perceived self-efficacy was significantly associated with lower plasma interleukin 6 concentrations. There was no overall main effect of depressive symptoms on immune measures; however, for older girls, higher depression was associated with elevated natural killer cell cytotoxicity and an increased rate of total illnesses and febrile illnesses. The findings provide some of the first evidence that psychological processes are associated with immunity and health in a normally developing sample of preadolescents. Furthermore, the pattern of results suggests a modified model of a link between psychological well-being and immunological processes in children. These results build on and expand research on the notion of allostatic load and develop a groundwork for developmental studies in this area.

Allostasis, or the maintenance of stability through physiological change, refers to the process by which individuals adjust to the continually changing demands that are put upon somatic activity by salient events. Bauer and colleagues proposed that allostasis could be detected through patterns of the joint reactivity of the autonomic nervous system (ANS) and hypothalamic–pituitary–adrenal (HPA) axis system under stressful conditions. We examined the associations between ANS and HPA reactivity and the development of externalizing and internalizing problems over 2 years in a sample of 215 adolescents. The interactions of ANS and HPA reactivity were contemporaneously associated with, and longitudinally predictive of, adolescents' emotional and behavioral problems. Adolescents with symmetrical high reactivity across systems had more internalizing and fewer externalizing problems initially. Over time, both symmetrical and asymmetrical reactivity predicted increasing internalizing problems in girls, depending on the measure of ANS activity that was examined, heart rate, or blood pressure reactivity. Implications for the understanding of allostasis and the dynamic nature of the relations between multiple physiological regulatory systems and adolescents' developing psychopathology are discussed.

The concept of allostasis suggests that greater cumulative stress burden can influence stress-responsive physiology. Dysregulation of allostatic mediators, including the hypothalamic–pituitary–adrenal (HPA) axis, is thought to precede many other signs of age-related pathology as the persistent burden of stressors accumulates over the individual's life span. We predicted that even in young adulthood, HPA regulation would differ between Blacks and Whites, reflecting, in part, higher rates of stressor exposure and greater potential for stressors to “get under the skin.” We examined whether stressor exposure, including experiences with racism and discrimination, explained race differences in waking cortisol and the diurnal rhythm. We also examined whether HPA functioning was associated with mental health outcomes previously linked to cortisol. Salivary cortisol was assayed in 275 young adults (127 Blacks, 148 Whites, 19 to 22 years old), four times a day across 3 days. Hierarchical linear models revealed flatter slopes for Blacks, reflecting significantly lower waking and higher bedtime cortisol levels compared to Whites. Associations of HPA functioning with stressors were typically more robust for Whites such that more stress exposure created an HPA profile that resembled that of Black young adults. For Blacks, greater stressor exposure did not further impact HPA functioning, or, when significant, was often associated with higher cortisol levels. Across both races, flatter slopes generally indicated greater HPA dysregulation and were associated with poor mental health outcomes. These differential effects were more robust for Whites. These findings support an allostatic model in which social contextual factors influence normal biorhythms, even as early as young adulthood.

Allostatic load is the “wear and tear” of the body resulting from the repeated activation of compensatory physiological mechanisms in response to chronic stress. Allostatic load can significantly affect the aging process and result in reduced longevity, accelerated aging, and impaired health. Although low socioeconomic status is associated with high allostatic load during aging, the effects of status-related psychosocial stress on allostatic load are often confounded by lifestyle variables. Chronic psychosocial stress associated with low dominance rank in nonhuman primates represents an excellent animal model with which to investigate allostatic load and aging in humans. Research conducted with free-ranging rhesus monkeys suggests that female reproduction can also be a source of stress and allostatic load. Female reproduction is associated with increased risk of mortality and hyperactivation of the hypothalamic–pituitary–adrenal axis. Reproduction is especially stressful and costly for aging females of low rank. Although many indicators of body condition and neuroendocrine and immune function are influenced by aging, there are marked and stable individual differences among aging females in body condition, plasma cortisol responses to stress, and cytokine responses to stress. These differences are consistent with the hypothesis that there are strong differences in chronic stress among individuals, and that allostatic load resulting from chronic stress affects health during aging. Comparisons between captive and free-ranging rhesus monkey populations may allow us to understand how differences in environmental stress and allostatic load affect rates of aging, and how these in turn translate into differences in longevity and health.