This Special Issue of Development and Psychopathology is devoted to the psychological and biological consequences of stress across the developmental course. Contributions in this Special Issue address topics that are central to elucidating the impact that stress exerts on developmental outcomes. These issues are investigated through examining a diverse array of populations, including rodent and nonhuman primate samples, as well as cohorts of maltreated children and adolescents with and without posttraumatic stress disorder (PTSD), children who were adopted from Romanian orphanages at differing points during infancy, aging Holocaust survivors and their offspring, children with depressive disorder, adolescents with schizotypal personality disorder, and adults with bipolar and unipolar mood disorders.

Increasing evidence supports the view that the interaction of perinatal exposure to adversity with individual genetic liabilities may increase an individual's vulnerability to the expression of psycho- and physiopathology throughout life. The early environment appears to program some aspects of neurobiological development and, in turn, behavioral, emotional, cognitive, and physiological development. Several rodent and primate models of early adverse experience have been analyzed in this review, including those that “model” maternal separation or loss, abuse or neglect, and social deprivation. Accumulating evidence shows that these early traumatic experiences are associated with long-term alterations in coping style, emotional and behavioral regulation, neuroendocrine responsiveness to stress, social “fitness,” cognitive function, brain morphology, neurochemistry, and expression levels of central nervous system genes that have been related to anxiety and mood disorders. Studies are underway to identify important aspects of adverse early experience, such as (a) the existence of “sensitive periods” during development associated with alterations in particular output systems, (b) the presence of “windows of opportunity” during which targeted interventions (e.g., nurturant parenting or supportive–enriching environment) may prevent or reverse dysfunction, (c) the identity of gene polymorphisms contributing to the individual's variability in vulnerability, and (d) a means to translate the timing of these developmental “sensitive periods” across species.

Child abuse is associated with markedly elevated rates of major depression (MDD) in child, adolescent, and adult cohorts. This article reviews preclinical (e.g., animal) studies of the effects of early stress and studies of the neurobiological correlates of MDD in adults and children, and it highlights differences in the neurobiological correlates of MDD and stress at various developmental stages. The preclinical studies demonstrate that stress early in life can alter the development multiple neurotransmitter systems and promote structural and functional alterations in brain regions similar to those seen in adults with depression. Preclinical and clinical studies suggest, however, that long-term neurobiological changes associated with early stress can be modified by familial/genetic factors, the quality of the subsequent caregiving environment, and pharmacological interventions. Little is known about how developmental factors interact with experiences of early stress and these other modifying factors. Moreover, in cases of child maltreatment, the effects of early abuse are often exacerbated by failures in the child protection system and repeat out-of-home placements. Given the number of factors that impact on the long-term outcome of maltreated children, multidisciplinary research efforts are recommended to address this problem—with foci that span from neurobiology to social policy.

Childhood abuse is an important public health problem; however, little is known about the effects of abuse on the brain and neurobiological development. This article reviews the behavioral and biological consequences of childhood abuse and places them in a developmental context. Animal studies show that both positive and negative events early in life can influence neurobiological development in unique ways. Early stressors such as maternal separation result in lasting effects on stress-responsive neurobiological systems, including the hypothalamic–pituitary–adrenal (HPA) axis and noradrenergic systems. These studies also implicate a brain area involved in learning and memory, the hippocampus, in the long-term consequences of early stress. Clinical studies of patients with a history of abuse also implicate dysfunction in the HPA axis and the noradrenergic and hippocampal systems; however, there are multiple questions related to chronicity of stress, developmental epoch at the time of the stressor, presence of stress-related psychiatric disorders including posttraumatic stress disorder and depression, and psychological factors mediating the response to trauma that need to be addressed in this field of research. Understanding the effects of abuse on the development of the brain and neurobiology will nevertheless have important treatment and policy implications.

Glucocorticoids (GCs), produced by the stress-responsive hypothalamic–pituitary–adrenal axis, are well recognized for their regulatory role in peripheral metabolism. GCs are also known to regulate various brain functions, with well-described effects on human cognition. Increased GC exposure in humans—including exposure to the endogenous GC, cortisol—at levels associated with stress, decreases memory and learning function. These results extend evidence from in vitro studies of synaptic and cell function and evidence from animals indicating the GCs can regulate substrates of memory function. While considerable evidence details these effects in adult humans and animals, relatively less is know about the effect of GCs on cognitive function in children and older adults. Investigators have suggested that children, particularly preschool-aged children, may be vulnerable to adverse consequences of increased GC secretion resulting from stress and neuropsychiatric diseases such as depression. Adverse GC effects on memory substrates and memory function in the adult have also fostered concern that age-related changes, including changes in GC receptors and changes in circulating cortisol levels, could lead to age-related increases in the adverse effect of GCs on brain function. Investigators have reported an association between age-related increases in cortisol levels and age-related memory decline, but this association may or may not be due to a direct effect of cortisol on memory substrates. A number of possible treatment approaches to prevent or remediate adverse GC-induced effects are under development. In general, the use of safe and effective agents for blocking adverse GC effects on brain functions including memory may offer benefits to individuals suffering acute and chronic stressors and could prevent brain changes relevant to stress, aging, and stress-related neuropsychiatric diseases.

Since the work of Hans Selye, stress has been associated with increased activity of the limbic–hypothalamic– pituitary–adrenocortical (LHPA) axis. Recently, a number of studies in adults have shown that this neuroendocrine axis may be hyporesponsive in a number of stress-related states. Termed hypocortisolism, the paradoxical suppression of the LHPA axis under conditions of trauma and prolonged stress presently challenges basic concepts in stress research. Adverse conditions that produce elevated cortisol levels early in life are hypothesized to contribute to the development of hypocortisolism in adulthood. However, as reviewed in this paper, hypocortisolism also may be a common phenomenon early in human childhood. Although preliminary at this point, the ubiquity of these findings is striking. We argue that developmental studies are needed that help explicate the origins of low cortisol and to determine whether the development of hypocortisolism is, in fact, preceded by periods of frequent or chronic activation of the LHPA axis. We also argue that developmental researchers who incorporate measures of salivary cortisol into their studies of at-risk populations need to be aware of the hypocortisolism phenomenon. Lower than expected cortisol values should not necessarily be relegated to the file drawer because they contradict the central dogma that stress must be associated with elevations in cortisol. Lastly, we note that evidence of low cortisol under adverse early life conditions in humans adds to the importance of understanding the implications of hypocortisolism for health and development.

In this review, a developmental traumatology model of child maltreatment and the risk for the intergenerational cycle of abuse and neglect using a mental health or posttraumatic stress model was described. Published data were reviewed that support the hypothesis that the psychobiological sequelae of child maltreatment may be regarded as an environmentally induced complex developmental disorder. Data to support this view, including the descriptions of both psychobiological and brain maturation studies in maltreatment research, emphasizing the similarities and differences between children, adolescents, and adults, were reviewed. Many suggestions for important future psychobiological and brain maturation research investigations as well as public policy ideas were offered.

From a transactional developmental perspective, the authors review findings from studies of animals and humans regarding a proposed relation between stress system abnormalities and major depression. The stress system has evolved to promote successful adaptation across the life span, but disruptions in its functioning may increase the risk of pathological outcomes. Emphasis is placed on the role of prenatal and early postnatal experience in contributing to individual differences in postnatal stress reactivity, which may interact with cognitive and psychosocial vulnerabilities to increase susceptibility to later onset of depression. Findings regarding cognitive, psychosocial, and medical sequelae of depression are also reviewed, with a focus on the possible mediating role of the stress system. The authors highlight the importance of multidisciplinary, longitudinal studies in attempting to gain a deeper understanding of the complex developmental processes involved in the onset and course of depression.

Different types of psychosocial stressors have long been recognized as potential precipitants of both unipolar and bipolar affective episodes and the causative agents in posttraumatic stress disorder (PTSD). New preclinical data have revealed some of the neurobiological mechanisms that could convey the long-term behavioral and biochemical consequences of early stressors. Depending on the timing, quality, quantity, and degree of repetition, maternal deprivation stress in the neonatal rodent can be associated with lifelong anxiety-like behaviors, increases in stress hormones and peptides, and proneness to drug and alcohol administration, in association with acute changes in the rate of neurogenesis and apoptosis (preprogrammed cell death) and decrements in neurotrophic factors and signal transduction enzymes necessary for learning and memory. Patients with bipolar illness who have a history of early extreme adversity (physical or sexual abuse in childhood or adolescence), compared with those without, show an earlier onset of illness, faster cycling frequencies, increased suicidality, more Axis I and Axis II comorbidities (including alcohol and substance abuse), and more time ill in more than 2 years of prospective follow-up. These findings are subject to a variety of interpretations, but to the extent that the more severe course of bipolar illness characteristics are directly and causally related to these early stressful experiences, early recognition and treatment of high-risk children could be crucial in helping to prevent or ameliorate the long-term adverse consequences of these stressors.

The origins of individual differences in social development are examined in relation to early stress (immune challenge) and social milieu (maternal behavior) in a genetic–developmental analysis using an animal model. Neonatal male mice (5 or 6 days of age) from two lines of mice selectively bred for high versus low levels of inter-male aggressive behavior received a standard immune challenge (i.p. injections of 0.05 mg/kg endotoxin or saline). Animals were reared by their line-specific biological dam or by a foster dam from a line bred without selection. Adult levels of social behaviors were assessed in a dyadic test (age 45–50 days). Mice from the high-aggressive line show more developmental sensitivity to immune challenge than mice from the low-aggressive line, and line differences persist regardless of the early maternal environment. As adults, endotoxin-treated mice from the high-aggressive line have lower levels of aggressive behavior, longer latency to attack, and higher rates of socially reactive and inhibited behaviors compared to saline controls. Developmental effects of endotoxin in the low-aggressive line are minimal: endotoxin increases socially reactive behaviors, compared to saline controls, but only for mice reared by their biological dams. Rearing by foster dams increases social exploration in the low-aggressive line. The findings raise novel questions regarding the openness of behavioral systems to effects of nonobvious but omnipresent features of the environment, such as antigenic load, how these effects are integrated to affect social development and psychopathology, and the nature of intrinsic factors that contribute to individual differences in sensitivity to early stressors.

Six and a half years after adoption, 6- to 12-year-old children reared in Romanian orphanages for more than 8 months in their first years of life (RO, n = 18) had higher cortisol levels over the daytime hours than did early adopted (EA, ≤ 4 months of age, n = 15) and Canadian born (CB, n = 27) children. The effect was marked, with 22% of the RO children exhibiting cortisol levels averaged over the day that exceeded the mean plus 2 SD of the EA and CB levels. Furthermore, the longer beyond 8 months that the RO children remained institutionalized the higher their cortisol levels. Cortisol levels for EA children did not differ in any respect from those of CB comparison children. This latter finding reduces but does not eliminate concerns that the results could be due to prenatal effects or birth family characteristics associated with orphanage placement. Neither age at cortisol sampling nor low IQ measured earlier appeared to explain the findings. Because the conditions in Romanian orphanages at the time these children were adopted were characterized by multiple risk factors, including gross privation of basic needs and exposure to infectious agents, the factor(s) that produced the increase in cortisol production cannot be determined. Nor could we determine whether these results reflected effects on the limbic–hypothalamic–pituitary– adrenal axis directly or were mediated by differences in parent–child interactions or family stress occasion by behavioral problems associated with prolonged orphanage care in this sample.

The study was based on the assumption that stressors in the lives of pregnant and parenting women are processes that affect prenatal, postpartum, and concurrent maternal hormones and emotions and that these processes affect child temperament. The hypotheses were tested in a group of 67 young mothers and their 3-year-old children. Mothers were clustered into groups based on longitudinal patterns of hormones and emotions at prenatal, postpartum, and 3-year follow-up assessments. The analyses focused on relating maternal patterns of hormones and emotions to the child's temperament at age 3 years. Temperament was assessed by questionnaire and observation of behavior during a challenging situation. Illustrative findings included the following. Verbal aggression and nonverbal aggression were significantly higher in children of mothers in the low prenatal hormone cluster than children of mothers in the high prenatal hormone cluster. Children of mothers in the postpartum low testosterone (T), estradiol (E2), and androstenedione (Δ4-A) and medium cortisol (Cort) cluster (mainly low hormone cluster) exhibited significantly more physical aggression than children of mothers in the medium T and Δ4-A, high E2 and low Cort cluster. Maternal patterns of hormones, emotions, and parenting attitudes and practices were related to multiple aspects of temperament when the children were age 3 years. The findings support the important role of maternal biological and psychological processes in the development of child temperament.

It is well known that individuals from more advantaged social classes enjoy better mental and physical health than do individuals within lower classes. Various mechanisms have been evoked to explain the association between socioeconomic status (SES) and health. One mechanism that has received particular attention in recent years is stress. It has been shown that individuals lower in SES report greater exposure to stressful life events and a greater impact of these events on their life than individuals higher in SES. In order to measure whether the development of the relationship between SES and mental health is sustained by exposure to high levels of glucocorticoids, we measured morning salivary cortisol levels as well as cognitive function (memory, attention, and language) in 307 children (from 6 to 16 years of age) from low versus high SES in the Montreal area in Canada. The results revealed that low SES children from 6 to 10 years old present significantly higher salivary cortisol levels when compared to children from high SES. This difference disappears at the time of school transition, and no SES differences are observed in salivary cortisol levels during high school. However, children from low and high SES do not differ with regard to memory or to attentional and linguistic functions. Also, mothers of low SES children reported higher feelings of depression and more unhealthy behaviors, while mothers of high SES children reported higher stress related to work or family transitions. Altogether, these results show that low SES in young children is related to increased cortisol secretion, although the impact of SES on cortisol secretion is absent after transition to high school. These data are interpreted within the context of the equalization process of class patterning. Four social explanatory factors are suggested to explain the disappearance of SES differences in basal cortisol levels after school transition, taking into account the influence of family environment on the child's secretion of stress hormones.

Cortisol regulation was investigated in a sample of school-aged maltreated (n = 175) and demographically comparable low-income nonmaltreated (n = 209) children in the context of a day camp research program. Overall group differences between maltreated and nonmaltreated children were not found for average morning or average afternoon cortisol levels. However, significant variations were found that were based on the subtypes of maltreatment that the children had experienced. Maltreated children who had been both physically and sexually abused (as well as neglected or emotionally maltreated) exhibited substantial elevations in morning cortisol levels; children who had high (>1 SD) cortisol levels in both the morning and afternoon were also overrepresented in the multiple abuse group. Developmental timing of maltreatment did not account for these group differences, whereas the severity of sexual abuse was implicated. In contrast to the multiple abuse group, a subgroup of physically abused children showed evidence of a trend toward lower morning cortisol relative to nonmaltreated children with a significantly smaller decrease in cortisol levels from morning to afternoon. The findings are discussed in terms of the diversity of atypical cortisol regulation patterns that are exhibited among maltreated children.

The purpose of this study was to examine adrenocortical activity (basal, diurnal variation, and responses to social stressors) in adolescents at risk for psychopathology. Salivary cortisol levels were examined in normally developing and at-risk youth with internalizing and externalizing symptoms ranging from subclinical to clinical levels. Adolescents showed expected patterns of diurnal variation, with high early morning cortisol levels and a pattern of decline throughout the day. Females showed higher midday and late afternoon levels than males, and these patterns interacted with risk status. Internalizing problems sometimes were associated with gradual rather than steep declines in basal cortisol production. Both immediate and delayed cortisol reactivity to a social performance stressor were associated with internalizing symptoms. There was no evidence of relations between externalizing problems and underarousal of the hypothalamic–pituitary–adrenal (HPA) system. These and other results suggest that gender is an important moderating factor linking psychopathology, development, and context with HPA axis functioning in adolescence.

Adolescence is associated with an increase in the rate of certain psychiatric symptoms, and it is typically the developmental period when prodromal features of the major psychiatric disorders emerge. This is especially true of schizophrenia, with the majority of patients showing a marked postpubertal rise in schizotypal signs that predates the onset of clinical symptoms in early adulthood. Cross-sectional studies of youth have revealed a positive correlation between age and saliva cortisol level, suggesting a normative maturational increase in activity of the hypothalamic–pituitary–adrenal (HPA) axis. It has been hypothesized that this increase may trigger the expression of symptoms in vulnerable individuals. The present longitudinal study measured cortisol secretion and its relation with symptom development in samples of youth with schizotypal personality disorder (SPD), other personality disorders, or no Axis II disorder. The findings indicate moderate stability in cortisol levels across a 2-year period, with a longitudinal increase in cortisol levels over time. Cortisol levels at the first and second assessments were correlated with the severity of SPD symptoms at follow-up. The results are consistent with the notion that the HPA axis undergoes a postpubertal maturational process that moderates the expression of psychiatric symptoms.

Among the adverse mental health consequences of childhood trauma is the risk related to the development of posttraumatic stress disorder (PTSD) in adulthood. Other risk factors for PTSD, including parental trauma exposure and parental PTSD, can also contribute to the experience of child trauma. We examined associations between childhood trauma and PTSD in 51 adult children of Holocaust survivors and 41 comparison subjects, in consideration of parental trauma exposure and parental PTSD. We also examined these variables in relation to 24-hr urinary cortisol levels. Adult offspring of Holocaust survivors showed significantly higher levels of self-reported childhood trauma, particularly emotional abuse and neglect, relative to comparison subjects. The difference was largely attributable to parental PTSD. Self-reported childhood trauma was also related to severity of PTSD in subjects, and emotional abuse was significantly associated with 24-hr mean urinary cortisol secretion. We conclude that the experience of childhood trauma may be an important factor in the transmission of PTSD from parent to child.