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

Increasing evidence supports the view that the interaction of perinatal exposure to adversitywith individual genetic liabilities may increase an individual's vulnerability to the expressionof psycho- and physiopathology throughout life. The early environment appears to program someaspects of neurobiological development and, in turn, behavioral, emotional, cognitive, andphysiological development. Several rodent and primate models of early adverse experience havebeen analyzed in this review, including those that “model” maternal separation orloss, abuse or neglect, and social deprivation. Accumulating evidence shows that these earlytraumatic experiences are associated with long-term alterations in coping style, emotional andbehavioral regulation, neuroendocrine responsiveness to stress, social “fitness,”cognitive function, brain morphology, neurochemistry, and expression levels of central nervoussystem genes that have been related to anxiety and mood disorders. Studies are underway toidentify important aspects of adverse early experience, such as (a) the existence of“sensitive periods” during development associated with alterations in particularoutput systems, (b) the presence of “windows of opportunity” during whichtargeted interventions (e.g., nurturant parenting or supportive–enriching environment) mayprevent or reverse dysfunction, (c) the identity of gene polymorphisms contributing to theindividual's variability in vulnerability, and (d) a means to translate the timing of thesedevelopmental “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 effectsof early stress and studies of the neurobiological correlates of MDD in adults and children, and ithighlights differences in the neurobiological correlates of MDD and stress at variousdevelopmental stages. The preclinical studies demonstrate that stress early in life can alter thedevelopment multiple neurotransmitter systems and promote structural and functional alterationsin brain regions similar to those seen in adults with depression. Preclinical and clinical studiessuggest, however, that long-term neurobiological changes associated with early stress can bemodified by familial/genetic factors, the quality of the subsequent caregiving environment,and pharmacological interventions. Little is known about how developmental factors interact withexperiences of early stress and these other modifying factors. Moreover, in cases of childmaltreatment, the effects of early abuse are often exacerbated by failures in the child protectionsystem and repeat out-of-home placements. Given the number of factors that impact on thelong-term outcome of maltreated children, multidisciplinary research efforts are recommended toaddress this problem—with foci that span from neurobiology to social policy.

Childhood abuse is an important public health problem; however, little is known about theeffects of abuse on the brain and neurobiological development. This article reviews the behavioraland 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 influenceneurobiological development in unique ways. Early stressors such as maternal separation result inlasting effects on stress-responsive neurobiological systems, including thehypothalamic–pituitary–adrenal (HPA) axis and noradrenergic systems. Thesestudies also implicate a brain area involved in learning and memory, the hippocampus, in thelong-term consequences of early stress. Clinical studies of patients with a history of abuse alsoimplicate 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 thestressor, presence of stress-related psychiatric disorders including posttraumatic stress disorderand depression, and psychological factors mediating the response to trauma that need to beaddressed in this field of research. Understanding the effects of abuse on the development of thebrain and neurobiology will nevertheless have important treatment and policy implications.

Glucocorticoids (GCs), produced by the stress-responsivehypothalamic–pituitary–adrenal axis, are well recognized for their regulatory role inperipheral metabolism. GCs are also known to regulate various brain functions, withwell-described effects on human cognition. Increased GC exposure in humans—includingexposure to the endogenous GC, cortisol—at levels associated with stress, decreasesmemory and learning function. These results extend evidence from in vitro studies of synaptic andcell function and evidence from animals indicating the GCs can regulate substrates of memoryfunction. While considerable evidence details these effects in adult humans and animals, relativelyless 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 bevulnerable to adverse consequences of increased GC secretion resulting from stress andneuropsychiatric diseases such as depression. Adverse GC effects on memory substrates andmemory function in the adult have also fostered concern that age-related changes, includingchanges in GC receptors and changes in circulating cortisol levels, could lead to age-relatedincreases in the adverse effect of GCs on brain function. Investigators have reported anassociation between age-related increases in cortisol levels and age-related memory decline, butthis association may or may not be due to a direct effect of cortisol on memory substrates. Anumber of possible treatment approaches to prevent or remediate adverse GC-induced effects areunder development. In general, the use of safe and effective agents for blocking adverse GCeffects on brain functions including memory may offer benefits to individuals suffering acute andchronic stressors and could prevent brain changes relevant to stress, aging, and stress-relatedneuropsychiatric diseases.

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

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

From a transactional developmental perspective, the authors review findings from studies ofanimals and humans regarding a proposed relation between stress system abnormalities and majordepression. 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 isplaced on the role of prenatal and early postnatal experience in contributing to individualdifferences in postnatal stress reactivity, which may interact with cognitive and psychosocialvulnerabilities 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 possiblemediating role of the stress system. The authors highlight the importance of multidisciplinary,longitudinal studies in attempting to gain a deeper understanding of the complex developmentalprocesses involved in the onset and course of depression.

Different types of psychosocial stressors have long been recognized as potential precipitantsof both unipolar and bipolar affective episodes and the causative agents in posttraumatic stressdisorder (PTSD). New preclinical data have revealed some of the neurobiological mechanismsthat 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 inthe neonatal rodent can be associated with lifelong anxiety-like behaviors, increases in stresshormones and peptides, and proneness to drug and alcohol administration, in association withacute changes in the rate of neurogenesis and apoptosis (preprogrammed cell death) anddecrements in neurotrophic factors and signal transduction enzymes necessary for learning andmemory. Patients with bipolar illness who have a history of early extreme adversity (physical orsexual abuse in childhood or adolescence), compared with those without, show an earlier onset ofillness, 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 prospectivefollow-up. These findings are subject to a variety of interpretations, but to the extent that themore severe course of bipolar illness characteristics are directly and causally related to these earlystressful experiences, early recognition and treatment of high-risk children could be crucial inhelping 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 earlystress (immune challenge) and social milieu (maternal behavior) in a genetic–developmentalanalysis using an animal model. Neonatal male mice (5 or 6 days of age) from two lines of miceselectively bred for high versus low levels of inter-male aggressive behavior received a standardimmune challenge (i.p. injections of 0.05 mg/kg endotoxin or saline). Animals were reared bytheir line-specific biological dam or by a foster dam from a line bred without selection. Adultlevels of social behaviors were assessed in a dyadic test (age 45–50 days). Mice from thehigh-aggressive line show more developmental sensitivity to immune challenge than mice from thelow-aggressive line, and line differences persist regardless of the early maternal environment. Asadults, endotoxin-treated mice from the high-aggressive line have lower levels of aggressivebehavior, longer latency to attack, and higher rates of socially reactive and inhibited behaviorscompared to saline controls. Developmental effects of endotoxin in the low-aggressive line areminimal: endotoxin increases socially reactive behaviors, compared to saline controls, but only formice reared by their biological dams. Rearing by foster dams increases social exploration in thelow-aggressive line. The findings raise novel questions regarding the openness of behavioralsystems to effects of nonobvious but omnipresent features of the environment, such as antigenicload, how these effects are integrated to affect social development and psychopathology, and thenature 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 orphanagesfor more than 8 months in their first years of life (RO, n = 18) had higher cortisollevels 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 theRO 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 parentingwomen are processes that affect prenatal, postpartum, and concurrent maternal hormones andemotions and that these processes affect child temperament. The hypotheses were tested in agroup of 67 young mothers and their 3-year-old children. Mothers were clustered into groupsbased on longitudinal patterns of hormones and emotions at prenatal, postpartum, and 3-yearfollow-up assessments. The analyses focused on relating maternal patterns of hormones andemotions to the child's temperament at age 3 years. Temperament was assessed byquestionnaire and observation of behavior during a challenging situation. Illustrative findingsincluded the following. Verbal aggression and nonverbal aggression were significantly higher inchildren of mothers in the low prenatal hormone cluster than children of mothers in thehigh 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 andphysical health than do individuals within lower classes. Various mechanisms have been evoked toexplain the association between socioeconomic status (SES) and health. One mechanism that hasreceived particular attention in recent years is stress. It has been shown that individuals lower inSES report greater exposure to stressful life events and a greater impact of these events on theirlife than individuals higher in SES. In order to measure whether the development of therelationship between SES and mental health is sustained by exposure to high levels ofglucocorticoids, 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 versushigh SES in the Montreal area in Canada. The results revealed that low SES children from 6 to 10years old present significantly higher salivary cortisol levels when compared to children from highSES. This difference disappears at the time of school transition, and no SES differences areobserved in salivary cortisol levels during high school. However, children from low and high SESdo not differ with regard to memory or to attentional and linguistic functions. Also, mothers oflow SES children reported higher feelings of depression and more unhealthy behaviors, whilemothers 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 cortisolsecretion, although the impact of SES on cortisol secretion is absent after transition to highschool. These data are interpreted within the context of the equalization process of classpatterning. Four social explanatory factors are suggested to explain the disappearance of SESdifferences in basal cortisol levels after school transition, taking into account the influence offamily 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 inthe context of a day camp research program. Overall group differences between maltreated andnonmaltreated 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 thatthe children had experienced. Maltreated children who had been both physically and sexuallyabused (as well as neglected or emotionally maltreated) exhibited substantial elevations inmorning cortisol levels; children who had high (>1 SD) cortisol levels in both themorning and afternoon were also overrepresented in the multiple abuse group. Developmentaltiming of maltreatment did not account for these group differences, whereas the severity of sexualabuse was implicated. In contrast to the multiple abuse group, a subgroup of physically abusedchildren showed evidence of a trend toward lower morning cortisol relative to nonmaltreatedchildren with a significantly smaller decrease in cortisol levels from morning to afternoon. Thefindings are discussed in terms of the diversity of atypical cortisol regulation patterns that areexhibited among maltreated children.

The purpose of this study was to examine adrenocortical activity (basal, diurnal variation, andresponses to social stressors) in adolescents at risk for psychopathology. Salivary cortisol levelswere examined in normally developing and at-risk youth with internalizing and externalizingsymptoms ranging from subclinical to clinical levels. Adolescents showed expected patterns ofdiurnal variation, with high early morning cortisol levels and a pattern of decline throughout theday. Females showed higher midday and late afternoon levels than males, and these patternsinteracted with risk status. Internalizing problems sometimes were associated with gradual ratherthan steep declines in basal cortisol production. Both immediate and delayed cortisol reactivity toa social performance stressor were associated with internalizing symptoms. There was noevidence of relations between externalizing problems and underarousal of thehypothalamic–pituitary–adrenal (HPA) system. These and other results suggest thatgender is an important moderating factor linking psychopathology, development, and context withHPA axis functioning in adolescence.

Adolescence is associated with an increase in the rate of certain psychiatric symptoms, and itis typically the developmental period when prodromal features of the major psychiatric disordersemerge. This is especially true of schizophrenia, with the majority of patients showing a markedpostpubertal rise in schizotypal signs that predates the onset of clinical symptoms in earlyadulthood. Cross-sectional studies of youth have revealed a positive correlation between age andsaliva cortisol level, suggesting a normative maturational increase in activity of thehypothalamic–pituitary–adrenal (HPA) axis. It has been hypothesized that thisincrease may trigger the expression of symptoms in vulnerable individuals. The presentlongitudinal study measured cortisol secretion and its relation with symptom development insamples of youth with schizotypal personality disorder (SPD), other personality disorders, or noAxis 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 secondassessments were correlated with the severity of SPD symptoms at follow-up. The results areconsistent with the notion that the HPA axis undergoes a postpubertal maturational process thatmoderates the expression of psychiatric symptoms.

Among the adverse mental health consequences of childhood trauma is the risk related to thedevelopment 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 ofchild trauma. We examined associations between childhood trauma and PTSD in 51 adult childrenof Holocaust survivors and 41 comparison subjects, in consideration of parental trauma exposureand 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-reportedchildhood trauma, particularly emotional abuse and neglect, relative to comparison subjects. Thedifference was largely attributable to parental PTSD. Self-reported childhood trauma was alsorelated to severity of PTSD in subjects, and emotional abuse was significantly associated with24-hr mean urinary cortisol secretion. We conclude that the experience of childhood trauma maybe an important factor in the transmission of PTSD from parent to child.