Theory suggests that early experiences may calibrate the “threshold activity” of the hypothalamus–pituitary–adrenal axis in childhood. Particularly challenging or particularly supportive environments are posited to manifest in heightened physiological sensitivity to context. Using longitudinal data from the Family Life Project (N = 1,292), we tested whether links between maternal sensitivity and hypothalamus–pituitary–adrenal axis activity aligned with these predictions. Specifically, we tested whether the magnitude of the within-person relation between maternal sensitivity and children's cortisol levels, a proxy for physiological sensitivity to context, was especially pronounced for children who typically experienced particularly low or high levels of maternal sensitivity over time. Our results were consistent with these hypotheses. Between children, lower levels of mean maternal sensitivity (7–24 months) were associated with higher mean cortisol levels across this period (measured as a basal sample collected at each visit). However, the magnitude and direction of the within-person relation was contingent on children's average levels of maternal sensitivity over time. Increases in maternal sensitivity were associated with contemporaneous cortisol decreases for children with typically low-sensitive mothers, whereas sensitivity increases were associated with cortisol increases for children with typically high-sensitive mothers. No within-child effects were evident at moderate levels of maternal sensitivity.

This research explored sex differences in the pathways linking pubertal timing to depression across 4 years. A sample of 167 youth (M age = 12.41 years, SD = 1.19) and their caregivers completed measures of puberty and semistructured interviews of interpersonal stress and youth depression. Youth reported on psychological (negative self-focus, anxious arousal) and social–behavioral (coping) characteristics; parents reported on youths’ social–behavioral characteristics (withdrawal/social problems) and deviant peer affiliations. Early maturation predicted stable high trajectories of depression in girls; although early maturing boys showed low initial levels of depression, they did not differ from girls by the final wave of the study. Latent growth curve analyses identified several psychological, social–behavioral, and interpersonal pathways accounting for the contribution of pubertal timing to initial and enduring risk for depression in girls as well as emerging risk for depression in boys. These findings provide novel insight into multilevel processes accounting for sex differences in depression across the adolescent transition.

At multiple developmental periods spanning from middle childhood through adolescence, we investigated the development of aggressive-victims. Multiple-informant data collected across four grade levels (1, 5, 8, and 11; N = 482; 50% females) was used to perform person-centered analyses including latent profile and latent transition analyses in order to examine the co-occurring development of multiple forms (i.e., physical, verbal, and relational) of aggression and peer victimization. Results indicated that there were two distinct subgroups of aggressive-victims, one of which was more relational in form (i.e., relational aggressive-victims), and children in these two subgroups were distinguishable with respect to their individual characteristics (emotion dysregulation, withdrawn behaviors, and moral disengagement) and relational experiences (peer rejection and friendships). Furthermore, the findings elucidated the mechanisms by which developmental continuity and change (i.e., transitions) among the subgroups occurred across childhood and adolescence.

In a previous paper, the authors found that impairment on the Wisconsin Card Sorting Test (WCST) in adolescence was predictive of bipolar disorder in young adulthood among offspring of mothers with bipolar illness. In the present study, the authors explore the contribution of maternal characteristics, beyond maternal mood disorder, to the prediction of offspring dysfunction on the WCST. Results showed that maternal bipolar disorder and maternal negativity were both predictive of impaired performance on the WCST during adolescence. The contribution of maternal negativity to offspring WCST impairment was not better explained by maternal personality disorder, mother's functional impairment, family loading for bipolar disorder, or offspring disruptive behavioral disturbance. Findings did not support a moderator model. However, support was found for a mediation model in which maternal negativity contributed to risk for offspring bipolar disorder through its negative association with apparent frontal lobe functioning, as measured by the WCST. Findings are discussed from the perspective of a vulnerability–stress model. In addition, the authors consider the possibility that maternal negativity and offspring impairment on the WCST may be reflective of a common heritable trait.The findings presented in this paper come from the doctoral dissertation of the first author, which was funded by an NIMH Intramural Research Training Award. The authors are enormously grateful to Anne Mayfield, without whom this project would not have been possible. We are deeply indebted to Ann S. Masten, W. Andrew Collins, L. Alan Sroufe, Monica Luciana, and Carrie Borchardt, who provided support and guidance throughout all stages of this project. We are also thankful to Robert Asarnow for his advice and encouragement, and to Roger E. Meyer and Daniel N. Klein for their comments on earlier drafts of this paper. In addition, we acknowledge the contributions of Gail Inoff-Germain, who administered diagnostic interviews and neuropsychological measures at adolescent follow-up; Rula B. Garside, who undertook the painstaking job of establishing interrater reliability; Erika Sundstrom, who devoted many hours to data organization and quality assurance; and Sara Avery Torvik and Patricia Kasdan, whose combined gifts of organization and warmth created a comfortable atmosphere for study participants. Finally, we thank the extraordinary research participants of the NIMH Childrearing Study, who have shown enormous bravery and dedication by sharing with us 23 years of their lives.

Childhood neglect has been cited as a risk factor for later substance abuse and criminal behavior. However, a large body of literature shows that a substantial percentage of neglected and abused individuals do not go on to abuse substances or engage in criminal behavior. The current study investigates whether a genetic variant (serotonin transporter linked polymorphic region [5-HTTLPR]) in the 5-hydroxytryptamine (5-HTT) gene moderates the effect of childhood neglect on alcohol use problems, marijuana use, and criminal behavior. Data from the National Longitudinal Study of Adolescent Health shows that 5-HTTLPR conditions the effect of neglect on marijuana use for females, but not for males. Findings also reveal a significant gene–environment correlation between 5-HTTLPR and neglect for females only. These results suggest that 5-HTTLPR is associated with an increased risk of neglect for females, and it also increases neglected females’ risk of abusing marijuana.

This paper introduces a new, clinical-developmental approach to research, theory and intervention. A line of research is described exploring the relationship between developmental organizations of meaning and symptom expression in adolescence. These cross-sectional and longitudinal studies demonstrate needed distinctions between self-complexity and self-maturity/integration—concepts that are described in the context of an overarching framework. In the final section of the paper, clinical methods are introduced for different adolescent developmental worlds and are exemplified with two cases.

Associations between prenatal maternal psychological distress and offspring developmental outcomes are well documented, yet relatively little research has examined links between maternal distress and development in utero, prior to postpartum influences. Fetal heart rate (FHR) parameters are established indices of central and autonomic nervous system maturation and function which demonstrate continuity with postnatal outcomes. This prospective, longitudinal study of 149 maternal–fetal pairs evaluated associations between prenatal maternal distress, FHR parameters, and dimensions of infant temperament. Women reported their symptoms of psychological distress at five prenatal visits, and FHR monitoring was conducted at the last three visits. Maternal report of infant temperament was collected at 3 and 6 months of age. Exposure to elevated prenatal maternal psychological distress was associated with higher late-gestation resting mean FHR (FHRM) among female but not male fetuses. Higher late-gestation FHRM was associated with lower infant orienting/regulation and with higher infant negative affectivity, and these associations did not differ by infant sex. A path analysis identified higher FHRM as one pathway by which elevated prenatal maternal distress was associated with lower orienting/regulation among female infants. Findings suggest that, for females, elevated maternal distress alters fetal development, with implications for postnatal function. Results also support the notion that, for both sexes, individual differences in regulation emerge prenatally and are maintained into infancy. Collectively, these findings underscore the utility of direct assessment of development in utero when examining if prenatal experiences are carried forward into postnatal life.

The National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) initiative aims to understand the mechanisms influencing psychopathology through a dimensional approach. Limited research thus far has considered potential racial/ethnic differences in RDoC constructs that are influenced by developmental and contextual processes. A growing body of research has demonstrated that racial trauma is a pervasive chronic stressor that impacts the health of Black Americans across the life course. In this review article, we examine the ways that an RDOC framework could allow us to better understand the biological embedding of racial trauma among Black Americans. We also specifically examine the Negative Valence System domain of RDoC to explore how racial trauma is informed by and can help expand our understanding of this domain. We end the review by providing some additional research considerations and future research directives in the area of racial trauma that build on the RDoC initiative.

The current study examined trajectories of maternal and paternal depression in the year following the birth of an infant sibling, and relations with family risk factors and firstborn children's internalizing and externalizing behavior problems. Latent class growth analysis was conducted on 231 families in a longitudinal investigation (prebirth and 1, 4, 8, and 12 months postbirth) and revealed four classes of families: both mother and father low in depressive symptoms (40.7%); mother high–father low (25.1%); father high–mother low (24.7%), and both mother and father high (9.5%). Families with both mothers and fathers high on depressive symptoms were higher on marital negativity, parenting stress, and children's internalizing and externalizing problems, and lower on marital positivity and parental efficacy than other classes. Children, parents, and marital relationships were more problematic in families with fathers higher on depressive symptoms than in families in which mothers were higher, indicating the significant role of paternal support for firstborn children undergoing the transition to siblinghood. Maternal and paternal depression covaried with an accumulation of family risks over time, no doubt increasing the likelihood of children's problematic adjustment after the birth of their infant sibling.

Maltreatment during development is associated with epigenetic changes to the genome. Enhancing caregiving may mitigate these effects. Attachment and Biobehavioral Catch-Up (ABC) is an intervention that has been shown to improve parent–child relationships and a variety of biological and behavioral outcomes among children that are involved in Child Protective Services. This preliminary study, using a small sample size, explored whether children who received ABC exhibit different methylation patterns than those who received a control intervention. The participants included 23 children aged 6–21 months who were randomized to receive ABC (n = 12) or a control intervention (n = 11). While the children displayed similar methylation patterns preintervention, DNA methylation varied between the ABC and control groups at 14,828 sites postintervention. Functional pathway analyses indicated that these differences were associated with gene pathways that are involved in cell signaling, metabolism, and neuronal development. This study is one of the first to explore parenting intervention effects on children's DNA methylation at the whole genome level in infancy. These preliminary findings provide a basis for hypothesis generation in further research with larger-scale studies regarding the malleability of epigenetic states that are associated with maltreatment.

We utilized a longitudinal twin study (N = 2,510) to identify the child characteristics present prior to initiation of substance use that best predicted later substance use disorders. Two independent traits accounted for the majority of premorbid risk: socialization (conformity to rules and conventional values) and boldness (sociability and social assurance, stress resilience, and thrill seeking). Low socialization was associated with disruptive behavior disorders, parental externalizing disorders, and environmental adversity and exhibited moderate genetic (0.45) and shared environmental influences (0.30). Boldness was highly heritable (0.71) and associated with less internalizing distress and environmental adversity. In combination, these traits exhibited robust associations with adolescent and young adult substance use disorders (R = .48 and .50, respectively) and incremental prediction over disruptive behavior disorders, parental externalizing disorders, and environmental adversity. The results were replicated in an independent sample. Socialization and boldness offer a novel conceptualization of underlying risk for substance use disorders that has the potential to improve prediction and theory with implications for basic research, prevention, and intervention.

Few studies have investigated the role of gene × environment interactions (G × E) in speech, language, and literacy disorders. Currently, there are two theoretical models, the diathesis–stress model and the bioecological model, that make opposite predictions about the expected direction of G × E, because environmental risk factors may either strengthen or weaken the effect of genes on phenotypes. The purpose of the current study was to test for G × E at two speech sound disorder and reading disability linkage peaks using a sib-pair linkage design and continuous measures of socioeconomic status, home language/literacy environment, and number of ear infections. The interactions were tested using composite speech, language, and preliteracy phenotypes and previously identified linkage peaks on 6p22 and 15q21. Results showed five G × E at both the 6p22 and 15q21 locations across several phenotypes and environmental measures. Four of the five interactions were consistent with the bioecological model of G × E. Each of these four interactions involved environmental measures of the home language/literacy environment. The only interaction that was consistent with the diathesis–stress model was one involving the number of ear infections as the environmental risk variable. The direction of these interactions and possible interpretations are explored in the discussion.

Sleep disturbance is a symptom of and a well-known risk factor for depression. Further, atypical functioning of the HPA axis has been linked to the pathogenesis of depression. The purpose of this study was to examine the role of adolescent HPA axis functioning in the link between adolescent sleep problems and later depressive symptoms. Methods: A sample of 157 17–18 year old adolescents (61.8% female) completed the Pittsburgh Sleep Quality Inventory (PSQI) and provided salivary cortisol samples throughout the day for three consecutive days. Two years later, adolescents reported their depressive symptoms via the Center for Epidemiological Studies Depression Scale (CES-D). Results: Individuals (age 17–18) with greater sleep disturbance reported greater depressive symptoms two years later (age 19–20). This association occurred through the indirect effect of sleep disturbance on the cortisol awakening response (CAR) (indirect effect = 0.14, 95%CI [.02 -.39]). Conclusions: One pathway through which sleep problems may lead to depressive symptoms is by up-regulating components of the body’s physiological stress response system that can be measured through the cortisol awakening response. Behavioral interventions that target sleep disturbance in adolescents may mitigate this neurobiological pathway to depression during this high-risk developmental phase.

In humans, it has been demonstrated that the serotonin transporter linked polymorphic region (5-HTTLPR) genotype moderates risk in the face of adversity. One mechanism by which stress could interact with genotype is via epigenetic modifications. We wanted to examine whether stress interacted with genotype to predict binding of a histone 3 protein trimethylated at lysine 3 (H3K4me3) that marks active promoters. The brains (N = 61) of male rhesus macaques that had been reared in the presence or absence of stress were archived and the hippocampusi dissected. Chromatin immunoprecipitation was performed with an antibody against H3K4me3 followed by sequencing on a SolexaG2A. The effects of age, genotype (5-HTTLPR long/long vs. short), and stress exposure (peer-reared vs. mother-reared) on levels of H3K4me3 binding were determined. We found effects of age and stress exposure. There was a decline in H3K4me3 from preadolescence to postadolescence and lower levels in peer-reared monkeys and no effects of genotype. When we controlled for age, however, we found that there were effects of 5-HTTLPR genotype and rearing condition on H3K4me3 binding. In a larger sample, we observed that cerebrospinal fluid 5-hydroxyindoleacetic acid levels were subject to interactive effects among age, rearing history, and genotype. Genes containing both genetic selection and epigenetic regulation may be particularly important in stress adaptation and development. We find evidence for selection at the solute carrier family C6 member 4 gene and observe epigenetic reorganization according to genotype, stress, and age. These data suggest that developmental stage may moderate effects of stress and serotonin transporter genotype in the emergence of alternative adaptation strategies and in the vulnerability to developmental or psychiatric disorders.

We examined the nature and directionality of associations between interparental discord and parenting practices in a sample of 227 mothers and fathers of kindergarten children over two measurement waves spaced 1 year apart. Cross-lagged models indicated that associations between interparental discord and maternal and paternal parenting practices (i.e., acceptance, discipline) were generally negligible with one exception: interparental discord at Time 1 predicted decreases in maternal acceptance from Time 1 to Time 2. However, consistent with the family systems conceptualization of the family as an open system, prospective associations among interparental and parent–child subsystems varied significantly as a function of parental depressive symptoms, interparental relationship insecurity, and child-rearing disagreements. The moderating role of adult characteristics commonly varied across the type of adult vulnerability (e.g., depressive symptoms, interparental relationship insecurity, child-rearing disagreements), dimension of parenting practices (e.g., maternal and paternal acceptance and inconsistent discipline), and the directionality of the paths between interparental and parent–child subsystems.This research was supported by the National Institute of Mental Health (Project R01 MH 57318) awarded to Patrick T. Davies and E. Mark Cummings. Melissa L. Sturge–Apple was supported by a postdoctoral National Research Service Award from the National Institute of Mental Health (F32 MH 66596). The authors are grateful to the children, parents, teachers, and school administrators who participated in this project. Gratitude is also expressed to the staff who assisted with the project, including Courtney Forbes, Marcie Goeke–Morey, Amy Keller, Michelle Sutton, and the graduate and undergraduate students at the University of Rochester and the University of Notre Dame.

We investigated narratives, symbolic play, and emotions in children who varied in severity of disruptive behavior problems. Children's representations of hypothetical situations of conflict and distress were assessed at 4–5 and 7 years. Behavior problems also were assessed then and again at 9 years. Children's aggressive and caring themes differentiated nonproblem children, children whose problems remained or worsened with age, and those whose problems improved over time. Differences in boys and girls whose problems continued sometimes reflected exaggerations of prototypic gender differences seen across the groups. Boys with problems showed more hostile themes (physical aggression and anger), whereas girls with problems showed more caring (prosocial) themes relative to the other groups. Modulated (verbal) aggression, more common in girls than boys, showed developmentally appropriate increases with age. However, this was true only for children without problems and those whose problems improved. We consider how these findings contribute to an understanding the inner worlds of boys and girls who differ in their early developmental trajectories for behavior problems.

Disorganized attachment is an important early risk factor for socioemotional problems throughout childhood and into adulthood. Prevailing models of the etiology of disorganized attachment emphasize the role of highly dysfunctional parenting, to the exclusion of complex models examining the interplay of child and parental factors. Decades of research have established that extreme child birth weight may have long-term effects on developmental processes. These effects are typically negative, but this is not always the case. Recent studies have also identified the dopamine D4 receptor (DRD4) as a moderator of childrearing effects on the development of disorganized attachment. However, there are inconsistent findings concerning which variant of the polymorphism (seven-repeat long-form allele or non–seven-repeat short-form allele) is most likely to interact with caregiving in predicting disorganized versus organized attachment. In this study, we examined possible two- and three-way interactions and child DRD4 polymorphisms and birth weight and maternal caregiving at age 6 months in longitudinally predicting attachment disorganization at 36 months. Our sample is from the Maternal Adversity, Vulnerability and Neurodevelopment project, a sample of 650 mother–child dyads. Birth weight was cross-referenced with normative data to calculate birth weight percentile. Infant DRD4 was obtained with buccal swabs and categorized according to the presence of the putative allele seven repeat. Macroanalytic and microanalytic measures of maternal behavior were extracted from a videotaped session of 20 min of nonfeeding interaction followed by a 10-min divided attention maternal task at 6 months. Attachment was assessed at 36 months using the Strange Situation procedure, and categorized into disorganized attachment and others. The results indicated that a main effect for DRD4 and a two-way interaction of birth weight and 6-month maternal attention (frequency of maternal looking away behavior) and sensitivity predicted disorganized attachment in robust logistic regression models adjusted for social demographic covariates. Specifically, children in the midrange of birth weight were more likely to develop a disorganized attachment when exposed to less attentive maternal care. However, the association reversed with extreme birth weight (low and high). The DRD4 seven-repeat allele was associated with less disorganized attachment (protective), while non–seven-repeat children were more likely to be classified as disorganized attachment. The implications for understanding inconsistencies in the literature about which DRD4 genotype is the risk direction are also considered. Suggestions for intervention with families with infants at different levels of biological risk and caregiving risk are also discussed.

The prenatal environment shapes the offspring's phenotype; moreover, transgenerational stress and stress during pregnancy may play a role. Brain-derived neurotrophic factor (BDNF) and glucocorticoids influence neurodevelopment during pregnancy, and there is evidence that BDNF in amniotic fluid is mainly of fetal origin, while the source of glucocorticoids is maternal. We tested the hypothesis that maternal early life stress, psychiatric diagnoses, anxiety, perceived stress, and socioeconomic status influence BDNF and glucocorticoid concentrations in amniotic fluid in the second trimester. We studied 79 pregnant women who underwent amniocentesis in the early second trimester and analyzed BDNF, cortisol, and cortisone concentrations in amniotic fluid. The endocrine data were related to maternal early life adversities (Childhood Trauma Questionaire), perceived stress (Perceived Stress Scale), anxiety, socioeconomic status (family income), and the presence of psychiatric diseases. We found BDNF in amniotic fluid to be positively related to maternal early adversity (Childhood Trauma Questionaire). Low family income (socioeconomic status) was related to high amniotic fluid glucocorticoid concentrations. Neither glucocorticoid concentrations nor hydroxy steroid dehydrogenase (HSD2) activity could be related to BDNF concentrations in amniotic fluid. Early maternal adverse events may be reflected in the fetal BDNF regulation, and it should be tested whether this relates to differences in neurodevelopment.

The dopamine active transporter 1 (DAT1) gene is implicated in psychopathology risk. Although the processes by which this gene exerts its effects on risk are poorly understood, a small body of research suggests that the DAT1 gene influences early emerging negative emotionality, a marker of children's psychopathology risk. As child negative emotionality evokes negative parenting practices, the DAT1 gene may also play a role in gene–environment correlations. To test this model, children (N = 365) were genotyped for the DAT1 gene and participated in standardized parent–child interaction tasks with their primary caregiver. The DAT1 gene 9-repeat variant was associated with child negative affect expressed toward the parent during parent–child interactions, and parents of children with a 9-repeat allele exhibited more hostility and lower guidance/engagement than parents of children without a 9-repeat allele. These gene–environment associations were partially mediated by child negative affect toward the parent. The findings implicate a specific polymorphism in eliciting negative parenting, suggesting that evocative associations play a role in elevating children's risk for emotional trajectories toward psychopathology risk.

The observations of family members as well as the results of past research suggest that a variety of developmental pathways can precede the onset of schizophrenia in early adulthood. In this article, we describe recent findings from our research on the childhood precursors of schizophrenia. Taken together, the results indicate that childhood behavioral, emotional, and motoric dysfunction occur at a higher rate in preschizophrenia subjects when compared to control subjects. Further, there are developmental changes as well as significant variability among schizophrenia patients in the nature and severity of childhood impairment. Drawing on the prevailing diathesis-stress model, we explore the moderating role that stress exposure and reactivity may play in the expression of the organic diathesis for schizophrenia. Specifically, we consider the role of the biological stress response in the production of developmental changes and individual differences in the pathways to schizophrenia. Given extant models of dopamine involvement in the neuropathology of schizophrenia, stress-induced Cortisol release may alter the expression of subcortical abnormalities in dopamine neurotransmission. Thus, we present a neural mechanism for the hypothesized behavioral sensitivity to stress exposure in schizophrenia, and explore the capacity of the model to account for the changing behavioral manifestations of vulnerability.