The present study tested the role of FKBP5 binding protein 5 (FKBP5) genetic variation in an internalizing pathway from child maltreatment to emerging adult problem drinking among a sample of African American youth (N = 280) followed prospectively from ages 11 to 20. Specifically, whether childhood internalizing symptoms and emerging adult tension reduction alcohol expectancies sequentially mediate the effect of child maltreatment on emerging adult problem drinking and whether FKBP5 moderates these associations were investigated. The results indicate that individuals with at least one copy of the FKBP5 CATT haplotype (minor alleles) are more vulnerable to traversing the hypothesized internalizing pathway of risk than individuals without this genotypic profile. Taken together our findings highlight the importance of FKBP5 genetic variation in the context of early adversity; support the role of two prospective sequential mediators of an internalizing pathway to problematic drinking, namely, childhood internalizing symptoms and emerging adult tension reduction alcohol expectancies; and identify a subgroup of maltreated children most susceptible to progressing along this less common pathway of risk.

Adolescent psychotic experiences increase risk for schizophrenia and other severe psychopathology in adulthood. Converging evidence implicates urban and adverse neighborhood conditions in the etiology of adolescent psychotic experiences, but the role of young people's personal perceptions of disorder (i.e., physical and social signs of threat) in their neighborhood is unknown. This was examined using data from the Environmental Risk Longitudinal Twin Study, a nationally representative birth cohort of 2,232 British twins. Participants were interviewed at age 18 about psychotic phenomena and perceptions of disorder in the neighborhood. Multilevel, longitudinal, and genetically sensitive analyses investigated the association between perceptions of neighborhood disorder and adolescent psychotic experiences. Adolescents who perceived higher levels of neighborhood disorder were significantly more likely to have psychotic experiences, even after accounting for objectively/independently measured levels of crime and disorder, neighborhood- and family-level socioeconomic status, family psychiatric history, adolescent substance and mood problems, and childhood psychotic symptoms: odds ratio = 1.62, 95% confidence interval [1.27, 2.05], p < .001. The phenotypic overlap between adolescent psychotic experiences and perceptions of neighborhood disorder was explained by overlapping common environmental influences, rC = .88, 95% confidence interval [0.26, 1.00]. Findings suggest that early psychological interventions to prevent adolescent psychotic experiences should explore the role of young people's (potentially modifiable) perceptions of threatening neighborhood conditions.

A wealth of evidence documents associations between various aspects of the rearing environment and later development. Two evolutionary-inspired models advance explanations for why and how such early experiences shape later functioning: (a) the external-prediction model, which highlights the role of the early environment (e.g., parenting) in regulating children's development, and (b) the internal-prediction model, which emphasizes internal state (i.e., health) as the critical regulator. Thus, by using data from the NICHD Study of Early Child Care and Youth Development, the current project draws from both models by investigating whether the effect of the early environment on later adolescent functioning is subject to an indirect effect by internal-health variables. Results showed a significant indirect effect of internal health on the relation between the early environment and adolescent behavior. Specifically, early environmental adversity during the first 5 years of life predicted lower quality health during childhood, which then led to problematic adolescent functioning and earlier age of menarche for girls. In addition, for girls, early adversity predicted lower quality health that forecasted earlier age of menarche leading to increased adolescent risk taking. The discussion highlights the importance of integrating both internal and external models to further understand the developmental processes that effect adolescent behavior.

Early life stress (ELS) is a significant risk factor for the emergence of internalizing problems in adolescence. Beginning in adolescence, females are twice as likely as males to experience internalizing disorders. The present study was designed to examine sex differences in the association between ELS and internalizing problems in early pubertal adolescents, and whether and how corticolimbic function and connectivity may underlie these associations. Fifty-nine early pubertal males and 78 early pubertal females, ages 9–13 years (all Tanner Stage 3 or below) underwent functional magnetic resonance imaging as they performed an emotion label task that robustly interrogates corticolimbic function. Participants were also interviewed about their experience of ELS. Females exhibited a positive association between ELS and internalizing problems, whereas males exhibited no such association. Whole-brain and amygdala region of interest analyses indicated that whereas females exhibited a positive association between ELS and the ventrolateral prefrontal cortex during implicit emotion regulation, males showed no such association. Activation in these regions was positively associated with internalizing problems in females but not males; however, activation in these regions did not mediate the association between ELS and internalizing problems. Finally, both boys and girls exhibited an association between ELS and increased negative connectivity between the right ventrolateral prefrontal cortex and bilateral amygdala. Using a carefully characterized sample of early pubertal adolescents, the current study highlights important sex differences in the development of corticolimbic circuitry during a critical period of brain development. These sex differences may play a significant role in subsequent risk for internalizing problems.

Early caregiving adversity is associated with increased risk for social difficulties. The ventral striatum and associated corticostriatal circuitry, which have demonstrated vulnerability to early exposures to adversity, are implicated in many aspects of social behavior, including social play, aggression, and valuation of social stimuli across development. Here, we used resting-state functional magnetic resonance imaging to assess the degree to which early caregiving adversity was associated with altered coritocostriatal resting connectivity in previously institutionalized youth (n = 41) relative to youth who were raised with their biological families from birth (n = 47), and the degree to which this connectivity was associated with parent-reported social problems. Using a seed-based approach, we observed increased positive coupling between the ventral striatum and anterior regions of medial prefrontal cortex (mPFC) in previously institutionalized youth. Stronger ventral striatum–mPFC coupling was associated with parent reports of social problems. A moderated-mediation analysis showed that ventral striatal–mPFC connectivity mediated group differences in social problems, and more so with increasing age. These findings show that early institutional care is associated with differences in resting-state connectivity between the ventral striatum and the mPFC, and this connectivity seems to play an increasingly important role in social behaviors as youth enter adolescence.

Childhood adversity (CA) is known to predict sensitization to proximal stressors. Researchers have suggested that disruptions in hypothalamus–pituitary–adrenal axis functioning may be a biological mechanism. If so, CA may predict altered associations between proximal life stress and markers of cortisol secretion. We examined whether CA moderates associations between recent episodic stress and (a) the cortisol awakening response (CAR), and (b) depressive symptoms, in 241 adolescents aged 14–17 years (cortisol n = 196). Salivary cortisol was sampled at 0, 30, and 60 min postawakening for 2 days. The CAR was calculated as the area under the curve with respect to increase and waking cortisol. CA and episodic stress were assessed using contextual-threat-method-coded objective interviews. CA significantly interacted with episodic stress to predict both the CAR and depression. Among those with low CA, episodic stress predicted increased CAR but did not predict depression. For adolescents with high CA, episodic stress predicted lower CAR and higher depression. These interactions were found only for independent (uncontrollable, fateful) events, and not for dependent (self-generated) stress. Increased allostatic load resulting from CA exposure may interfere with adolescents' ability to optimally regulate their CAR in relation to recent stress, contributing to increased depression risk.

Individuals who have experienced high levels of childhood stress are at increased risk for a wide range of behavioral problems that persist into adulthood, yet the neurobiological and molecular mechanisms underlying these associations remain poorly understood. Many of the difficulties observed in stress-exposed children involve problems with learning and inhibitory control. This experiment was designed to test individuals' ability to learn to inhibit responding during a laboratory task. To do so, we measured stress exposure among a community sample of school-aged children, and then followed these children for a decade. Those from the highest and lowest quintiles of childhood stress exposure were invited to return to our laboratory as young adults. At that time, we reassessed their life stress exposure, acquired functional magnetic resonance imaging data during an inhibitory control task, and assayed these individuals' levels of methylation in the FK506 binding protein 5 (FKBP5) gene. We found that individuals who experienced high levels of stress in childhood showed less differentiation in the dorsolateral prefrontal cortex between error and correct trials during inhibition. This effect was associated only with childhood stress exposure and not by current levels of stress in adulthood. In addition, FKBP5 methylation mediated the association between early life stress and inhibition-related prefrontal activity. These findings are discussed in terms of using multiple levels of analyses to understand the ways in which adversity in early development may affect adult behavioral adaptation.

While striving to succeed in the face of adversity may provide individuals with outward benefits, it may come at a cost to individuals’ physical health. The current study examines whether striving predicts greater physiological or psychosocial costs among those who experienced child maltreatment, a stressor that disrupts the caregiving environment and threatens relationship security. Using data from the National Longitudinal Study of Adolescent to Adult Health, we tested whether greater striving after childhood maltreatment would come at a cost, increasing underlying cardiovascular disease (CVD) risk and depressive symptoms despite showing outward success via income and college degree attainment. The study included 13,341 Black, Hispanic, and White adolescents who self-reported striving and their experiences of childhood neglect, physical abuse, and sexual abuse. As young adults, participants reported depressive symptoms, income, and college degree attainment and completed a health assessment from which a 30-year Framingham-based CVD risk score was calculated. Higher striving was associated with lower CVD risk and depressive symptoms, and higher income and college degree attainment, regardless of maltreatment history. These findings highlight the potential for striving as a target for interventions and support the need to examine multiple biological and behavioral outcomes to understand the multifaceted nature of resilience.

While environmental adversity has been shown to increase risk for psychopathology, individuals differ in their sensitivity to these effects. Both genes and childhood experiences are thought to influence sensitivity to the environment, and these factors may operate synergistically such that the effects of childhood experiences on later sensitivity are greater in individuals who are more genetically sensitive. In line with this hypothesis, several recent studies have reported a significant three-way interaction (Gene × Environment × Environment) between two candidate genes and childhood and adult environment on adult psychopathology. We aimed to replicate and extend these findings in a large, prospective multiwave longitudinal study using a polygenic score of environmental sensitivity and objectively measured childhood and adult material environmental quality. We found evidence for both Environment × Environment and Gene × Environment × Environment effects on psychological distress. Children with a poor-quality material environment were more sensitive to the negative effects of a poor environment as adults, reporting significantly higher psychological distress scores. These effects were further moderated by a polygenic score of environmental sensitivity. Genetically sensitive children were more vulnerable to adversity as adults, if they had experienced a poor childhood environment but were significantly less vulnerable if their childhood environment was positive. These findings are in line with the differential susceptibility hypothesis and suggest that a life course approach is necessary to elucidate the role of Gene × Environment in the development of mental illnesses.

Previous research suggests that the experience of abuse and neglect in childhood has negative implications for physical health in adulthood. Using data from the Minnesota Longitudinal Study of Risk and Adaptation (N = 115), the present research examined the predictive significance of childhood physical abuse, sexual abuse, and physical/cognitive neglect for multilevel assessments of physical health at midlife (age 37–39 years), including biomarkers of cardiometabolic risk, self-reports of quality of health, and a number of health problems. Analyses revealed that childhood physical/cognitive neglect, but not physical or sexual abuse, predicted all three health outcomes in middle adulthood, even when controlling for demographic risk factors and adult health maintenance behaviors. We discuss possible explanations for the unique significance of neglect in this study and suggest future research that could clarify previous findings regarding the differential impact of different types of abuse and neglect on adult health.

The current investigation utilized a developmental psychopathology approach to test the hypothesis that multigenic (i.e., dopaminergic and serotonergic genes) and multienvironmental factors interactively contribute to developmental pathways of antisocial behavior (ASB). A sample of 8,834 Caucasian individuals from the National Longitudinal Study of Adolescent to Adult Health (Add Health) were used to (a) examine the developmental pathways of ASB from age 13 to 32 using growth mixture modeling, (b) compute weighted multigenic risk scores (Add Health MRS) for ASB from six well-characterized polymorphisms in dopamine and serotonin genes, and (c) test the interaction between the Add Health MRS and a measures of support (incorporating indicators of both positive and negative support from parents and schools). Four pathways of adolescent to adult ASB emerged from the growth mixture models: low, adolescence-peaked, high decline, and persistent. Add Health MRS predicted the persistent ASB pathway, but not other ASB pathways. Males with high Add Health MRS, but not low MRS, had significantly greater odds of being in the adolescence-peaked pathway relative to the low pathway at low levels of school connectedness. Nonfamilial environmental influences during adolescence may have a cumulative impact on the development of ASB, particularly among males with greater underlying genetic risks.

Parent–child relationships have long-term effects on health, particularly later inflammation and depression. We hypothesized that these effects would be mediated by later romantic partner relationships and elevated stressors in young adulthood, helping promote chronic, low grade, inflammation as well as depressive symptoms, and driving their covariation. It has been proposed recently that youth experiencing harsher parenting may also develop a stronger association between inflammation and depressive symptoms in adulthood and altered effects of stressors on outcomes. In the current investigation, we test these ideas using an 18-year longitudinal study of N = 413 African American youth that provides assessment of the parent–child relationship (at age 10), pro-inflammatory cytokine profile and depressive symptoms (at age 28), and potential mediators in early young adulthood (assessed at ages 21 and 24). As predicted, the effect of harsher parent–child relationships (age 10) on pro-inflammatory state and increased depressive symptoms at age 28 were fully mediated through young adult stress and romantic partner relationships. In addition, beyond these mediated effects, parent–child relationships at age 10 moderated the concurrent association between inflammation and depressive symptoms, as well as the prospective association between romantic partner relationships and inflammation, and resulted in substantially different patterns of indirect effects from young adult mediators to outcomes. The results support theorizing that the association of depression and inflammation in young adulthood is conditional on earlier parenting, and suggest incorporating this perspective into models predicting long-term health outcomes.