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.

Etiological models propose that a biological vulnerability to emotional reactivity plays an important role in the development of borderline personality disorder (BPD). However, the physiological and phenomenological components of emotional reactivity that predict the course of BPD symptoms in adolescence are poorly understood. This prospective study examines pupillary and affective responses to maternal feedback as predictors of BPD symptom development in adolescent girls over 18 months. Fifty-seven 16-year-old girls completed a laboratory task in which they heard recorded clips of their own mothers making critical or praising statements about them, as well as neutral statements that did not pertain to them. Changes in girls’ pupil dilation and subjective affect were assessed throughout the task. The results demonstrated that greater pupillary response to maternal criticism predicted increases in BPD symptoms over time. In addition, greater pupillary and positive affective responses to maternal praise were associated with higher BPD symptoms at age 16 and faster decreases in BPD symptoms over time, but only among girls who heard clips that were rated by independent observers as less praising. The results suggest that emotional reactivity can serve as either a risk or a protective factor depending on context, with differential effects of reactivity to criticism versus praise.

The FK506 binding protein 5 gene (FKBP5) has been associated with susceptibility to pathogenic effects of childhood trauma including dissociative symptoms. This study examines the impact of maltreatment on dissociative tendencies in adolescence as moderated by the FKBP5 gene. Dissociative symptoms and variation within FKBP5 were assessed in a high-risk, low socioeconomic status community sample of 279 maltreated and 171 nonmaltreated adolescents. Following the assignment of haplotypes across four single nucleotide polymorphisms (rs3800373, rs9296158, rs1360780, and rs9470080), individuals with one or more copies of the CATT haplotype (N = 230) were grouped together and compared to individuals with zero copies of this haplotype (N = 185). Analyses of covariance were conducted to test hypotheses regarding the effects of developmental timing and the chronicity of maltreatment and the CATT haplotype. We found a significant interactive effect of timing/chronicity of maltreatment and the CATT haplotype on dissociative symptoms. Among adolescents who had no copies of the CATT haplotype, dissociative symptoms were higher for chronically maltreated adolescents who had an infancy onset compared to those who were not maltreated or whose maltreatment experience was either relatively less chronic or not started in infancy. The groups did not differ significantly among subjects who carry one or more copies of the CATT haplotype.

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.

Although a robust literature has linked stable, high levels of fear across childhood to increased risk for anxiety problems, less is known about alternative pathways to anxiety. We tested two putatively normative developmental pathways of early fearfulness for their distinct associations with behavioral (anxiety-related behaviors and symptoms) and biological (diurnal cortisol) markers of anxiety risk in middle childhood in a community-based sample (n = 107). Steeper increases in fear from 6 to 36 months predicted more parent-reported anxiety symptoms at age 8 years. In addition, children who exhibited steep increases in fear during infancy were overrepresented among children with diagnoses of separation anxiety disorder at age 8 years. Finally, we showed that steeper increases in fearfulness in infancy predicted flatter slopes of diurnal cortisol at age 8 years for girls. Thus, differences in stranger fear across infancy may indicate varying degrees of risk for anxious behaviors in later childhood.

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.