The experience of child maltreatment is a significant risk factor for the development of later internalizing disorders such as depression and anxiety. This risk is particularly heightened after exposure to additional, more contemporaneous stress. While behavioral evidence exists for such “stress sensitization,” little is known about the mechanisms mediating such relationships, particularly within the brain. Here we report that the experience of child maltreatment independent of recent life stress, gender, and age is associated with reduced structural integrity of the uncinate fasciculus, a major white matter pathway between the amygdala and ventromedial prefrontal cortex, in young adults. We further demonstrate that individuals with lower uncinate fasciculus integrity at baseline who subsequently experience stressful life events report higher levels of internalizing symptomatology at follow-up. Our findings suggest a novel neurobiological mechanism linking child maltreatment with later internalizing symptoms, specifically altered structural connectivity within the brain's threat-detection and emotion-regulation circuitry.

We examined the role of infant temperament and maternal dispositional empathy in the neural processing of happy and fearful emotional body expressions in 8-month-old infants by measuring event-related brain potentials. Our results revealed that infants’ tendency to approach novel objects and people was positively correlated with the neural sensitivity (attention allocation) to fearful expressions, while infant fearfulness was negatively correlated to the neural sensitivity to fearful expressions. Maternal empathic concern was associated with infants’ neural discrimination between happy and fearful expression, with infants of more empathetically concerned mothers showing greater neural sensitivity (attention allocation) to fearful compared to happy expressions. It is critical that our results also revealed that individual differences in the sensitivity to emotional information are explained by an interaction between infant temperament and maternal empathic concern. Specifically, maternal empathy appears to impact infants’ neural responses to emotional body expressions, depending on infant fearfulness. These findings support the notion that the way in which infants respond to emotional signals in the environment is fundamentally linked to their temperament and maternal empathic traits. This adds an early developmental neuroscience dimension to existing accounts of social–emotional functioning, suggesting a complex and integrative picture of why and how infants’ emotional sensitivity varies.

Based on an emerging neuroscience model of addiction, this study examines how an imbalance between two neurobehavioral systems (reward motivation and executive control) can distinguish between early adolescent progressive drug use and mere experimentation with drugs. Data from four annual assessments of a community cohort (N = 382) of 11- to 13-year-olds were analyzed to model heterogeneity in patterns of early drug use. Baseline assessments of working memory (an indicator of the functional integrity of the executive control system) and three dimensions of impulsivity (characterizing the balance between reward seeking and executive control systems) were used to predict heterogeneous latent classes of drug use trajectories from early to midadolescence. Findings revealed that an imbalance resulting from weak executive control and heightened reward seeking was predictive of early progression in drug use, while heightened reward seeking balanced by a strong control system was predictive of occasional experimentation only. Implications of these results are discussed in terms of preventive interventions that can target underlying weaknesses in executive control during younger years, and potentially enable at-risk adolescents to exercise greater self-restraint in the context of rewarding drug-related cues.

Epigenetic modifications to the genome are a key mechanism involved in the biological encoding of experience. Animal studies and a growing body of literature in humans have shown that early adversity is linked to methylation of the gene for the glucocorticoid receptor (GR), which is a key regulator of the hypothalamic–pituitary–adrenal axis as well as a broad range of physiological systems including metabolic and immune function. One hundred eighty-four families participated, including n = 74 with child welfare documentation of moderate-severe maltreatment in the past 6 months. Children ranged in age from 3 to 5 years, and were racially and ethnically diverse. Structured record review and interviews in the home were used to assess a history of maltreatment, other traumas, and contextual life stressors, and a composite variable assessed the number exposures to these adversities. Methylation of regions 1D, 1F, and 1H of the GR gene was measured via sodium bisulfite pyrosequencing. The composite measure of adversity was positively correlated with methylation at exons 1D and 1F in the promoter of the GR gene. Individual stress measures were significantly associated with a several CpG sites in these regions. GR gene methylation may be a mechanism of the biobehavioral effects of adverse exposures in young children.

Previous research has found associations but not established mechanisms of developmental linkage between language ability and inattentive–hyperactive (I-H) behavior problems. The present study examined whether self-regulation mediates the effect of language ability on later I-H behavior problems among young children (N = 120) assessed at 30, 36, and 42 months of age. Cross-lagged panel models tested the direction of effect between language ability and self-regulation and longitudinal effects of language ability on later I-H problems mediated by self-regulation. Language ability was measured by children's scores on the receptive and expressive language subtests of the Differential Ability Scales. Self-regulation was measured by three behavioral tasks requiring inhibitory control. I-H problems were reported by parents and secondary caregivers. Language ability predicted later self-regulation as measured by all three tasks. There was no association, however, between self-regulation and later language ability, suggesting that the direction of effect was stronger from language ability to later self-regulation. Moreover, the effect of language ability on later I-H behavior problems was mediated by children's self-regulation in one of the tasks (for secondary caregivers' but not parents' ratings). Findings suggest that language deficits may explain later I-H behavior problems via their prediction of poorer self-regulatory skills.

Alcohol use and depressive feelings are often related among early adolescents. However, the nature and underlying mechanisms of this association are not yet clear. The aim of this study was to investigate the co-development of alcohol use and depressive feelings over time and to examine the effects of the mu-opioid receptor (OPRM1) A118G genotype on such co-development. Data from a five-wave longitudinal, genetically informed survey study, with intervals of 4 months among a group of 739 normative early adolescents (12–13 years of age at baseline), were analyzed using a dual latent growth curve approach. OPRM1 status was evaluated from saliva-derived DNA samples. The results indicated a positive association between alcohol use and depressive feelings both at the initial levels and over time, indicating co-development in early adolescence. Compared to OPRM1 118G carriers, homozygous 118A carriers showed a greater increase in frequency of alcohol use and higher levels of depressive feelings over time. Evidence for co-development was only found within the group of homozygous 118A carriers, whereas in OPRM1 118G carriers the development of alcohol use and depressive feelings over time were not significantly associated. These results highlight the potential of OPRM1 as a common etiological factor for the development of alcohol use and depressive feelings in early adolescence.

The emerging field of neurogenetics seeks to model the complex pathways from gene to brain to behavior. This field has focused on imaging genetics techniques that examine how variability in common genetic polymorphisms predict differences in brain structure and function. These studies are informed by other complimentary techniques (e.g., animal models and multimodal imaging) and have recently begun to incorporate the environment through examination of Imaging Gene × Environment interactions. Though neurogenetics has the potential to inform our understanding of the development of psychopathology, there has been little integration between principles of neurogenetics and developmental psychopathology. The paper describes a neurogenetics and Imaging Gene × Environment approach and how these approaches have been usefully applied to the study of psychopathology. Six tenets of developmental psychopathology (the structure of phenotypes, the importance of exploring mechanisms, the conditional nature of risk, the complexity of multilevel pathways, the role of development, and the importance of who is studied) are identified, and how these principles can further neurogenetics applications to understanding the development of psychopathology is discussed. A major issue of this piece is how neurogenetics and current imaging and molecular genetics approaches can be incorporated into developmental psychopathology perspectives with a goal of providing models for better understanding pathways from among genes, environments, the brain, and behavior.

This study examined the longitudinal implications of adolescents' exposure to interparental conflict for their developmental success. In the proposed developmental cascade model, adolescents' perceptions of parental conflict as threatening is a risk factor for diminished self-efficacy, which would account for diminished adjustment. This study presents longitudinal data for 768 sixth-grade students and their families over four time points, ending in eighth grade. Analyses were conducted in three steps. First, replication of longitudinal support for threat as a mediator of the link between interparental conflict and emotional distress was found; however, findings did not support threat as a mediator of behavior problems or subjective well-being. Second, threat was found to mediate the longitudinal association between interparental conflict and self-efficacy. Third, a developmental cascade model supported a risk process in which interparental conflict was related to adolescents' threat appraisals, which undermined self-efficacy beliefs, and was then linked with emotional distress, behavior problems, and subjective well-being.

A model examining the effects of an increasing number of maltreatment subtypes experienced on antisocial behavior, as mediated by impulsivity and moderated by a polygenic index of dopaminergic genotypes, was investigated. An African American sample of children (N = 1,012, M age = 10.07) with and without maltreatment histories participated. Indicators of aggression, delinquency, and disruptive peer behavior were obtained from peer- and counselor-rated measures to form a latent variable of antisocial behavior; impulsivity was assessed by counselor report. Five genotypes in four dopaminergic genes (dopamine receptors D4, D2, known as DRD4, DRD2; dopamine active transporter 1, known as DAT1; and catechol-O-methyltransferase, known as COMT) conferring heightened environmental sensitivity were combined into one polygenic index. Using structural equation modeling, a first-stage, moderated-mediation model was evaluated. Age and sex were entered as covariates, both as main effects and in interaction with maltreatment and the gene index. The model had excellent fit: χ2 (32, N = 1,012) = 86.51, p < .001; comparative fit index = 0.982, Tucker–Lewis index = 0.977, root mean square error of approximation = 0.041, and standardized root mean square residual = 0.022. The effect of maltreatment subtypes on antisocial behavior was partially mediated by impulsivity (β = 0.173, p < .001), and these relations were moderated by the number of differentiating dopaminergic genotypes. Specifically, a significant Gene × Environment interaction (β = 0.016, p = .013) indicated that the relation between maltreatment and impulsivity was stronger as children evinced more differentiating genotypes, thereby strengthening the mediational effect of impulsivity on antisocial behavior. These findings elucidate the manner by which maltreated children develop early signs of antisocial behavior, and the genetic mechanisms involved in greater vulnerability for maladaptation in impulse control within the context of child maltreatment.

Socioeconomic status (SES) is relatively stable across generations, but social policies may create opportunities for upward social mobility among disadvantaged populations during periods of economic growth. With respect to expanded educational opportunities that occurred in Québec (Canada) during the 1960s, we hypothesized that children's social and academic competence would promote upward mobility, whereas aggression and social withdrawal would have the opposite effect. Out of 4,109 children attending low-SES schools in 1976–1978, a representative subsample of 503 participants were followed until midadulthood. Path analyses revealed that parents’ SES predicted offspring's SES through associations with offspring's likeability, academic competence, and educational attainment. Interaction effects revealed individual risk factors that moderated children's ability to take advantage of intrafamilial or extrafamilial opportunities that could enhance their educational attainment. Highly aggressive participants and those presenting low academic achievement were unable to gain advantage from having highly educated parents. They reached lower educational attainment than their less aggressive or higher achieving peers who came from a similarly advantaged family background. Growing up with parents occupying low-prestige jobs put withdrawn boys and outgoing girls at risk for low educational attainment. In conclusion, social policies can raise SES across generations, with great benefits for the most disadvantaged segments of the population. However, children presenting with emerging psychopathology or academic weaknesses do not benefit from these policies as much as others, and should receive additional, targeted services.

This paper examines the relationship between childhood exposure to cumulative risk and three indicators of psychosocial adjustment in adulthood (educational attainment, mental health, and criminal behavior) and tests three different models (linear, quadratic, and interaction). Data were collected over several time points from individuals who were part of a prospective cohort design study that matched children with documented cases of abuse and/or neglect with children without such histories and followed them into adulthood. Hierarchical multiple regressions compared linear and quadratic models and then examined potential moderating effects of child abuse/neglect and gender. Exposure to a greater number of childhood risk factors was significantly related to fewer years of education, more anxiety and depression symptomatology, and more criminal arrests in adulthood. The relationship between cumulative risk and years of education demonstrated a curvilinear pattern, whereas the relationship between cumulative risk and both mental health and criminal arrests was linear. Child abuse/neglect did not moderate these relationships, although there were direct effects for both child abuse/neglect and gender on criminal arrests, with more arrests for abused/neglected individuals than controls and more for males than females. Gender interacted with cumulative risk to impact educational attainment and criminal behavior, suggesting that interventions may be more effective if tailored differently for males and females. Interventions may need to be multifaceted and designed to address these different domains of functioning.

This study examined the extent to which secure base script knowledge—reflected in the ability to generate narratives in which attachment-relevant events are encountered, a clear need for assistance is communicated, competent help is provided and accepted, and the problem is resolved—is associated with mothers’ electrophysiological, subjective, and observed emotional responses to an infant distress vocalization. While listening to an infant crying, mothers (N = 108, M age = 34 years) lower on secure base script knowledge exhibited smaller shifts in relative left (vs. right) frontal EEG activation from rest, reported smaller reductions in feelings of positive emotion from rest, and expressed greater levels of tension. Findings indicate that lower levels of secure base script knowledge are associated with an organization of emotional responding indicative of a less flexible and more emotionally restricted response to infant distress. Discussion focuses on the contribution of mothers’ attachment representations to their ability to effectively manage emotional responding to infant distress in a manner expected to support sensitive caregiving.

Substance use trajectories were examined from early adolescence to young adulthood among a diverse sample of 998 youths. Analysis of longitudinal data from ages 12 to 24 identified distinct trajectories for alcohol, marijuana, and tobacco use. Modeling revealed 8 alcohol, 7 marijuana, and 6 tobacco use trajectories. Analyses assessed risk for substance use problems in early adulthood within each trajectory, as well as overlap among alcohol, marijuana, and tobacco use trajectories. Findings confirmed that adolescents with early- and rapid-onset trajectories are particularly vulnerable to the development of problematic substance use in early adulthood. However, analyses also identified an escalating high school onset trajectory for alcohol and for marijuana use that was equally prognostic of problem use in adulthood. Moreover, tobacco use in early adolescence was associated with developing high-risk marijuana and alcohol use patterns. Random assignment to the Family Check-Up intervention was found to reduce risk for membership in the high-risk marijuana use trajectories, suggesting that family-based approaches delivered during adolescence can prevent escalations to problematic substance use. These findings suggest the importance of developmental heterogeneity and equifinality in considering prevention for alcohol and drug use.

A growing body of evidence suggests that alterations of the stress response system may be a mechanism by which childhood maltreatment alters risk for psychopathology. FK506 binding protein 51 (FKBP5) binds to the glucocorticoid receptor and alters its ability to respond to stress signaling. The aim of the present study was to examine methylation of the FKBP5 gene (FKBP5), and the role of an FKBP5 genetic variant, in relation to childhood maltreatment in a sample of impoverished preschool-aged children. One hundred seventy-four families participated in this study, including 69 with child welfare documentation of moderate to severe maltreatment in the past 6 months. The children, who ranged in age from 3 to 5 years, were racially and ethnically diverse. Structured record review and interviews in the home were used to assess a history of maltreatment, other traumas, and contextual life stressors; and a composite variable assessed the number exposures to these adversities. Methylation of two sites in intron 7 of FKBP5 was measured via sodium bisulfite pyrosequencing. Maltreated children had significantly lower levels of methylation at both CpG sites (p < .05). Lifetime contextual stress exposure showed a trend for lower levels of methylation at one of the sites, and a trend for an interaction with the FKBP5 polymorphism. A composite adversity variable was associated with lower levels of methylation at one of the sites as well (p < .05). FKBP5 alters glucocorticoid receptor responsiveness, and FKBP5 gene methylation may be a mechanism of the biobehavioral effects of adverse exposures in young children.

In this paper, we review the history of the concept of neuroplasticity as it relates to the understanding of neuropsychiatric disorders, using schizophrenia as a case in point. We briefly review the myriad meanings of the term neuroplasticity, and its neuroscientific basis. We then review the evidence for aberrant neuroplasticity and metaplasticity associated with schizophrenia as well as the risk for developing this illness, and discuss the implications of such understanding for prevention and therapeutic interventions. We argue that the failure and/or altered timing of plasticity of critical brain circuits might underlie cognitive and deficit symptoms, and may also lead to aberrant plastic reorganization in other circuits, leading to affective dysregulation and eventually psychosis. This “dysplastic” model of schizophrenia can suggest testable etiology and treatment-relevant questions for the future.

Adolescent psychopathology is commonly connected to marijuana use. How changes in these adolescent antecedents and in adolescent marijuana use are connected to patterns of marijuana use in the 20s is little understood. Another issue not clearly understood is psychopathology in the 30s as predicted by marijuana use in the 20s. This study sought to examine these two issues and the associations with marijuana disorder diagnoses using a longitudinal data set of 205 men with essentially annual reports. Individual psychopathology and family characteristics from the men's adolescence were used to predict their patterns of marijuana use across their 20s, and aspects of the men's psychopathology in their mid-30s were predicted from these patterns. Three patterns of marijuana use in the 20s were identified using growth mixture modeling and were associated with diagnoses of marijuana disorders at age 26 years. Parental marijuana use predicted chronic use for the men in adulthood. Patterns of marijuana use in the 20s predicted antisocial behavior and deviant peer association at age 36 years (controlling for adolescent levels of the outcomes by residualization). These findings indicate that differential patterns of marijuana use in early adulthood are associated with psychopathology toward midlife.

This article highlights the defining principles, progress, and future directions in epigenetics research in relation to this Special Issue. Exciting studies in the fields of neuroscience, psychology, and psychiatry have provided new insights into the epigenetic factors (e.g., DNA methylation) that are responsive to environmental input and serve as biological pathways in behavioral development. Here we highlight the experimental evidence, mainly from animal models, that factors such as psychosocial stress and environmental adversity can become encoded within epigenetic factors with functional consequences for brain plasticity and behavior. We also highlight evidence that epigenetic marking of genes in one generation can have consequences for future generations (i.e., inherited), and work with humans linking epigenetics, cognitive dysfunction, and psychiatric disorder. Though epigenetics has offered more of a beginning than an answer to the centuries-old nature–nurture debate, continued research is certain to yield substantial information regarding biological determinants of central nervous system changes and behavior with relevance for the study of developmental psychopathology.

This study examined the hypothesis that a brief, strengths-based home visiting strategy can promote positive engagement between caregiver and child and thereby reduce various forms of early childhood neglect. A total of 731 low-income families receiving services through the Women, Infants, and Children nutritional supplement program were randomized to the Women, Infants, and Children as usual or the Family Check-Up intervention. Assessments and intervention services were delivered in the home environment at ages 2, 3, 4, and 5. During the assessments, staff videotaped caregiver–child interactions and rated various features of the home environment, including the physical appropriateness of the home setting for children. Trained observers later coded the videotapes, unaware of the family's intervention condition. Specific caregiver–child interaction patterns were coded and macroratings were made of the caregiver's affection, monitoring, and involvement with the child. An intention to treat design revealed that randomization to the Family Check-Up increased duration of positive engagement between caregivers and children by age 3, which in turn was prognostic of less neglect of the child at age 4, controlling for family adversity. It was also found that family adversity moderated the impact of the intervention, such that the families with the most adverse circumstances were highly responsive to the intervention. Families with the highest levels of adversity exhibited the strongest mediation between positive engagement and reduction of neglect. Findings are discussed with respect to developmental theory and their potential implications for a public health approach to the prevention of early childhood maltreatment.

Past research has documented pervasive genetic influences on emotional and behavioral disturbance across the life span and on liability to adult psychiatric disorder. Increasingly, interest is turning to mechanisms of gene–environment interplay in attempting to understand the earliest manifestations of genetic risk. We report findings from a prospective adoption study, which aimed to test the role of evocative gene–environment correlation in early development. Included in the study were 561 infants adopted at birth and studied between 9 and 27 months, along with their adoptive parents and birth mothers. Birth mother psychiatric diagnoses and symptoms scales were used as indicators of genetic influence, and multiple self-report measures were used to index adoptive mother parental negativity. We hypothesized that birth mother psychopathology would be associated with greater adoptive parent negativity and that such evocative effects would be amplified under conditions of high adoptive family adversity. The findings suggested that genetic factors associated with birth mother externalizing psychopathology may evoke negative reactions in adoptive mothers in the first year of life, but only when the adoptive family environment is characterized by marital problems. Maternal negativity mediated the effects of genetic risk on child adjustment at 27 months. The results underscore the importance of genetically influenced evocative processes in early development.