Epigenetics processes may play a vital role in the biological embedding of early environmental adversity and the development of psychopathology. Accumulating evidence suggests that maltreatment is linked to methylation of the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), which is a key regulator of the hypothalamus–pituitary–adrenal axis. However, prior work has been exclusively cross-sectional, greatly constraining our understanding of stress-related epigenetic processes over time. In the current study, we examined the effect of maltreatment and other adversity on change in NR3C1 methylation among at-risk preschoolers to begin to characterize within-child epigenetic changes during this sensitive developmental period. Participants were 260 preschoolers (3–5 years old, 53.8% female), including 51.5% with moderate to severe maltreatment in the past 6 months. Child protection records, semistructured interviews, and parent reports were used to assess child stress exposure. Methylation of exons 1D and 1F of NR3C1 via saliva DNA were measured at two time points approximately 6 months apart. Results indicate that maltreated children evidence higher baseline levels of NR3C1 methylation, significant decreases in methylation over time, and then at follow-up, lower levels of methylation, relative to nonmaltreated preschoolers. Findings from the current study highlight the complex nature of stress-related epigenetic processes during early development.

We hypothesized that presence of the short allele in the promoter region of the serotonin transporter would moderate the effect of early cumulative socioeconomic status (SES) risk on epigenetic change among African American youth. Contrasting hypotheses regarding the shape of the interaction effect were generated using vulnerability and susceptibility frameworks and applied to data from a sample of 388 African American youth. Early cumulative SES risk assessed at 11–13 years based on parent report interacted with presence of the short allele to predict differential methylation assessed at age 19. Across multiple tests, a differential susceptibility perspective rather than a diathesis–stress framework best fit the data for genes associated with depression, consistently demonstrating greater epigenetic response to early cumulative SES risk among short allele carriers. A pattern consistent with greater impact among short allele carriers also was observed using all cytosine nucleotide–phosphate–guanine nucleotide sites across the genome that were differentially affected by early cumulative SES risk. We conclude that the short allele is associated with increased responsiveness to early cumulative SES risk among African American youth, leading to epigenetic divergence for depression-related genes in response to exposure to heightened SES risk among short allele carriers in a “for better” or “for worse” pattern.

Polymorphisms in the oxytocin receptor gene are commonly associated with prosocial behaviors in the extant literature, yet their role in antisocial behaviors has rarely been explored, particularly during the transition from adolescence to early adulthood. We examined a prospective cohort (N = 404), collecting youth, mother, and clinician reports of conduct-disordered and antisocial behavior at ages 15 and 20. The oxytocin receptor gene rs53576 polymorphism was hypothesized to interact with social stress to predict antisocial outcomes. Structural equation modeling results revealed a significant main effect at age 15 (p = .025); those with the G allele exhibited higher levels of conduct problems. Structural equation modeling revealed a significant Gene × Environment interaction at age 20 (p = .029); those with the G allele who experienced high social stress exhibited higher levels of antisocial behavior. Heterozygous (AG) grouping models were compared, and parameter estimations supported G dominant groupings. These novel findings suggest that rs53576 polymorphisms may influence social salience and contribute to risk for antisocial outcomes, particularly under conditions of high social stress.

Attachment theory and research have traditionally been subspecialties in infant social development. Recent work has extended the relevance of attachment theory and assessments well into childhood and has established firm ties to work with adults. Many of the same variables associated with the development of disruptive behavior problems also influence the development of attachment. In addition, recent data point to consistent relations between attachment status and disruptive behavior problems. This paper reviews attachment theory, summarizes mechanisms through which attachment might be related to disruptive behavior problems, and discusses the relevance of attachment theory to prevention and therapy. We emphasize the diversity of possible relations between attachment and disruptive behavior problems and the fact that incorporating attachment theory into research on disruptive behavior problems does not mean interpreting every disruptive behavior as attachment related or every attachment-related disruption as serving the same function.

Transactional cascades among child internalizing and externalizing symptoms, and fathers’ and mothers’ posttraumatic stress disorder (PTSD) symptoms were examined in a sample of families with a male parent who had been deployed to recent military conflicts in the Middle East. The role of parents’ positive engagement and coercive interaction with their child, and family members’ emotion regulation were tested as processes linking cascades of parent and child symptoms. A subsample of 183 families with deployed fathers and nondeployed mothers and their 4- to 13-year-old children who participated in a randomized control trial intervention (After Deployment: Adaptive Parenting Tools) were assessed at baseline prior to intervention, and at 12 and 24 months after baseline, using parent reports of their own and their child's symptoms. Parents’ observed behavior during interaction with their children was coded using a multimethod approach at each assessment point. Reciprocal cascades among fathers’ and mothers’ PTSD symptoms, and child internalizing and externalizing symptoms, were observed. Fathers’ and mothers’ positive engagement during parent–child interaction linked their PTSD symptoms and their child's internalizing symptoms. Fathers’ and mothers’ coercive behavior toward their child linked their PTSD symptoms and their child's externalizing symptoms. Each family member's capacity for emotion regulation was associated with his or her adjustment problems at baseline. Implications for intervention, and for research using longitudinal models and a family-systems perspective of co-occurrence and cascades of symptoms across family members are described.

Child abuse is associated with a number of emotional and behavioral problems. Nevertheless, it has been argued that these adverse consequences may not hold for societies in which many of the specific acts of abuse are culturally normed. Epigenetic modifications in the genes of the hypothalamus–pituitary–adrenal axis may provide a potential mechanism translating abuse into altered gene expression, which subsequently results in behavioral changes. Our investigation took place in Tanzania, a society in which many forms of abuse are commonly employed as disciplinary methods. We included 35 children with high exposure and compared them to 25 children with low exposure. Extreme group comparisons revealed that children with high exposure reported more mental health problems. Child abuse was associated with differential methylation in the proopiomelanocortin gene (POMC), measured both in saliva and in blood. Hierarchical clustering based on the methylation of the POMC gene found two distinct clusters. These corresponded with children's self-reported abuse, with two-thirds of the children allocated into their respective group. Our results emphasize the consequences of child abuse based on both molecular and behavioral grounds, providing further evidence that acts of abuse affect children, even when culturally acceptable. Furthermore, on a molecular level, our findings strengthen the credibility of children's self-reports.

The present study utilized a multilevel approach to examine developmental trajectories in risk-taking propensity. We examined the moderating role of specific executive function components, attention shifting and inhibitory control, on the link between exuberant temperament in infancy and propensity for risk taking in childhood. Risk taking was assessed using a task previously associated with sensation seeking and antisocial behaviors. Two hundred ninety-one infants were brought into the lab and behaviors reflecting exuberance were observed at 4, 9, 24, and 36 months of age. Executive function was assessed at 48 months of age. Risk-taking propensity was measured when children were 60 months of age. The results indicated that exuberance and attention shifting, but not inhibitory control, significantly interacted to predict propensity for risk taking. Exuberance was positively associated with risk-taking propensity among children who were relatively low in attention shifting but unrelated for children high in attention shifting. These findings illustrated the multifinality of developmental outcomes for temperamentally exuberant young children and pointed to the distinct regulatory influences of different executive functions for children of differing temperaments. Attention shifting likely affords a child the ability to consider both positive and negative consequences and moderates the relation between early exuberance and risk-taking propensity.

Although the relation between child maltreatment and psychiatric impairment is well documented and preliminary evidence has linked child maltreatment with aberrant cortical connectivity of the left hemisphere, no investigations have attempted to examine these relations in the same study. Here, we examined the links among early adversity, brain connectivity, and functional outcomes. We collected resting regional EEG intra- and interhemispheric α-band (7.5–12.5 Hz) coherence and measures of general psychiatric impairment from a cohort of 38 adolescent females exposed to child maltreatment (M age = 14.47) and 24 adolescent females not exposed to child maltreatment (M age = 14.00). Maltreated youths exhibited more left hemisphere EEG coherence than the control youths, suggesting a suboptimal organization of cortical networks. Maltreated participants also showed reduced frontal (anterior) interhemispheric coherence. These differences in brain circuitry remained statistically significant even after controlling for group differences in pubertal status and socioeconomic status. Measures of functional brain connectivity were associated with several subtypes of abuse and neglect. It was important that atypical left hemisphere EEG coherence mediated the effects of child maltreatment on levels of psychiatric impairment. The findings are discussed in the context of models linking early adversity to brain function and psychopathology.

In this article we adopt the view that emotion dysregulation is characterized by emotion regulation dynamics that are defined as dysfunctional based on contextual criteria. We regard the construct of emotion regulation as valuable because it permits the integration of the classic view of emotions as interfering with human functioning and contemporary views of emotion as adaptive and beneficial. To define patterns that reflect emotion dysregulation, we explain our views of emotion as a dynamic process, and emotion regulation as the bidirectional interplay between emotions and actions/thoughts (extrinsic factors) and the contextual factors that constitute the criteria for that interplay reflecting dysregulation. This conceptualization of emotion regulation and dysregulation leads to methods for studying the intrinsic dynamics of emotion, extrinsic factors that change the intrinsic dynamics of emotion, and how emotion regulation changes over time at multiple time scales. We then apply this thinking to several emotion dysregulation patterns. Emotion regulation is a complex construct, embracing emotion as regulator and as regulated, as self- and other-regulated, and as incorporating both top-down and bottom-up regulatory processes. We highlight an emerging line of research on the development of emotion regulation in early childhood and indicate how this work can inform understanding of emotion dysregulation and the emergence of psychopathology.

Research has shown that both prenatal alcohol and tobacco exposure are associated with increased risk of significant adverse medical, developmental, and behavioral outcomes including substance abuse. Research on the outcomes of prenatal exposure to illicit drugs (PNDE) has also found increased physical and behavioral problems for gestationally drug-exposed children. However, a clear picture has not emerged on whether the consequences of PNDE are independent from those associated with having a substance abusing parent and whether PNDE increases vulnerability to drug abuse. Because of its typical co-occurrence with factors inherent in having a drug-abusing parent, PNDE is at least a marker of significant increased risk for a range of negative outcomes including greater vulnerability to substance abuse. Although a review of the relevant research literatures indicates that the direct consequences of PNDE appear to be generally both subtle and nonglobal, PNDE does appear to have negative developmental and behavioral outcomes, and there is evidence that it is a modest direct contributor to increased substance abuse vulnerability.The viewpoints expressed in this article do not necessarily represent the National Institutes of Health or the Department of Health and Human Services. The authors thank Vincent Smeriglio for the information and suggestions he provided. The views expressed in this article do not necessarily represent his views.

Adolescence is a critical period for the development of self-regulation, and peer interactions are thought to strongly influence regulation ability. Simple exposure to peers has been found to alter decisions about risky behaviors and increase sensitivity to rewards. The link between peer exposure and self-regulation is likely to vary as a function of the type and quality of peer interaction (e.g., rejection or acceptance). Little is known about how the nature of interactions with peers influences different dimensions of self-regulation. We examined how randomization to acceptance or rejection by online “virtual” peers influenced multiple dimensions of self-regulation in a multisite community sample of 273 adolescents aged 16–17 years. Compared to a neutral condition, exposure to peers produced increases in cold cognitive control, but decreased hot cognitive control. Relative to peer acceptance, peer rejection reduced distress tolerance and increased sensitivity to losses. These findings suggest that different dimensions of adolescent self-regulation are influenced by the nature of the peer context: basic cognitive functions are altered by mere exposure to peers, whereas more complex decision making and emotion regulation processes are influenced primarily by the quality of that exposure.

The aim of this paper is to clarify how neural mechanisms at the molecular level, specifically the serotonergic (5-HT) system and the hypothalamic–pituitary–adrenal axis system (HPA) in conjunction with early life stress may contribute to the emergence of aggression, self-directed and otherwise, in borderline personality disorder (BPD). Chronic dysregulation of these biological systems, which function to regulate stress and emotion, may potentiate the development of impulsive aggression in borderline personality conditions. Our central premise in this paper is that brain development, stress regulation, and early pathonomic experience are interactive and cumulative in their mutual influence on the development of impulsive aggression in BPD. We review the parameters of impulsive aggression in BPD, followed by a discussion of the neurobiological and neuroendocrine correlates of impulsive aggression with and without BPD. We then focus on the developmental continuities in BPD with attention to brain maturation of 5-HT and HPA axis function during the life span and the influence of early adverse experiences on these systems. Finally, we comment on the data of the relative stability of aggression in BPD, adolescence as a developmental stage of potential vulnerability, and the course of aggressive behavior during the life span.The authors thank Caroline Cozza, Michael McCloskey, and Kurt Knoblett for their comments during the preparation of this manuscript. This research was supported by research funding from the American Foundation of Suicide Prevention (J.K.G.), Grant MH066888-01 (R.L.), and the Borderline Personality Disorder Research Foundation (E.F.C.).

Longitudinal follow-up data for 69 very low birthweight preterm infants were used to assess the influence of four factors (neonatal medical complications, infant temperament, mother-child relationships, and family environment) on mother and teacher reports of behavior problems at 4 years. The proposed model of such influences being tested assumed that (1) the effects of neonatal medical factors would be indirect, and (2) each of the other three factors would show high stability from 1 to 4 years and would have a direct influence on behavior problem outcomes. Neither neonatal medical data nor infant-mother attachment were good predictors of behavior problems at age 4. With these exceptions, teacher report of behavior problems was predicted in a fashion consistent with the preliminary model. However, mother reports of behavior problems was predicted only by prior mother reports of child temperament. Discussion focuses on reasons for discrepancies in these pathways of influence.

Brain imaging studies in developmentally based psychopathologies most often use magnetic resonance imaging (MRI) to study regional volumes, task-related activity, neurometabolite concentrations, or the paths of fiber tracts within the brain. Methodological challenges for the use of MRI in studying these disorders include understanding the ultrastructural correlates of brain structure and function that are below the limits of resolution of this imaging modality and developing better methods for approximating the anatomical boundaries of the cytoarchitectonic units that are defined by those ultrastructural characteristics. Conceptual challenges include distinguishing findings that represent pathophysiologically central causes from compensatory and epiphenomenal effects, a difficulty that stems directly from the inherently correlational nature of imaging data. The promise of functional imaging studies must capitalize on the specificity of the cognitive and behavioral probes that are used to illuminate core features of the pathophysiology of developmental disorders, while recognizing the assumptions and limitations of the subtraction paradigms that are used to isolate the brain functions of interest. Statistical challenges include incorporating adequate statistical models for scaling effects within the brain, as well as modeling important demographic correlates that contribute to the substantial interindividual variability inherent in most imaging data. Statistical analyses need to consider the substantial intercorrelation of measures across the brain and the importance of correcting for multiple statistical comparisons, as well as the need for improved methods for brain warping and for assessing effective connectivity in functional imaging studies.

Maternal mental health during pregnancy has been linked to health outcomes in progeny. Mounting evidence implicates fetal “programming” in this process, possibly via epigenetic disruption. Maternal mental health has been associated with glucocorticoid receptor methylation (nuclear receptor subfamily 3, group C, member 1 [NR3C1]) in the neonate; however, most studies have been small (n < 100) and have failed to control for multiple testing in the statistical analysis. The Barwon Infant Study is a population-derived birth cohort with antenatal recruitment. Maternal depression and anxiety were assessed using the Edinburgh Postnatal Depression Scale and psychological distress using the Perceived Stress Scale. NR3C1 cord blood methylation levels were determined using Sequenom MassArray for 481 participants. Maternal psychological distress and anxiety were associated with a small increase in neonate NR3C1 methylation at specific CpG sites, thus replicating some previous findings. However, associations were only nominally significant and did not remain after correction for the number of CpG sites and exposures investigated. As the largest study to explore the relationship between maternal well-being and offspring NR3C1 cord blood methylation, our results highlight the need for caution when interpreting previous findings in this area. Future studies must ensure they are adequately powered to detect the likely small effect sizes while controlling for multiple testing.

This paper reviews what is known about developmental dyslexia at three levels of analysis: cognitive, neurological, and genetic. It also considers the difficult problem of establishing causal links between these levels of analysis, and argues that solving the gene–behavior problem is paradoxically easier than solving the brain–behavior problem.

A three-wave cascade model linking life stress to increases in risk behavior was tested with 347 African American emerging adults living in the rural South. Data analyses using structural equation modeling and latent growth curve modeling demonstrated that life stress was linked to increases in risk behavior as African Americans transitioned out of secondary school. The cascade model indicated that life stress fostered increases in negative emotions. Negative emotions, in turn, were linked to increases in affiliations with deviant peers and romantic partners; this forecast increases in risk behavior. The findings supported a stress proliferation framework, in which primary stressors affect increases in secondary stressors that carry forward to influence changes in risk behaviors that can potentially compromise mental health.

This study evaluated the role of attentional shifting in children's prosocial behavior with peers. Participants were 27 aggressive/rejected and 27 nonaggressive/popular kindergarten and first grade boys and girls. Children's ability to shift attention from one affective state to another was assessed during: (a) a computerized task that required shifting attention between different affective events (i.e., the Children's Attentional Shifting Task, CAST) and (b) an analogue entry task with unacquainted peers. Children's latency for sharing with peers was assessed after they experienced failure during the entry task. Aggressive/rejected children had significant difficulty shifting attention from negative to positive affect during the CAST and were slower to share after experiencing entry failure. In general, aggressive/rejected children were less able to regulate their behavior effectively after experiencing social failure. Girls, regardless of status, had less difficulty than boys shifting attention from one affective state to another during the CAST. In addition, children's social status/aggressiveness, their ability to regulate emotional behavior after social failure and to shift attention effectively on the CAST predicted approximately 31% of the variance in their latency to share. These findings suggest that the ability to shift attention between different affective states plays a significant role in children's prosocial behavior with peers.

The role of attachment in interaction with other relationships and conditions was investigated in relation to children's later psychosocial development (at ages 6 and 9). Thirty-nine unipolar depressed mothers, 24 bipolar mothers, and 32 normal control mothers and their children were studied. The network of conditions defining early experience included, in addition to attachment, maternal psychopathology, marital discord, other disordered relationships in the family, and recent losses of significant persons. Patterns of mother-child interaction were also examined. Assessments of children's problems were based on psychiatric evaluations of depressive affect, anxiety, and disruptive-oppositional behavior.

The findings support the conclusion that attachment enters into development in interaction with other relationships and conditions. Maternal psychopathology, in particular, in interaction with the attachment relationship, is linked to later developmental outcomes. The importance of considering mother-child interactional and dispositional characteristics is indicated. The early attachment relationship together with the ways in which the mother's depression is expressed with her child, and the child's style of coping with the mother's functioning establish patterns of behavior that influence the child's vulnerability to later problems. Multiple pathways of transmission of affective problems are discussed.