Prenatal exposure to maternal stress, anxiety, and depression can have lasting effects on infant development with risk of psychopathology. Although the impact of prenatal maternal distress has been well documented, the potential mechanisms through which maternal psychosocial variables shape development have yet to be fully elucidated. Advances in molecular biology have highlighted the role of epigenetic mechanisms in regulating gene activity, neurobiology, and behavior and the potential role of environmentally induced epigenetic variation in linking early life exposures to long-term biobehavioral outcomes. In this article, we discuss evidence illustrating the association between maternal prenatal distress and both fetal and infant developmental trajectories and the potential role of epigenetic mechanisms in mediating these effects. Postnatal experiences may have a critical moderating influence on prenatal effects, and we review findings illustrating prenatal–postnatal interplay and the developmental and epigenetic consequences of postnatal mother–infant interactions. The in utero environment is regulated by placental function and there is emerging evidence that the placenta is highly susceptible to maternal distress and a target of epigenetic dysregulation. Integrating studies of prenatal exposures, placental function, and postnatal maternal care with the exploration of epigenetic mechanisms may provide novel insights into the pathophysiology induced by maternal distress.

The short allele of the serotonin transporter linked polymorphic region (5-HTTLPR) moderates the effects of stress on vulnerability to mood and anxiety disorders. The mechanism by which this occurs may relate to differential sensitivity to stressful life events. Here we explored whether 5-HTTLPR and sex affected behavioral responses to repeated maternal separation in infant rhesus macaques. Behaviors were collected during the acute (Day 1) and the chronic (Days 2–4) phases of the separation, and the effects of duration of separation (acute vs. chronic), genotype (long/long vs. short allele), and sex (male vs. female) on behavioral responses were analyzed across four successive separations. Males increased their levels of locomotion with repeated maternal separation, whereas females exhibited an increase in frequency of self-directed behavior, a measure of “depression-like” behavior. The short-allele predicted increased environmental exploration, particularly during the chronic phase of social separation, indicative of higher arousal. In addition, the short-allele carriers were more likely to increase their levels of self-directed behavior during the chronic phase of separation, as a function of repeated exposures. These findings suggest that the short allele may increase reactivity to repeated, chronic stressors, leaving them more vulnerable to affective psychopathology, with females particularly vulnerable.

Investigators have identified a number of factors that increase the risk for experiencing sexual coercion, but as yet little is known about how sexual coercion in turn affects these risk factors. Using a sample of 110 adolescents, the current study examined the hypothesis that, after an incident of sexual coercion, adolescents would exhibit increases in several behaviors known to increase risk for victimization. As predicted, after experiencing sexual coercion, adolescents reported increased externalizing symptoms, more frequent sexual intercourse and a greater total number of intercourse partners. Finally, alcohol use, drug use, and problems related to substance use increased. These findings suggest the presence of a feedback loop, in which the experience of sexual coercion leads to an intensification of the factors that initially contributed risk for coercion.

This study was designed to examine the prospective relations of life stress and genetic status with increases in drug use. African Americans (N = 399) in rural Georgia (Wave 1 mean age = 17 years) provided three waves of data across 27.5 months and a saliva sample from which the dopamine receptor D4 (DRD4) gene was genotyped. Multilevel growth curve modeling analysis indicated that emerging adults manifested the highest escalations in drug use when they reported high life stress and carried an allele of DRD4 with 7 or more repeats (7 + R allele). In addition, emerging adults who reported high life stress and carried the 7 + R allele evinced the largest increases in two proximal risk factors for drug use: affiliations with drug-using companions and drug use vulnerability cognitions. Furthermore, when the Gene × Environment interaction effects on the increases in affiliations with drug-using companions and vulnerability cognitions were entered into the model forecasting drug use, the Life Stress × DRD4 Status interaction on drug use became nonsignificant in the presence of the risk mechanisms. This finding provides an example of “second generation” Gene × Environment interaction research in which the interaction's effects on proximal risk mechanisms account for its effects on outcomes.

The period of in utero development is one of the most critical windows during which adverse intrauterine conditions and exposures can influence the growth and development of the fetus as well as the child's future postnatal health and behavior. Maternal cigarette smoking during pregnancy remains a relatively common but nonetheless hazardous in utero exposure. Previous studies have associated prenatal smoke exposure with reduced birth weight, poor developmental and psychological outcomes, and increased risk for diseases and behavioral disorders later in life. Researchers are now learning that many of the mechanisms whereby maternal smoke exposure may affect key pathways crucial for proper fetal growth and development are epigenetic in nature. Maternal cigarette smoking during pregnancy has been associated with altered DNA methylation and dysregulated expression of microRNA, but a deeper understanding of the epigenetics of maternal cigarette smoking during pregnancy as well as how these epigenetic changes may affect later health and behavior remain to be elucidated. This article seeks to explore many of the previously described epigenetic alterations associated with maternal cigarette smoking during pregnancy and assess how such changes may have consequences for both fetal growth and development, as well as later child health, behavior, and well-being. We also outline future directions for this new and exciting field of research.

This study examined the interplay between the influence of peers who promote alcohol use and μ-opioid receptor M1 (OPRM1) genetic variation in the intergenerational transmission of alcohol use disorder (AUD) symptoms while separating the “traitlike” components of AUD symptoms from their age-specific manifestations at three ages from emerging adulthood (17–23 years) to adulthood (29–40 years). The results for males were consistent with genetically influenced peer selection mechanisms as mediators of parent alcoholism effects. Male children of alcoholics were less likely to be carriers of the G allele in single nucleotide polymorphism A118G (rs1799971), and those who were homozygous for the A allele were more likely to affiliate with alcohol use promoting peers who increased the risk for AUD symptoms at all ages. There was evidence for women of an interaction between OPRM1 variation and peer affiliations but only at the earliest age band. Peer influences had stronger effects among women who were G-carriers. These results illustrate the complex ways in which the interplay between influences at multiple levels of analysis can underlie the intergenerational transmission of alcohol disorders as well as the importance of considering age and gender differences in these pathways.

A comparison of offspring of parents with bipolar disorder (OBD) and offspring of parents with no mental disorder (ONMD) showed that parents' neuroticism was associated with internalizing and externalizing problems among their children. The present study examined whether parents' neuroticism predicted poor interpersonal functioning among offspring 10 years later and whether the problems observed in middle childhood mediated the association between parents' neuroticism and offspring functioning. When offspring were in middle childhood, parents completed the revised NEO Personality Inventory and rated the child's behavior on the Child Behavior Checklist. Ten years later, 65 OBD and 59 ONMD completed interviews assessing mental disorders and interpersonal and noninterpersonal functioning. High neuroticism and low agreeableness in parents predicted poor interpersonal functioning in their offspring in late adolescence–early adulthood. The offspring's externalizing and internalizing problems in middle childhood partially mediated the association between parents' personality and offspring interpersonal functioning. Moreover, the association between parents' neuroticism and offspring internalizing problems was stronger among the OBD than the ONMD. Overall, the results suggested an intergenerational transmission of risk whereby high neuroticism and low agreeableness in parents were associated with behavioral problems among offspring in middle childhood that, in turn, predicted poor interpersonal functioning 10 years later.

The current study examines the interplay between parental overreactivity and children's genetic backgrounds as inferred from birth parent characteristics on the development of negative emotionality during infancy, and in turn, to individual differences in externalizing problems in toddlerhood. The sample included 361 families linked through adoption (birth parents and adoptive families). Data were collected when the children were 9, 18, and 27 months old. Results indicated links between individual levels and changes in negative emotionality during infancy and toddlerhood to externalizing problems early in the third year of life. Findings also revealed an interaction between birth mother negative affect and adoptive mother overreactive parenting on children's negative emotionality. This Genotype × Environment interaction predicted externalizing problems indirectly through its association with negative emotionality and revealed stronger effects of genetic risk for children with less overreactive parenting from their mothers. Limitations of this study and directions for future research are discussed.

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.

Building on Roisman, Fraley, and Belsky, who produced evidence for two modestly correlated dimensions (i.e., dismissing and preoccupied states of mind) underlying individual differences in attachment as assessed by the Adult Attachment Interview using the Main and Goldwyn classification system, this report replicates and extends relevant evidence in a large sample of adults (N = 842) who completed the Adult Attachment Interview coded using Kobak's Adult Attachment Interview Q-Sort. Principal components analysis of item-level Q-Sort data yielded two state of mind (dismissing vs. free to evaluate and preoccupied vs. not) and two inferred experience (maternal and paternal) components that were associated with two domains of theoretical significance to attachment theory: interpersonal functioning in a romantic context and symptoms of psychopathology. Results revealed distinctive behavioral correlates of dismissing versus preoccupied states of mind and emphasize the differential predictive significance for developmental adaptation of attachment states of mind versus adults' recollections of their early experiences. Implications for adult attachment methodology and theory are discussed.

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.

An overview is provided of recent twin, molecular genetic, and magnetic resonance imaging studies that are helping to inform a model of developmental vulnerability to adult psychopathy. Although the current evidence base suggests that children with high levels of callous–unemotional traits are genetically and neurocognitively vulnerable to developing psychopathic and antisocial behaviors, existing research also clearly indicates that environmental influences play an important role. One potential implication is that interventions for children with antisocial behavior and callous–unemotional traits may need to be tailored to take into account their distinct pattern of neurocognitive vulnerability, as revealed by developmental neuroimaging studies. Specifically, interventions that pursue punishment-oriented or explicit empathy induction strategies may be less effective with this group of antisocial children. By contrast, preliminary evidence suggests that enhancing positive parenting and parental involvement, as well as applying consistent rewards may represent more promising intervention approaches.

Vibrant expression of emotion is the principal means infants and young children use to elicit appropriate and timely caregiving, stimulation, and support. This study examined the depression–inhibition hypothesis: that declines in mothers' support as their depressive symptoms increase inhibit children's emotional communication. Ninety-four mothers and their 14- to 27-month-olds interacted in a university playroom. Based on microanalytic coding of discrete facial displays, results supported three components of the hypothesis. (a) As mothers' depressive symptoms increased, children displayed less facial emotion (more flat affect, less joy, less sadness, less negative). (b) Mothers' low emotional and behavioral support predicted children's low facial communication and mediated relations between mothers' depressive symptoms and children's infrequent emotion. (c) Children who were passive with mothers behaviorally expressed emotion infrequently. Children's passivity mediated relations between mothers' depressive symptoms and children's infrequent emotion displays. Contrary to modeling and contagion theories, mothers' facial displays did not mediate relations between their depressive symptoms and children's facial displays. Nor were the outcomes children experienced regulating their facial displays. Rather, findings suggest that, even when depressive symptoms are modest, young children inhibit emotion as mothers' depressive symptoms increase to withdraw from unresponsive mothers, which may adversely affect children's subsequent relationships and competencies.

Early onset aggression precipitates a cascade of risk factors, increasing the probability of a range of externalizing and internalizing psychopathological outcomes. Unfortunately, decades of research on the etiological contributions to the manifestation of aggression have failed to yield identification of any risk factors determined to be either necessary or sufficient, likely attributable to etiological heterogeneity within the construct of aggression. Differential pathways of etiological risk are not easily discerned at the behavioral or self-report level, particularly in young children, requiring multilevel analysis of risk pathways. This study focuses on three domains of risk to examine the heterogeneity in 207 urban kindergarten children with high levels of aggression: cognitive processing, socioemotional competence and emotion processing, and family context. The results indicate that 90% of children in the high aggression group could be characterized as either low in verbal ability or high in physiological arousal (resting skin conductance). Children characterized as low verbal, high arousal, or both differed in social and emotional competence, physiological reactivity to emotion, and aspects of family-based contextual risk. The implications of this etiologic heterogeneity of aggression are discussed in terms of assessment and treatment.

We used a 3-year cross-sequential longitudinal design to examine the relations between self-efficacy judgments in three different domains (academic, social, resisting negative peer influences), cultural identity, theories of intelligence, and depressive symptoms. One hundred ninety-eight American Indian youths participated in the study, who all attended a middle school on a reservation in the northern plains of the United States. We conducted multilevel models to examine both between- and within-person associations as well as to investigate lagged within-youth associations. We found that not only did youths with relatively high self-efficacy have lower depressive symptom levels than other youths, but also increases in efficacy beliefs for academic, social, and for resisting negative peer influences predicted decreases in depressive symptoms within youths, even after controlling for previous levels of depressive symptoms as well as both contemporaneous and previous academic achievement. Neither cultural identity nor theories of intelligence moderated the relationship between self-efficacy and depression. As the first evidence that within-youth improvements in self-efficacy has developmental benefits, our findings help fill a long empty niche in the line of studies investigating the impact of efficacy beliefs on depressive symptoms.

Child neglect is the most prevalent form of child maltreatment in the United States, and poses a serious public health concern. Children who survive such episodes go on to experience long-lasting psychological and behavioral problems, including higher rates of post-traumatic stress disorder symptoms, depression, alcohol and drug abuse, attention-deficit/hyperactivity disorder, and cognitive deficits. To date, most research into the causes of these life-long problems has focused on well-established targets such as stress responsive systems, including the hypothalamus–pituitary–adrenal axis. Using the maternal separation and early weaning model, we have attempted to provide comprehensive molecular profiling of a model of early-life neglect in an organism amenable to genomic manipulation: the mouse. In this article, we report new findings generated with this model using chromatin immunoprecipitation sequencing, diffuse tensor magnetic resonance imaging, and behavioral analyses. We also review the validity of the maternal separation and early weaning model, which reflects behavioral deficits observed in neglected humans including hyperactivity, anxiety, and attentional deficits. Finally, we summarize the molecular characterization of these animals, including RNA profiling and label-free proteomics, which highlight protein translation and myelination as novel pathways of interest.

Empathy dysfunction is one of the core characteristics of youth with callous–unemotional (CU) traits. How such a dysfunction is associated with abnormal neural processing, however, remains to be determined. This study combined assessment of Hare Psychopathy Checklist Youth Version, pressure pain threshold, and event-related brain potentials elicited by the perception of people in pain in 15 young offenders with low CU traits (LCU), 13 with high CU traits (HCU), and 15 typically developing controls. Compared to the controls, LCU and HCU had higher pain thresholds. Although only the central late positive potential (LPP) was reduced in LCU, both the frontal N120 and central LPP were diminished in HCU. When exposed to situations in which someone was harmed by another, HCU retained the LPP, and this response was significantly correlated with their psychopathic traits and pain thresholds. Both groups had no deficit in sensorimotor resonance as assessed by mu suppression. These results demonstrate that youth with HCU exhibit atypical neural dynamics of pain empathy processing in the early stage of affective arousal, which is coupled with their relative insensitivity to actual pain. Their capacity to understand intentionality, however, was not affected. Such uncoupling between affective arousal and emotion understanding may contribute to instigating aggressive behaviors in juvenile psychopaths.

During the last quarter century, developmental psychopathology has become increasingly inclusive and now spans disciplines ranging from psychiatric genetics to primary prevention. As a result, developmental psychopathologists have extended traditional diathesis–stress and transactional models to include causal processes at and across all relevant levels of analysis. Such research is embodied in what is known as the multiple levels of analysis perspective. We describe how multiple levels of analysis research has informed our current thinking about antisocial and borderline personality development among trait impulsive and therefore vulnerable individuals. Our approach extends the multiple levels of analysis perspective beyond simple Biology × Environment interactions by evaluating impulsivity across physiological systems (genetic, autonomic, hormonal, neural), psychological constructs (social, affective, motivational), developmental epochs (preschool, middle childhood, adolescence, adulthood), sexes (male, female), and methods of inquiry (self-report, informant report, treatment outcome, cardiovascular, electrophysiological, neuroimaging). By conducting our research using any and all available methods across these levels of analysis, we have arrived at a developmental model of trait impulsivity that we believe confers a greater understanding of this highly heritable trait and captures at least some heterogeneity in key behavioral outcomes, including delinquency and suicide.

In recent years, translational research involving humans and animals has uncovered biological and physiological pathways that explain associations between early adverse circumstances and long-term mental and physical health outcomes. In this article, we summarize the human and animal literature demonstrating that epigenetic alterations in key biological systems, the hypothalamus–pituitary–adrenal axis and immune system, may underlie such disparities. We review evidence suggesting that changes in DNA methylation profiles of the genome may be responsible for the alterations in hypothalamus–pituitary–adrenal axis and immune system trajectories. Using some preliminary data, we demonstrate how explorations of genome-wide and candidate-gene DNA methylation profiles may inform hypotheses and guide future research efforts in these areas. We conclude our article by discussing the many important future directions, merging perspectives from developmental psychology, molecular genetics, neuroendocrinology, and immunology, that are essential for furthering our understanding of how early adverse circumstances may shape developmental trajectories, particularly in the areas of stress reactivity and physical or mental health.

The study examined the interaction between early maturational timing (measured by premature adrenarche [PA]) and executive functioning and cortisol reactivity on symptoms of psychopathology. The study included 76 girls aged 6 through 8 years (mean = 7.50, SD = 0.85) with PA (n = 40) and on-time adrenarche (n = 36). Girls completed a battery of psychological and neuropsychological tests and blood sampling for cortisol. Parents completed the Child Behavior Checklist. The results demonstrated that girls with PA with lower levels of executive functioning had higher externalizing and anxious symptoms compared to other girls. In addition, girls with PA who demonstrated increases in serum cortisol had higher externalizing symptoms than those with stable patterns. Finally, girls with PA who demonstrated decreases in cortisol reported higher depressive symptoms. The findings from this study provide important information concerning the impact of cognitive functioning and stress reactivity on adjustment to early maturation in girls with PA. The results of this research may inform screening and intervention efforts for girls who may be at greatest risk for emotional and behavioral problems as a result of early maturation.