Our findings in the Helsinki Influenza Study and the Danish Forty Year Study lead us to conclude that a 2nd-trimester maternal influenza infection may increase risk for adult schizophrenia or adult major affective disorder. More recently we have also reported an increase of unipolar depression among offspring who were exposed prenatally to a severe earthquake (7.8 on the Richter scale) in Tangshan, China. Among the earthquake-exposed males (but not the females), we observed a significantly greater depression response for those individuals exposed during the 2nd trimester of gestation. These findings suggest that maternal influenza infection and severe maternal stress may operate (in different ways) as teratogens, disrupting the development of the fetal brain and increasing risk for developing schizophrenia or depression in adulthood.

As studies of measured gene–environment interactions (G × E) in developmental psychopathology gain momentum, methods for systematically and quantitatively summarizing effects across multiple studies are urgently needed. Meta-analyses of G × E findings are critical for evaluating the overall statistical and theoretical significance of any given G × E based on cumulative and systematically combined knowledge. Although meta-analytic methods for the combination of study findings based on single effect measures such as odds ratios and mean differences are well established, equivalent methods for the meta-analysis of studies investigating interactions are not well developed. This article describes one simple approach to the meta-analysis of G × E effects using, as a contemporaneous example, the interaction of the monoamine oxidase A (MAOA) gene and the impact of childhood maltreatment on risk for developing antisocial behavior.

In this investigation, gene–environment interaction effects in predicting resilience in adaptive functioning among maltreated and nonmaltreated low-income children (N = 595) were examined. A multicomponent index of resilient functioning was derived and levels of resilient functioning were identified. Variants in four genes (serotonin transporter linked polymorphic region, corticotropin releasing hormone receptor 1, dopamine receptor D4–521C/T, and oxytocin receptor) were investigated. In a series of analyses of covariance, child maltreatment demonstrated a strong negative main effect on children's resilient functioning, whereas no main effects for any of the genotypes of the respective genes were found. However, gene–environment interactions involving genotypes of each of the respective genes and maltreatment status were obtained. For each respective gene, among children with a specific genotype, the relative advantage in resilient functioning of nonmaltreated compared to maltreated children was stronger than was the case for nonmaltreated and maltreated children with other genotypes of the respective gene. Across the four genes, a composite of the genotypes that more strongly differentiated resilient functioning between nonmaltreated and maltreated children provided further evidence of genetic variations influencing resilient functioning in nonmaltreated children, whereas genetic variation had a negligible effect on promoting resilience among maltreated children. Additional effects were observed for children based on the number of subtypes of maltreatment children experienced, as well as for abuse and neglect subgroups. Finally, maltreated and nonmaltreated children with high levels of resilience differed in their average number of differentiating genotypes. These results suggest that differential resilient outcomes are based on the interaction between genes and developmental experiences.

Trajectories of relational aggression were examined in a large, diverse sample of fourth-grade students. Hierarchical linear modeling was used to examine relational aggression over 1 calendar year. The results indicated that relational aggression increased in a linear fashion for girls over the course of the study. In addition, increases in friend intimate exchange were associated with time-dependent increases in relational aggression among girls only. Relational aggression and internalizing “tracked” together across the course of the study. Overall, the findings suggest relational aggression becomes increasingly common among elementary school girls, and girls' close, dyadic relationships may fuel relationally aggressive behavior in some contexts. Finally, the results indicate that relational aggression trajectories are dynamically associated with maladjustment.This study was funded by grants from NIMH (MH63684) and NSF (BCS-0126521) to N. C. Crick. Preparation of this manuscript was supported by a NIMH Traineeship (MH-15755) to D. Murray-Close and J. M. Ostrov. Portions of this manuscript were presented at the 2004 Biennial Meeting of The Society for Research on Adolescence, Baltimore, MD. We thank Kathleen E. Woods for her assistance and comments on an earlier draft, Dr. Jeff Long for his statistical consultation and assistance with this study, and Peter Ralston and the entire School Buddies Project team for assistance with the collection of this data. Finally, we thank the principals, teachers, parents, and children for their participation.

Childhood adversity is associated with increased risk for psychopathology. Neurodevelopmental pathways underlying this risk remain poorly understood. A recent conceptual model posits that childhood adversity can be deconstructed into at least two underlying dimensions, deprivation and threat, that are associated with distinct neurocognitive consequences. This model argues that deprivation (i.e., a lack of cognitive stimulation and learning opportunities) is associated with poor executive function (EF), whereas threat is not. We examine this hypothesis in two studies measuring EF at multiple levels: performance on EF tasks, neural recruitment during EF, and problems with EF in daily life. In Study 1, deprivation (low parental education and child neglect) was associated with greater parent-reported problems with EF in adolescents (N = 169; 13–17 years) after adjustment for levels of threat (community violence and abuse), which were unrelated to EF. In Study 2, low parental education was associated with poor working memory (WM) performance and inefficient neural recruitment in the parietal and prefrontal cortex during high WM load among adolescents (N = 51, 13–20 years) after adjusting for abuse, which was unrelated to WM task performance and neural recruitment during WM. These findings constitute strong preliminary evidence for a novel model of the neurodevelopmental consequences of childhood adversity.

There is clear evidence that the mother's stress, anxiety, or depression during pregnancy can alter the development of her fetus and her child, with an increased risk for later psychopathology. We are starting to understand some of the underlying mechanisms including the role of the placenta, gene–environment interactions, epigenetics, and specific systems including the hypothalamic–pituitary–adrenal axis and cytokines. In this review we also consider how these effects may be different, and potentially exacerbated, in different parts of the world. There can be many reasons for elevated prenatal stress, as in communities at war. There may be raised pregnancy-specific anxiety with high levels of maternal and infant death. There can be raised interpersonal violence (in Afghanistan 90.2% of women thought that “wife beating” was justified compared with 2.0% in Argentina). There may be interactions with nutritional deficiencies or with extremes of temperature. Prenatal stress alters the microbiome, and this can differ in different countries. Genetic differences in different ethnic groups may make some more vulnerable or more resilient to the effects of prenatal stress on child neurodevelopment. Most research on these questions has been in predominantly Caucasian samples from high-income countries. It is now time to understand more about prenatal stress and psychopathology, and the role of both social and biological differences, in the rest of the world.

Study I examined relationships between an interview measure of children's future expectations and variables reflecting self-system functioning with 136 9–11-year-old urban children exposed to high psychosocial stress. As expected, future expectations related to affect regulation, self-representations, and school adjustment. Study II, done with a subsample of the original group, showed that early positive future expectations predicted enhanced socioemotional adjustment in school and a more internal locus of control 2½–3½ years later and acted as a protective factor in reducing the negative effects of high stress on self-rated competence. These findings: (a) are consistent with prior data showing positive expectations to be characteristic of resilient children; (b) suggest that early positive future expectations influence later adjustment; and (c) underscore the role children have in actively structuring their environments and, thus, influencing their development. The heuristic value of the construct of self for future studies of resilience is suggested, and implications for preventive interventions are considered.

Although personality disorders are best understood in the context of lifetime development, there is a paucity of work examining their longitudinal trajectory. An understanding of the expected course and the genetic and environmental contributions to these disorders is necessary for a detailed understanding of risk processes that lead to their manifestation. The current study examined the longitudinal course and heritability of borderline personality disorder (BPD) over a period of 10 years starting in adolescence (age 14) and ending in adulthood (age 24). In doing so, we built on existing research by using a large community sample of adolescent female twins, a sensitive dimensional measure of BPD traits, an extended follow-up period, and a longitudinal twin design that allowed us to investigate the heritability of BPD traits at four discrete ages spanning midadolescence to early adulthood. Results indicated that mean-level BPD traits significantly decline from adolescence to adulthood, but rank order stability remained high. BPD traits were moderately heritable at all ages, with a slight trend for increased heritability from age 14 to age 24. A genetically informed latent growth curve model indicated that both the stability and change of BPD traits are highly influenced by genetic factors and modestly by nonshared environmental factors. Our results indicate that as is the case for other personality dimensions, trait BPD declines as individuals mature from adolescence to adulthood, and that this process is influenced in part by the same genetic factors that influence BPD trait stability.

A model of asymmetric contributions to the control of different subcomponents of approach- and withdrawal-related emotion and psychopathology is presented. Two major forms of positive affect are distinguished. An approach-related form arises prior to goal attainment, and another form follows goal attainment. The former is hypothesized to be associated with activation of the left prefrontal cortex. Individual differences in patterns of prefrontal activation are stable over time. Hypoactivation in this region is proposed to result in approach-related deficits and increase an individual's vulnerability to depression. Data in support of these proposals are presented. The issue of plasticity is then considered from several perspectives. Contextual factors are superimposed upon tonic individual differences and modulate the magnitude of asymmetry. Pharmacological challenges also alter patterns of frontal asymmetry. A diverse array of evidence was then reviewed that lends support to the notion that these patterns of asymmetry may be importantly influenced by early environmental factors that result in enduring changes in brain function and structure.

High rates of comorbidity are observed between internalizing and externalizing problems, yet the developmental dynamics of comorbid symptom presentations are not yet well understood. This study explored the developmental course of latent profiles of internalizing and externalizing symptoms across kindergarten, first grade, and second grade. The sample consisted of 336 children from an urban, low-income community, selected based on relatively high (61%) or low (39%) aggressive/oppositional behavior problems at school entry (64% male; 70% African American, 20% Hispanic). Teachers reported on children's symptoms in each year. An exploratory latent profile analysis of children's scores on aggression/oppositionality, hyperactivity/inattention, anxiety, and social withdrawal symptom factors revealed four latent symptom profiles: comorbid (48% of the sample in each year), internalizing (19%–23%), externalizing (21%–22%), and well-adjusted (7%–11%). The developmental course of these symptom profiles was examined using a latent transition analysis, which revealed remarkably high continuity in the comorbid symptom profile (89% from one year to the next) and moderately high continuity in both the internalizing and externalizing profiles (80% and 71%, respectively). Internalizing children had a 20% probability of remitting to the well-adjusted profile by the following year, whereas externalizing children had a 25% probability of transitioning to the comorbid profile. These results are consistent with the hypothesis that a common vulnerability factor contributes to developmentally stable internalizing–externalizing comorbidity, while also suggesting that some children with externalizing symptoms are at risk for subsequently accumulating internalizing symptoms.

The model presented identifies the importance of neural regulation of autonomic state as an antecedent substrate for emotional, cognitive, and behavioral regulation. It is proposed that individual differences in neural regulation of autonomic state are related to normal and abnormal development. Establishing nervous system regulation of autonomic state is the infant's initial task of self-regulation. Survival for the high-risk infant is based primarily on physiological self-regulation. Although the methods described focus on the high-risk neonate, the model provides insight into normal development and may be generalized to the study of older children and adults with behavioral and psychological problems. Moreover, the model may contribute to assessment and intervention strategics for normal and abnormal development.

This paper presents single-subject analyses of newly developing attachment relationships in 10 foster infant–caregiver dyads. Using a diary methodology, at least 2 months of daily data were provided by foster parents on infants' attachment behaviors. Foster infant attachment was also assessed using the Strange Situation. Foster mother state of mind regarding attachment was measured using the Adult Attachment Interview. For eight infants, diary data revealed predominant patterns of attachment behavior emerging within 2 months of placement. In most cases, diary data predicted Strange Situation classifications. Both Strange Situation and diary data indicated that the three children placed in foster care before 12 months of age with foster parents having primary or secondary autonomous states of mind were classified as having secure attachments. The five children placed after 12 months of age showed predominantly insecure attachment behavior in the diary and were classified as insecure in the Strange Situation. Contingency analyses of behavioral sequences reported in the diary revealed that foster parents tended to complement their foster childrens' attachment behaviors.

The concepts of allostatic load and allostatic processes can help psychologists understand how health trajectories are influenced by stressful childhood experiences in the family. This paper describes psychological pathways and two key allostatic mediators, the hypothalamic–pituitary–adrenal axis and the immune system, through which stressful early rearing conditions may influence adult mental and physical health. The action of meshed gears is introduced as a metaphor to illustrate how responses occurring within a brief time frame, for example, immediate reactions to stressors, can influence developmental and health processes unfolding over much longer spans of time. We identify early-developing psychological and biological response patterns that could link chronic stressors in childhood to later health outcomes. Some of these “precursor outcomes” (e.g., heightened vigilance and preparedness for threats; enhanced inflammatory and humoral responses to infectious microorganisms) appear to be aimed at protection from immediate dangers; they may reflect “adaptive trade-offs” that balance short-term survival advantages under harsh rearing conditions against disadvantages manifested later in development. Our analysis also suggests mechanisms that underlie resilience in risky family environments.

This study investigated the development of attachment relationships in 38 foster infant–caregiver dyads over the first 2 months of placement. We used the Parent Attachment Diary to measure foster infants' daily attachment behaviors, the Adult Attachment Interview to examine foster parents' attachment states of mind, and Ainsworth's Strange Situation to capture attachment classifications. We examined differences in diary scales (secure, avoidant, resistant, and coherence) as they related to age at placement and foster parent attachment, using hierarchical linear modeling and analyses of variance. The results indicated infants with autonomous foster parents and infants placed at younger ages showed higher early and overall levels of secure behavior, less avoidant behavior, and more coherent attachment strategies compared to infants placed with nonautonomous foster parents. Changes in attachment behaviors over time were not predicted by the models; however, there was a significant decrease in the daily coherence of attachment behaviors associated with Strange Situation disorganization. Finally, we found significant concordance between the diary and Strange Situation scales for secure and avoidant behaviors.This research is part of an ongoing study of infants in foster care conducted at the University of Delaware in collaboration with the Baltimore City Department of Social Services and Delaware Department of Family Services. This study was supported by a grant from the National Institute of Mental Health (R0152135) to the second author. We acknowledge the help of Kathleen Albus and Brady Bates with this project. Thanks are also due to Doris Loftin, Beverly Williams, and Gerri Robinson of the Baltimore City Department of Social Services, as well as John Bates, Darlene Lantz, and Kathy Way of the Delaware Division of Children, Youth, and Their Families. Our deepest gratitude is expressed to the caseworkers, foster families, and children at both agencies.

The study of clearly identifiable patterns of atypical development can inform normal development in significant ways. Delayed or deviant development puts in high relief not only the sequence of development but also the individual components. This article presents the results of studies that compare adolescents with Williams syndrome, a rare metabolic neurodevelopmental disorder resulting in mental retardation, with cognitively matched adolescents with Down syndrome. We investigate the interaction between affect and language through storytelling. In contrast to the adolescents with Down syndrome, the Williams syndrome subjects tell coherent and complex narratives that make extensive use of affective prosody. Furthermore, stories from the Williams but not the Down subjects are infused with lexically encoded narrative evaluative devices that enrich the referential content of the stories. This contrast in expressivity between two matched atypical groups provides an unusual perspective on the underlying structure of the social cognitive domain.

Eighty-two mother–infant dyads, comprising women with psychiatric disorder and individually matched controls, were followed up over the children's 1st year of life. The mothers with mental illness consisted of two subgroups: first, 25 severely mentally ill mothers who had been admitted to a psychiatric unit with their infants; and second, 16 mothers from a community sample meeting research diagnostic criteria for unipolar, nonpsychotic depression. With the exception of six dyads in the in-patient group, observations were made of the mother–infant interaction and the quality of the infant–mother attachment relationship at 12 months. The nature and course of the mothers' illness was also documented. Although few residual symptoms of maternal mental illness were detected at 1 year postpartum, interactional disturbances were evident among the case group dyads. A strong association was revealed between infant–mother attachment quality and maternal diagnosis: a manic episode of illness in the postpartum period was related to security in the attachment relationship, and psychotic or nonpsychotic depression was related to insecurity. Concurrent patterns of mother–infant interaction provided support for this finding.

Postinstitutionalized children frequently demonstrate persistent socioemotional difficulties. For example, some postinstitutionalized children display an unusual lack of social reserve with unfamiliar adults. This behavior, which has been referred to as indiscriminate friendliness, disinhibited attachment behavior, and disinhibited social behavior, was examined by comparing children internationally adopted from institutional care to children internationally adopted from foster care and children raised by their biological families. Etiological factors and behavioral correlates were also investigated. Both groups of adopted children displayed more disinhibited social behavior than the nonadopted children. Of the etiological factors examined, only the length of time in institutional care was related to disinhibited social behavior. Disinhibited social behavior was not significantly correlated with general cognitive ability, attachment-related behaviors, or basic emotion abilities. However, this behavior was negatively associated with inhibitory control abilities even after controlling for the length of time in institutional care. These results suggest that disinhibited social behavior might reflect underlying deficits in inhibitory control.

Peer relationship difficulties and peer rejection are common in youngsters with attention-deficit hyperactivity disorder (ADHD), mandating focus on assessment issues, underlying reasons for peer approval and disapproval, links with comorbid aggression, and the mediating role of sociocognitive mechanisms as well as emotion regulation strategies. With previously unfamiliar ADHD and comparison boys who attended naturalistic summer research programs, we found the following: (a) parent and teacher estimates (but not self-reports) showed moderate correspondence with peer-nominated social preference; (b) ADHD boys were more likely than their comparison peers to accept other ADHD agemates; (c) aggression and noncompliance Predominated as self-reported reasons for rejecting agemates in both ADHD and comparison groups, with Perceived similarity the chief mediator of peer acceptance; (d) the high-aggressive subgroup of ADHD boys showed markedly worse peer sociometric status than did ADHD boys without aggression, for whom social isolation was also a predictor of peer reputation; and (e) self-reported social goals of a sensation-seeking nature and observed emotional reactivity characterized high-aggressive boys with ADHD and predicted end-of-program peer disapproval. We discuss implications for normal developmental processes and for intervention efforts.

Most contemporary accounts of psychopathology acknowledge the importance of both biological and environmental influences on behavior. In developmental psychopathology, multiple etiological mechanisms for psychiatric disturbance are well recognized, including those operating at genetic, neurobiological, and environmental levels of analysis. However, neuroscientific principles are rarely considered in current approaches to prevention or intervention. In this article, we explain why a deeper understanding of the genetic and neural substrates of behavior is essential for the next generation of preventive interventions, and we outline 10 specific reasons why considering biological processes can improve treatment efficacy. Among these, we discuss (a) the role of biomarkers and endophenotypes in identifying those most in need of prevention; (b) implications for treatment of genetic and neural mechanisms of homotypic comorbidity, heterotypic comorbidity, and heterotypic continuity; (c) ways in which biological vulnerabilities moderate the effects of environmental experience; (d) situations in which Biology × Environment interactions account for more variance in key outcomes than main effects; and (e) sensitivity of neural systems, via epigenesis, programming, and neural plasticity, to environmental moderation across the life span. For each of the 10 reasons outlined we present an example from current literature and discuss critical implications for prevention.

Adolescents' susceptibility to peer influence was examined as a marker of difficulties in the general process of autonomy development that was likely to be related to deficits across multiple domains of psychosocial functioning. A laboratory-based assessment of susceptibility to peer influence in interactions with a close friend was developed and examined in relation to corollary reports obtained from adolescents, their mothers, and close peers at ages 13 and 14. As hypothesized, observed susceptibility to peer influence with a close friend predicted future responses to negative peer pressure, but it was also related to broader markers of problems in functioning, including decreases in popularity, and increasing levels of depressive symptoms, over time. Susceptibility to peer influence was also linked to higher concurrent levels of substance use, externalizing behavior, and sexual activity. Results are interpreted as reflecting the central role of establishing autonomy with peers in psychosocial development.This study was supported by grants from the National Institute of Mental Health (R01-MH44934 and R01-MH58066).