There is increasing interest in the psychosocial variables that might predict the course of child and adolescent bipolar disorder. In the literature on adult bipolar disorder, life events have been shown to be a major predictor of symptoms. In this review, we focus on studies of how life events influence the course of child and adolescent bipolar disorder. To begin, we review methodological considerations in life events research, and briefly summarize the findings regarding life events in adult bipolar disorder. Then, we discuss available studies on life events as a predictor of the course of juvenile bipolar disorder. We conclude with suggested directions for future research.

The association between young adolescents' psychological profiles and their subsequent adjustment was examined in a sample of 606 adolescents (ages 12–13) drawn from the mother–child data set of the National Longitudinal Survey of Youth. Cluster analysis was used to identify distinct groups of youth based on self-regulation, proneness to risk, self-worth, and perceived academic competence. Five replicable clusters were identified corresponding to optimal, average, behavioral risk, low self-regulation, and emotional risk groups. These clusters were associated with distinct patterns of adjustment 4 years later. At ages 16–17, youth in the optimal group tended to report better academic performance, less problem behavior, and less depression than youth in the three risk groups; however, their functioning did not differ significantly from youth in the average group. The three risk groups differed in self-reported depression symptoms and academic performance but not in levels of problem behavior. Differences among the five groups persisted when demographic and contextual variables were controlled. These results support the existence of different groups of youth who follow distinct developmental trajectories and may experience different patterns of adjustment.This research was funded by a grant to M. Raffaelli and L. Crockett from the National Institute of Mental Health (R01-MH62977). We thank Rebecca Colman, Yuh-Ling Shen, Sam Hardy, Rebecca Goodvin, Myesha Albert, Andy Peytchev, Jenenne Geske, Jennifer Bowers, Devan Starks, and Brett Avila for their contributions to the project. We also thank Cal Garbin for his statistical advice and several anonymous reviewers for their suggestions.

This study examined the etiology and course of anxiety symptoms from infancy through adolescence in a longitudinal high-risk community sample. One hundred fifty-five subjects were assessed using a variety of observational, projective, and objective measures. Results of path analyses revealed the following: (a) anxiety symptoms showed moderate stability during childhood and adolescence; (b) heightened neonatal biobehavioral reactivity and poor regulation predicted emotion regulation difficulties in preschool, which predicted anxiety symptoms in childhood; (c) developmental incompetence in childhood predicted anxiety symptoms in preadolescence, and anxiety symptoms in preadolescence predicted incompetence in adolescence; (d) insecure attachment relationships in infancy predicted negative peer relationship representations in preadolescence, and these representations predicted anxiety symptoms in adolescence; (e) compared to males, females showed similar rates of anxiety symptoms in childhood but greater and more stable rates in adolescence; however, males and females showed similar patterns of association between risk factors and anxiety symptoms across childhood and adolescence; and (f) the model tested was specific in predicting anxiety symptoms and not psychopathology in general. The results support a developmental model of the etiology and maintenance of anxiety symptoms in childhood and highlight factors to consider in efforts to prevent and treat childhood anxiety.This article is based on a doctoral dissertation completed by the first author. The research was supported by a Philanthropic Educational Organization Scholarship to the first author and by funds provided by grants to the second author from the Maternal and Child Health Service (MC-R-270416); the William T. Grant Foundation, New York; and the National Institute of Mental Health (MH-40864). This study is currently supported by the National Institute of Mental Health (MH-40864-18). The authors thank Manfred van Dulmen for the invaluable statistical guidance he provided in the preparation of this manuscript and the families and teachers whose generation donation of time made this project possible.

Abnormalities in attention have long been viewed as one of the fundamental underlying cognitive deficits in schizophrenia, likely contributing both to formation of some types of symptoms and particularly to the substantial work and social impairments that often accompany schizophrenia. Yet, the precise nature of the attentional deficits in schizophrenia remains poorly understood. Translating advances in cognitive psychology to clinical research brings paradigms with greater analytic power to the study of attention in schizophrenia. In particular, these paradigms should shed light on whether the attentional dysfunction in schizophrenia is best conceptualized as arising from limitations in amount or allocation of processing capacity or from more specific structural bottlenecks that do not allow certain processes to be carried out in two tasks simultaneously. Certain types of dual-task paradigms are particularly well suited to make distinctive predictions, particularly those involving a psychological refractory period paradigm. The background and design of a series of ongoing studies of prodromal, first-episode, and chronic schizophrenia patients are described that are addressing the developmental course of attentional dysfunction in this disorder. These refined paradigms should substantially increase our understanding of the specific forms of attentional impairment characterizing schizophrenia and their connections to symptom development and functional outcome.

This longitudinal study examined antecedents of substance use behavior among 176 (53% male) adolescents. Adolescents were classified as (a) abstainers (n = 19), (b) experimenters (n = 65), (c) at-risk youth (n = 63), and (d) abusers (n = 29) based on their reported substance use behavior at age 17.5. Parental behavior, peer competence, and problem behavior, measured from early childhood through age 16, were examined as predictors of substance use patterns. Multinomial logistic regression models revealed that early maternal hostility, externalizing behavior problems in first grade and at age 16, internalizing behavior in first grade and at age 16, and parental monitoring at age 16 significantly differentiated substance use groups. The study provides evidence that experiences occurring early in development, in addition to those that occur later in development, can play a pivotal role in setting the stage for late adolescent substance use behavior.Preparation of this work and the research described herein were supported by a grant from the National Institute of Mental Health (R01MH40864-18). We acknowledge the participants and their families for their continued participation in this research. Special thanks to Judy Cook, W. Andrew Collins, and the numerous graduate and undergraduates who made this project possible.

Psychosocial stress plays an important role at multiple junctures in the onset and course of bipolar disorder. Childhood adversity may be a risk factor for vulnerability to early onset illness, and an array of stressors may be relevant not only to the onset, recurrence, and progression of affective episodes, but the highly prevalent substance abuse comorbidities as well. A substantial group of controlled studies indicate that various cognitive behavioral psychotherapies and psychoeducational approaches may yield better outcomes in bipolar disorder than treatment as usual. Yet these approaches do not appear to be frequently or systematically employed in clinical practice, and this may contribute to the considerable residual morbidity and mortality associated with conventional treatment. Possible practical approaches to reducing this deficit (in an illness that is already underdiagnosed and undertreated even with routine medications) are offered. Without the mobilization of new clinical and public health approaches to earlier and more effective treatment and supportive interventions, bipolar illness will continue to have grave implications for many patients' long-term well being.This article was based on work in the Intramural Program of the NIMH and work in the former Stanley Foundation Bipolar Network. The principal investigators of the Network included L. Altshuler, M. Frye, T. Suppes, S. McElroy, P. Keck, Jr., W. Nolen, R. Kupka, J. Walden, and H. Grunze. We also acknowledge the special contributions of D. Luckenbaugh and S. Perez in data analysis and C. Gavin and H. Brightman in manuscript preparation.

A study was conducted to determine predictors of high risk/delinquent behavior and psychoemotional maladjustment in 1,478 sixth and eighth graders who took part in a survey of high-risk and adaptive behaviors. The first goal was to determine the extent to which two distinct dimensions of alienation, normlessness, and isolation/self-estrangement mediated the emergence of maladjustment in youth exposed to community violence. The second goal was to distinguish between violence witnessing and violence victimization, and determine whether these subtypes of violence exposure may differentially affect the proposed mediational factors. The results indicated that normlessness partially mediated the relationship between violence exposure and high-risk/delinquent behavior and between violence exposure and psychoemotional maladjustment. Isolation/self-estrangement partially mediated the relation between violence exposure and psychoemotional maladjustment. Although witnessing of, and victimization by, violence were both significant predictors of normlessness, only violent victimization was significantly linked to isolation/self-estrangement. These results elucidate the mechanisms by which community violence exposure may exert negative influences on youth and suggest that there are distinct patterns of risk associated with different forms of exposure.This research was facilitated by the support of the William T. Grant Foundation and the Harris Program on Social Policy. The authors gratefully acknowledge the New Haven Public Schools, especially Superintendent Dr. Reginald Mayo and Assistant Superintendent Dr. Verdell Roberts. The authors thank Drs. Alan Kazdin, Joseph Mahoney, and Edward Zigler for their helpful feedback on earlier versions of this manuscript.

Schizophrenia has long been approached from a translational perspective; however, new findings from the past decade have radically affected the dominant accounts of this illness. It is now possible to derive a consistent account of one contributing cause of schizophrenia across multiple levels of analysis, from genes to receptors, functional neuroanatomy, cognition, and symptoms. To this end, we summarize the data attributing the disorganization symptoms of schizophrenia to a failure of executive, prefrontal cortical processes. We describe the hypothesis that this failure reflects an impairment in N-methyl-D-aspartate (NMDA) glutamatergic neurotransmission, that is likely to involve both the dysregulated function of NMDA synapses, as well as the physical loss of NMDA synapses, particularly in prefrontal cortex. Dysregulation in NMDA synaptic function can be in turn attributed to polymorphisms in a variety of genes (regulator of G-protein signaling 4, dystrobrevin binding protein 1, neuregulin-1, d-amino acid oxidase activator, and others) that have been linked to schizophrenia and are likely to impact NMDA-mediated synaptic neuroplasticity. Although the science of schizophrenia is not yet at a point where any domain or set of findings provides strong constraints across other levels of analysis, the further development of evidence for this chain of causation can provide increasingly strong tests of the NMDA synapse deficit theory.This work was supported by Grant MH069675 from the National Institute of Health. The authors thank Scott Sponheim and Irving Gottesman for their perspectives and insights on various aspects of the manuscript.

Chronic illnesses often involve repeated hospitalization and invasive treatment procedures that can have a traumatic impact on child development. To explore possible consequences of treatment procedures, three groups of patients with congenital anomalies were examined longitudinally. At first admission, adolescents (ages 10–20, mean 15) with anorectal anomalies (n = 14), adolescents with Hirschsprung disease (n = 14), and hospitalized controls (n = 14) were assessed for treatment procedures, somatic function, mental health, and dissociative experiences. The assessment included the Adolescent Dissociative Experiences Scale (A-DES). At 10-year follow-up, the patients completed the Dissociative Experiences Scale (DES) and the Somatoform Dissociative Questionnaire (SDQ-20). Anal dilatation, an invasive medical treatment procedure performed daily by the parents the first 4 years, was correlated with the frequency and severity of persisting dissociative symptomatology. The procedure was the only significant predictor of A-DES and SDQ-20 scores, and one of two significant predictors of DES scores. This “experiment of nature” permitted a specific and unique opportunity to examine the impact of early traumatic exposure on child development in the absence of parental malevolence, and on later dissociative outcome in adolescence and adulthood. The findings might be valuable theoretically to our understanding of the development of psychopathology, and may lend itself for comparison with data on sexually abused children.

Advances in molecular biology, neuroimaging, genetic epidemiology, and developmental psychopathology have provided a unique opportunity to explore the interplay of genes, brain, and behavior within a translational research framework. Herein, we begin by outlining an experimental strategy by which genetic effects on brain function can be explored using neuroimaging, namely, imaging genetics. We next describe some major findings in imaging genetics to highlight the effectiveness of this strategy for delineating biological pathways and mechanisms by which individual differences in brain function emerge and potentially bias behavior and risk for psychiatric illness. We then discuss the importance of applying imaging genetics to the study of psychopathology within a developmental framework. By beginning to move toward a systems-level approach to understanding pathways to behavioral outcomes as they are expressed across development, it is anticipated that we will move closer to understanding the complexities of the specific mechanisms involved in the etiology of psychiatric disease. Despite the numerous challenges that lie ahead, we believe that developmental imaging genetics has potential to yield highly informative results that will ultimately translate into public health benefits. We attempt to set out guidelines and provide exemplars that may help in designing fruitful translational research applications that incorporate a developmental imaging genetics strategy.This research was supported in part by funding from the United Kingdom National Programme on Forensic Mental Health Research and Development (to E.V.), the Medical Research Council Grant G0401170 (to E.V.), the National Institute of Mental Health Grants K01-MH001957 (to D.E.W.) and K01-MH072837 (to A.R.H.), as well as an NARSAD Young Investigator Award (to A.R.H.).

In a previous paper, the authors found that impairment on the Wisconsin Card Sorting Test (WCST) in adolescence was predictive of bipolar disorder in young adulthood among offspring of mothers with bipolar illness. In the present study, the authors explore the contribution of maternal characteristics, beyond maternal mood disorder, to the prediction of offspring dysfunction on the WCST. Results showed that maternal bipolar disorder and maternal negativity were both predictive of impaired performance on the WCST during adolescence. The contribution of maternal negativity to offspring WCST impairment was not better explained by maternal personality disorder, mother's functional impairment, family loading for bipolar disorder, or offspring disruptive behavioral disturbance. Findings did not support a moderator model. However, support was found for a mediation model in which maternal negativity contributed to risk for offspring bipolar disorder through its negative association with apparent frontal lobe functioning, as measured by the WCST. Findings are discussed from the perspective of a vulnerability–stress model. In addition, the authors consider the possibility that maternal negativity and offspring impairment on the WCST may be reflective of a common heritable trait.The findings presented in this paper come from the doctoral dissertation of the first author, which was funded by an NIMH Intramural Research Training Award. The authors are enormously grateful to Anne Mayfield, without whom this project would not have been possible. We are deeply indebted to Ann S. Masten, W. Andrew Collins, L. Alan Sroufe, Monica Luciana, and Carrie Borchardt, who provided support and guidance throughout all stages of this project. We are also thankful to Robert Asarnow for his advice and encouragement, and to Roger E. Meyer and Daniel N. Klein for their comments on earlier drafts of this paper. In addition, we acknowledge the contributions of Gail Inoff-Germain, who administered diagnostic interviews and neuropsychological measures at adolescent follow-up; Rula B. Garside, who undertook the painstaking job of establishing interrater reliability; Erika Sundstrom, who devoted many hours to data organization and quality assurance; and Sara Avery Torvik and Patricia Kasdan, whose combined gifts of organization and warmth created a comfortable atmosphere for study participants. Finally, we thank the extraordinary research participants of the NIMH Childrearing Study, who have shown enormous bravery and dedication by sharing with us 23 years of their lives.

Bipolar affective disorder is a recurrent, disabling, and potentially lethal illness that typically begins early in life. Although the disorder is defined by the manic and hypomanic episodes, for most people the depression episodes are the more virulent aspect of the illness. Specifically, the depressive episodes are more numerous, last longer, and are more difficult to treat than the manias, and depression is the principal cause of the illness's increased mortality due to suicide. For people with early-onset depression, predictors of subsequent bipolarity include a family history, psychotic features, and reverse neurovegetative features. Initial episodes of depression are commonly misdiagnosed, which often delays initiation of appropriate therapy and increases the likelihood of treatment with antidepressants alone. Unfortunately, the correct diagnosis is often not made until there has been a treatment–emergent affective switch. There are no treatments specifically approved for bipolar disorder in youth and, among antidepressants, only fluoxetine has received approved. When bipolarity is suspected, treatment with mood stabilizers, both conventional (i.e., lithium, valproate, and carbamazapine) and more recently classified (lamotrigine) and atypical antipsychotics should be prioritized. When antidepressants are indicated in combination with mood stabilizers, first choice options include bupropion and the selective serotonin reuptake inhibitors. Studies of adults indicate that several forms of focused psychotherapy may improve longer term outcomes.

This study evaluated Mind Reading, an interactive systematic guide to emotions, for its effectiveness in teaching adults with Asperger syndrome (AS) and high-functioning autism (HFA) to recognize complex emotions in faces and voices. Experiment 1 tested a group of adults diagnosed with AS/HFA (n = 19) who used the software at home for 10–15 weeks. Participants were tested on recognition of faces and voices at three different levels of generalization. A matched control group of adults with AS/HFA (n = 22) were assessed without any intervention. In addition, a third group of general population controls (n = 24) was tested. Experiment 2 repeated the design of Experiment 1 with a group of adults with AS/HFA who used the software at home and met in a group with a tutor on a weekly basis. They were matched to a control group of adults with AS/HFA attending social skills training and to a general population control group (n = 13 for all three groups). In both experiments the intervention group improved significantly more than the control group on close, but not distant, generalization tasks. Verbal IQ had significant effects in Experiment 2. Using Mind Reading for a relatively short period of time allows users to learn to recognize a variety of complex emotions and mental states. However, additional methods are required to enhance generalization.The first author was supported by the National Alliance for Autism Research, the Corob Charitable Trust, the Cambridge Overseas Trust and B'nai B'rith Leo Baeck scholarships. The second author was supported by the Shirley Foundation, the Medical Research Council, and the Three Guineas Trust. We are grateful to the following for helping with this study: our participants, Red Green and Blue Ltd, Jessica Kingsley Ltd, Pamela Yates for arranging and running the social skills groups, Andrea Macleod and Rob Whiskens (Autism West Midlands), Jill Howard (Autism London), Lynne Moxon (European Services for People with Autism), and Harriet Fisher and James Graham (The Interact Centre). Many thanks to Jacqueline Hill, Chris Ashwin, Sally Wheelwright, Matthew Belmonte, Yael Golan, Sarah Johnson, Emma Chapman, and Ilaria Minio Paluello. A version of this work was presented at the International Meeting For Autism Research (IMFAR), May 2004.

This 11-year longitudinal study models the trajectories of depressive symptoms among approximately 550 females and males raised in divorced and nondivorced families in the rural Midwest. Using multilevel analyses, we demonstrate that, first, depressive symptoms changed according to a curvilinear pattern, especially for females; they increased during early to midadolescence and then declined in late adolescence to young adulthood. Second, compared with males, females experienced a greater number of depressive symptoms in adolescence and early adulthood. Third, children who experienced parental divorce by age 15 manifested a sharper increase in depressive symptoms compared to those from nondivorced families. Fourth, stressful life events children experienced shortly after parental divorce mediated the effect of parental divorce on depressive symptoms. Fifth and finally, time-varying stressful life events, particularly those related to relationship and personal loss, were significantly associated with the trajectories of depressive symptoms.During the past several years, support for this research has come from multiple sources including the National Institute of Mental Health (MH00567, MH19734, MH43270, MH48165, MH51361), the National Institute on Drug Abuse (DA05347), the Bureau of Maternal and Child Health (MCJ-109572), the MacArthur Foundation Research Network on Successful Adolescent Development among Youth in High-Risk Settings, the Iowa Agriculture and Home Economics Experiment Station (Project No. 3320), and the California Agriculture Experiment Station (CA-D*-HCD-6092-H).

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.

Despite the high prevalence rate, there have been relatively few controlled studies to systematically examine pharmacological treatments for children and adolescents with bipolar disorder. We review the differences in clinical characteristics between youth and adults with bipolar disorder and the extant literature of pharmacological treatments for children and adolescents with bipolar disorder, as well as discuss the effectiveness of pharmacological interventions for treating children and adolescents who are at familial risk for developing bipolar disorder. Although the number of controlled studies of youth with manic and mixed episodes is rapidly growing, there are few studies examining treatments for depression and the prevention of recurrent affective episodes in this population. Although children and adolescents with bipolar disorder commonly present with co-occurring psychiatric disorders, such as attention-deficit/hyperactivity disorder, there are limited data to guide the treatment of these patients. Recently, studies have begun to characterize prodromal manifestations of bipolar disorder and identify early intervention strategies for treating children and adolescents with an elevated risk for developing bipolar disorder.

Mood disorder symptoms and their associated functional impairments are hypothesized to come about as the result of the conjoint, interactive influences of genetic, biological, and psychological vulnerabilities, family distress, and life stress at different points of development. We discuss a developmental psychopathology model that delineates pathways to high family conflict and mood exacerbation among early-onset bipolar patients. New data from a treatment development study indicate that adolescent bipolar patients in high expressed emotion families have more symptomatic courses of illness over 2 years than adolescents in low expressed emotion families. Chronic and episodic stressors are also correlated with lack of mood improvement while adolescents are in treatment. Family-focused treatment (FFT) given in conjunction with pharmacotherapy appears to ameliorate the course of bipolar disorder in adults. This treatment has recently been modified to address the developmental presentation of bipolar disorder among adolescents. We present data from an open trial of FFT and pharmacotherapy (N = 20) indicating that bipolar adolescents stabilize in mania, depression, and parent-rated problem behaviors over 2 years. Future research should focus on clarifying the developmental pathways to early-onset bipolar disorder and the role of protective factors and preventative psychosocial interventions in delaying the first onset of the disorder.This research was supported by National Institute of Mental Health Grants MH43931, MH62555, and MH073871; a Distinguished Investigator Award from the National Alliance for Research on Schizophrenia and Depression; and a grant from the Robert Sutherland Foundation.

Data gathered over the course of a 25-year longitudinal study of 1,055 young people was used to examine gender differences in the onset of early parenthood and the developmental processes that place males and females at risk of becoming a young parent. Results revealed clear gender differences in the timing of early parenthood, with females being twice as likely as males to become a parent between the ages of 16 and 25 years. In contrast, the risk factors and life course processes that placed males and females at risk of an early transition to parenthood were very similar. Two exceptions were a gender-specific effect for maternal age and exposure to parental change, suggesting that having been raised by a younger mother and having experienced parental changes in your family of origin increased risks of early parenthood for females but not males. These findings contribute to our understanding of the effects of gender on life course development.This research was funded by grants from the Health Research Council of New Zealand, the National Child Health Research Foundation, the Canterbury Medical Research Foundation and the New Zealand Lottery Grants Board.

The role of biobehavioral sciences is critically evaluated within the model for translational research proposed in the NIH Roadmap. Concern is expressed regarding the lack of specification and representation of intervening disciplines along the translational chain from assessment to treatment to outcome. The implications of this model on the future of developmental psychopathology are discussed. A new model is proposed that emphasizes the role of biobehavioral sciences in translational research focusing on psychiatric disorders.The preparation of this manuscript was supported in part by a grant from the National Institutes of Health (MH 067446).

Interpersonal and social rhythm therapy (IPSRT) is a manual-based adjunctive psychotherapy specific to the treatment of bipolar disorder. This paper reviews the theoretical rationale and empirical evidence for the efficacy of IPSRT in combination with pharmacotherapy for adults with bipolar I disorder. We then provide an overview of the developmental modifications being made to IPSRT to increase its relevance to adolescents with bipolar disorder.To protect confidentiality, case examples are composites of several different adolescents receiving IPSRT. Patients' real names were not used in this report. The authors are grateful to Elizabeth McCauley and Carolyn McCarty for their thoughtful comments on an earlier draft of this article. We also thank Laura Mufson for her sage advice regarding the developmental adaptations being made to IPSRT to be more relevant to adolescents with bipolar disorder. This work was supported by National Institute of Mental Health (Bethesda, MD) Grants MH70570 (S.H.) and MH29618 (E.F.) and General Clinical Research Center Grant M01-RR00037.