Bipolar disorder (BD) is a chronic, recurrent disorder carrying high morbidity and mortality, leading to health costs of at least $45 billion per year (Kleinman et al., 2003). It is the sixth leading cause of disability among all illnesses (Murray & Lopez, 1996). Between 15 and 28% of bipolar adults experience illness onset before the age of 13, and between 50 and 66% of them experience it before the age of 19 (Leverich et al., 2002, 2003; Perlis et al., 2004). The exact prevalence in children is unknown, but an estimated 420,000–2,072,000 US children have the illness (Post & Kowatch, 2006). Persons with onset of BD in childhood or adolescence have a more severe, adverse, and continuously cycling course of illness than adults, often with a preponderance of mixed episodes, psychosis, suicidal ideation or behaviors, and multiple comorbidities (Geller et al., 2002). Without early intervention, early-onset BD patients can be derailed, sometimes irrevocably, in social, neurobiological, cognitive, and emotional development (Miklowitz et al., 2004).Our work on this Special Issue and editorial was partially supported by grants from the National Institute of Drug Abuse, the National Institute of Mental Health, and the Spunk Fund, Inc.

This review addresses the phenomenology of mania/bipolar disorder from a developmental psychopathology perspective and uses cases with longitudinal information to illustrate major points. Beginning with a summary of the phenomenology of bipolar illness as it occurs in adults, the authors identify diagnostic complexities unique to children and adolescents. These include the challenges of characterizing elation and grandiosity; differentiating mania from comorbid symptoms, rages, sequelae of maltreatment, and typical developmental phenomena; and the unique manifestations of psychosis. We conclude with the observation that a significant difference between early and later onset bipolar disorder is that, in the former, there appears to be a global delay or arrest in the development of appropriate affect regulation; whereas in adult-onset bipolar illness, emotion dysregulation generally presents as an intermittent phenomenon. At this juncture, the study of childhood bipolar illness would benefit from a developmental psychopathology perspective to move beyond the level of cross-sectional symptom description to begin to study individuals over time, focusing on developmental, environmental, genetic, and neurobiological influences on manifest behavior.This review was supported in part by funding from NIMH Grant 44801 and grants from Janssen Pharmaceutica and Abbott Laboratories.

The clinical characteristics and adaptive functioning of preschoolers who met DSM-IV criteria for bipolar disorder versus psychiatric and healthy comparison groups were investigated. A community-based sample of 303 preschoolers (3–6 years of age) and their caregivers was ascertained. Diagnostic classification based on parent report of mania symptoms was made using an age-appropriate psychiatric interview. Results indicated that 26 preschoolers met DSM-IV criteria for bipolar disorder who could be identified based the presence of 13 core age-adjusted mania items. These children could be clearly differentiated from children in two psychiatric groups (DSM-IV disruptive disorders, and major depressive disorder) and a “healthy” comparison group based on a specific symptom constellation. Findings indicated that preschoolers in the bipolar group were significantly more (p < .05) impaired than the two psychiatric and healthy groups based on independent measures. Further, even after controlling for comorbid attention-deficit/hyperactivity disorder (81% comorbidity rate), the bipolar group remained significantly (p < .05) more impaired in multiple domains compared to preschoolers with DSM-IV disruptive disorders and healthy controls. Findings suggested that children as young as 3 years can manifest DSM-IV bipolar disorder when age adjusted symptom descriptions are employed, and that these children can be distinguished from healthy and disruptive disordered preschoolers. Recommendations for future research in this area that integrates developmental and mental health models are made.We gratefully acknowledge Edward Spitznagel for his statistical consultation. We are also grateful to the The Early Emotional Development Program staff, our preschool participants and their parents, and community recruiting sites whose participation and cooperation made this research possible. Funding for the study of preschool depression was provided by NIMH Grant NIMH R01 MH64769-01 (to J.L.).

The goal of this paper is to review assessment research of bipolar disorder in children and adolescents. The review addresses numerous themes: the benefits and costs of involving clinical judgment in the diagnostic process, particularly with regard to diagnosis and mood severity ratings; the validity of parent, teacher, and youth self-report of manic symptoms; how much cross-situational consistency is typically shown in mood and behavior; the extent to which a parent's mental health status influences their report of child behavior; how different measures compare in terms of detecting bipolar disorder, the challenges in comparing the performance of measures across research groups, and the leading candidates for research or clinical use; evidence-based strategies for interpreting measures as diagnostic aids; how test performance changes when a test is used in a new setting and what implications this has for research samples as well as clinical practice; the role of family history of mood disorder within an assessment framework; and the implications of assessment research for the understanding of phenomenology of bipolar disorder from a developmental framework.We thank the families who participated in this program of research. This work was supported in part by NIMH R01 MH066647, as well as a Center Grant from the Stanley Medical Research Institute.

The longitudinal course of children and adolescents with bipolar disorder (BP) is manifested by frequent changes in symptom polarity with a fluctuating course showing a dimensional continuum of bipolar symptom severity from subsyndromal to mood syndromes meeting full Diagnostic and Statistical Manual of Mental Disorders criteria. These rapid fluctuations in mood appear to be more accentuated than in adults with BP, and combined with the high rate of comorbid disorders and the child's cognitive and emotional developmental stage, may explain the difficulties encountered diagnosing and treating BP youth. Children and adolescents with early-onset, low socioeconomic status, subsyndromal mood symptoms, long duration of illness, rapid mood fluctuation, mixed presentations, psychosis, comorbid disorders, and family psychopathology appear to have worse longitudinal outcome. BP in children and adolescents is associated with high rates of hospitalizations, psychosis, suicidal behaviors, substance abuse, family and legal problems, as well as poor psychosocial functioning. These factors, in addition to the enduring and rapid changeability of symptoms of this illness from very early in life, and at crucial stages in their lives, deprive BP children of the opportunity for normal psychosocial development. Thus, early recognition and treatment of BP in children and adolescents is of utmost importance.This work was supported in part by grant MH59929 from the National Institute of Mental Health. The authors thank Carol Kostek for her assistance with manuscript preparation and Editha Nottelmann, PhD, and Regina James, MD, for their continued support.

Rate, risk, and predictors of switching from attention-deficit/hyperactivity disorder (ADHD) to a prepubertal and early adolescent bipolar I disorder phenotype (PEA-BP-I) were examined in a blindly rated, controlled, prospective 6-year follow-up that included assessments at 2-year intervals. Subjects were outpatients obtained by consecutive new case ascertainment. There were 81 subjects who were 9.7 ± 2.0 years. Subjects had DSM-IV ADHD (hyperactive or combined subtypes); a Children's Global Assessment Scale (CGAS) score of ≤60, consistent with moderate–severe impairment; and no BP or major depressive disorder (MDD) diagnoses. PEA-BP-I was defined as DSM-IV BP I (manic or mixed phase), with cardinal symptoms (elation and/or grandiosity), to avoid diagnosing mania by symptoms that overlapped with those of ADHD, and by a CGAS score of ≤60. Morbid risk of switching to PEA-BP-I was 28.5%. Significant predictors of switching in a multivariate Cox model were more severe baseline CGAS, paternal recurrent MDD, and less stimulant use. BP I in first-degree relatives, antidepressants, psychosocial measures, and life events were not predictive.This work was supported by National Institute of Mental Health Grants R01 MH-53063 and R01 MH-57451 (to B.G.).

Why is adolescence an “age of risk” for onset of bipolar spectrum disorders? We discuss three clinical phenomena of bipolar disorder associated with adolescence (adolescent age of onset, gender differences, and specific symptom presentation) that provide the point of departure for this article. We present the cognitive vulnerability–transactional stress model of unipolar depression, evidence for this model, and its extension to bipolar spectrum disorders. Next, we review evidence that life events, cognitive vulnerability, the cognitive vulnerability–stress combination, and certain developmental experiences (poor parenting and maltreatment) featured in the cognitive vulnerability–stress model play a role in the onset and course of bipolar disorders. We then discuss how an application of the cognitive vulnerability–stress model can explain the adolescent age of onset, gender differences, and adolescent phenomenology of bipolar disorder. Finally, we further elaborate the cognitive vulnerability–stress model by embedding it in the contexts of normative adolescent cognitive (executive functioning) and brain development, normative adolescent development of the stress–emotion system, and genetic vulnerability. We suggest that increased brain maturation and accompanying increases in executive functioning along with augmented neural and behavioral stress–sensitivity during adolescence combine with the cognitive vulnerability–stress model to explain the high-risk period for onset of bipolar disorder, gender differences, and unique features of symptom presentation during adolescence.Preparation of this article was supported by National Institute of Mental Health Grants MH 52617 (to L.B.A.) and 52662 (to L.Y.A.).

Much controversy has surrounded the diagnosis of bipolar disorder (BD) in children and adolescents. However, recent work from an affective neuroscience perspective has advanced what is known about the boundaries of emotion regulation in BD compared to typically developing youth. In this article, we first briefly review the clinical issues that have contributed to this diagnostic controversy. Second, we discuss our phenotyping system, which can be used to guide neurobiological research designed to address these controversial issues. Third, we review what is known about the fundamentals of emotion regulation in human and nonhuman primate models. Fourth, we present recent data demonstrating how children and adolescents with BD differ from those without psychopathology on measures of emotion regulation. Taken as a whole, this work implicates a neural circuit encompassing the prefrontal cortex, amygdala, and striatum in the pathophysiology of pediatric BD.Both authors are affiliated with the Mood and Anxiety Disorders Program of the National Institute of Mental Health's Division of Intramural Research Programs (NIMH DIRP), which funded the work in its entirety. Dr. Dickstein is currently supported by a career development award (K22-MH 74945).

There is a great need for discovery of biological markers that could be used diagnostically for pediatric onset disorders, particularly those with potentially confusing phenomenology such as pediatric-onset bipolar disorder (BD). Obtaining these markers would help overcome current subjective diagnostic techniques of relying on parent and child interview and symptomatic history. Brain imaging may be the most logical choice for a diagnostic tool, and certain neurobiological abnormalities have already been found in pediatric BD. However, much work remains to be done before neuroimaging can be used reliably to diagnose this disorder, and because of the nature of BD and the limitations of imaging technology and technique, neuroimaging will likely at most be only a diagnostic aide in the near future. In this paper we discuss the characteristics of pediatric BD that complicate the use of biological markers as diagnostic tools, how neuroimaging techniques have been used to study pediatric BD so far, and the limitations and potential of such techniques for future diagnostic use.This work was supported in part by NIH Grant MH64460-01 (to K.C.).

The aim of this paper is to highlight the importance of the sleep–wake cycle in children and adolescents with bipolar disorder. After presenting an overview of the measurement and function of human sleep, we describe changes in sleep and circadian functioning across the life cycle. We then review evidence that, in adults, sleep and/or circadian rhythms are of considerable influence in the multifactorial causal chain implicated in relapse in bipolar disorder, discussing relevant mechanisms. The latter include abnormalities in the amount and timing of sleep, the role of social zeitgebers, and the importance of sleep in regulating emotional responses and mood. We next present preliminary data indicating considerable sleep disturbance among children and adolescents with bipolar disorder. Given the considerable sleep disturbance evident among children and adolescents with bipolar disorder along with a key role for sleep in emotion regulation and learning, we conclude that sleep among children and adolescents with bipolar disorder is a critical domain for future research. An agenda for future research is presented that includes descriptive studies, investigations of causality, and treatment development research.

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.

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.

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.

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.

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.

Bipolar disorder (BPD) has received increasing attention from public and professional sources. Although pharmacologic treatments are considered the sine qua non in the treatment of youth with BPD, psychosocial interventions are critical to assist the child and family cope with symptoms that carry with them significant morbidity and mortality. Treatments developed to date are few in number; all are psychoeducationally based, using cognitive–behavioral and family systems interventions within a biopsychosocial framework. This paper reviews possible mediators of outcome, including caregiver concordance, children's social skills, hopelessness, and family stress. The author has developed two family-based psychoeducational interventions for the treatment of youth with BPD: multifamily psychoeducation groups (MFPG) and individual family psychoeducation (IFP). These treatments are both described and the results from a previously published randomized clinical trial (RCT) of MFPG are summarized. Then, new findings from an RCT of IFP are presented, along with preliminary pilot data from an expanded version of IFP. The paper concludes with recommendations for future research.This paper was supported by grants to the author from the National Institute of Mental Health (R01-MH61512) and the Ohio Department of Mental Health (ODMH-743074 and 734030).

In addition to members of the Editorial Board, we sought reviews from a number of other scholars. We wish to acknowledge our appreciation to all those who returned reviews during 2006.