Bipolar Disorder: Birmaher B

Kowatch RA, Fristad M, Birmaher B, Wagner KD, Findling RL, Hellander M, Anonymous00051. · Department of Psychiatry, Cincinnati Children's Hospital Medical, OH 45267-0559, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #15725966 No free full text.

Abstract: Clinicians who treat children and adolescents with bipolar disorder desperately need current treatment guidelines. These guidelines were developed by expert consensus and a review of the extant literature about the diagnosis and treatment of pediatric bipolar disorders. The four sections of these guidelines include diagnosis, comorbidity, acute treatment, and maintenance treatment. These guidelines are not intended to serve as an absolute standard of medical or psychological care but rather to serve as clinically useful guidelines for evaluation and treatment that can be used in the care of children and adolescents with bipolar disorder. These guidelines are subject to change as our evidence base increases and practice patterns evolve.

Birmaher B. · No affiliation provided · Am J Psychiatry. · Pubmed #17403961 links to  free full text

This publication has no abstract.

Youngstrom EA, Birmaher B, Findling RL. · Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3270, USA. · Bipolar Disord. · Pubmed #18199237 No free full text.

Abstract: OBJECTIVE: To find, review, and critically evaluate evidence pertaining to the phenomenology of pediatric bipolar disorder and its validity as a diagnosis. METHODS: The present qualitative review summarizes and synthesizes available evidence about the phenomenology of bipolar disorder (BD) in youths, including description of the diagnostic sensitivity and specificity of symptoms, clarification about rates of cycling and mixed states, and discussion about chronic versus episodic presentations of mood dysregulation. The validity of the diagnosis of BD in youths is also evaluated based on traditional criteria including associated demographic characteristics, family environmental features, genetic bases, longitudinal studies of youths at risk of developing BD as well as youths already manifesting symptoms on the bipolar spectrum, treatment studies and pharmacologic dissection, neurobiological findings (including morphological and functional data), and other related laboratory findings. Additional sections review impairment and quality of life, personality and temperamental correlates, the clinical utility of a bipolar diagnosis in youths, and the dimensional versus categorical distinction as it applies to mood disorder in youths. RESULTS: A schema for diagnosis of BD in youths is developed, including a review of different operational definitions of 'bipolar not otherwise specified.' Principal areas of disagreement appear to include the relative role of elated versus irritable mood in assessment, and also the limits of the extent of the bipolar spectrum--when do definitions become so broad that they are no longer describing 'bipolar' cases? CONCLUSIONS: In spite of these areas of disagreement, considerable evidence has amassed supporting the validity of the bipolar diagnosis in children and adolescents.

Birmaher B, Axelson D. · Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, PA 15213, USA. · Dev Psychopathol. · Pubmed #17064427 No free full text.

Abstract: 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.

Strober M, Birmaher B, Ryan N, Axelson D, Valeri S, Leonard H, Iyengar S, Gill MK, Hunt J, Keller M. · Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90024-1759, USA. · Bipolar Disord. · Pubmed #16879132 links to  free full text

Abstract: AIM AND METHODS: Findings from recent long-term, prospective longitudinal studies of the course, outcome and naturalistic treatment of adults with bipolar illness are highlighted as background for long-term developmental study of pediatric bipolar illness. RESULTS: Accumulating knowledge of bipolar illness in adults underscores a high risk for multiple recurrences through the lifespan, significant medical morbidity, high rates of self-harm, economic and social burden and frequent treatment resistance with residual symptoms between major episodes. At present, there is no empirical foundation to support any assumption about the long-term course or outcome of bipolar illness when it arises in childhood or adolescence, or the effects of conventional pharmacotherapies in altering its course and limiting potentially adverse outcomes. The proposed research articulates specific descriptive aims that draw on adult findings and outlines core methodological requirements for such an endeavor. CONCLUSIONS: Innovations in the description and quantitative analysis of prospective longitudinal clinical data must now be extended to large, systematically ascertained pediatric cohorts recruited through multicenter studies if there is to be a meaningful scientific advance in our knowledge of the enduring effects of bipolar illness and the potential value of contemporary approaches to its management.

Zalsman G, Birmaher B, Brent DA. · Neuroscience Division, Columbia University, USA. · Harefuah. · Pubmed #16642632 No free full text.

Abstract: Early onset depression is a widely prevalent, recurrent and familial disorder with a tendency to continue throughout adulthood. It is often accompanied by other comorbidities such as substance abuse, bipolar disorder, suicidal behavior and significant impairment in the child's psychosocial development. The risk factors include genetic, psychological and environmental factors and gene-environment interaction. The evidence-based therapies include cognitive, inter-personal and pharmacological interventions. Recently, the FDA published a warning concerning the use of these pharmacological agents in the pediatric age group. Further research is needed to assess the efficacy and safety of these interventions and to better understand the etiological factors.

Pavuluri MN, Birmaher B, Naylor MW. · Pediatric Mood Disorders Clinic and Bipolar Research Program, Department of Psychiatry, University of Illinois at Chicago, 60612-7327, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #16113615 No free full text.

Abstract: OBJECTIVE: To review the literature of the past decade covering the epidemiology, clinical characteristics, assessment, longitudinal course, biological and psychosocial correlates, and treatment and prevention of pediatric bipolar disorder (BD). METHOD: A computerized search for articles published during the past 10 years was made and selected studies are presented. RESULTS: Pediatric BD is increasingly recognized, and there are several prevailing views on core features of this disorder. The incidence and prevalence of the disorder and the associated comorbidities vary according to study setting and criteria used. This disorder is highly recurrent and accompanied by substantial psychiatric and psychosocial morbidity. Familial studies, including "top down" (offspring of parents with BD) and "bottom up" (relatives of youths with BD) studies indicate that pediatric BD is aggregated in families with adult or later-onset BD and suggest the existence of genetic predisposition. Greater understanding of the risk factors for early onset BD and recognition of the phenomenology of prodromal symptoms offers hope for early identification and prevention. Neuroimaging studies indicate frontotemporal and frontostriatal pathology, but none of these findings seems to be disorder specific. Combination pharmacotherapies appear promising, and the field awaits further short- and long-term randomized, placebo-controlled trials. Preliminary studies of various psychotherapies, including psychoeducation strategies tailored specifically for BD in youths, look encouraging. CONCLUSIONS: Considerable advances have been made in our knowledge of pediatric BD; however, differing viewpoints on the clinical presentation of BD in children are the rule. Phenomenological and longitudinal studies and biological validation using genetic, neurochemical, neurophysiological, and neuroimaging methods may strengthen our understanding of the phenocopy. Randomized, controlled treatment studies for the acute and maintenance treatment of BD disorder are warranted.

Birmaher B, Arbelaez C, Brent D. · Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania, 3811 O'Hara Street, Pittsburgh, PA 15213-3811, USA. · Child Adolesc Psychiatr Clin N Am. · Pubmed #12222086 No free full text.

Abstract: Major depressive disorder (MDD) is a familial recurrent illness that significantly interferes with the child's normal development and is associated with increased risk for suicidal behaviors and psychiatric and psychosocial morbidity. Although most children and adolescents recover from their first depressive episode, 30-70%, in particular those with familial history of MDD, comorbid psychiatric disorders, dysthymia, subsyndromal symptoms of depression, anxiety, negative cognitive style, and exposure to negative life events (e.g., family conflicts and abuse) will experience one or more depressive recurrences during their childhood, adolescence, and adulthood. Depressed youth who present with psychosis, psychomotor retardation, pharmacological induced hypomania/mania, and/or family history of bipolar disorder are at high risk to develop bipolar disorder.

Brent DA, Birmaher B. · Western Psychiatric Institute and Clinic, Division of Child and Adolescent Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, USA. · N Engl J Med. · Pubmed #12200555 No free full text.

This publication has no abstract.

Renaud J, Axelson D, Birmaher B. · Department of Psychiatry, University of Pittsburgh, School of Medicine, Western Psychiatric Institute and Clinic, Pennsylvania 15213, USA. · Drug Saf. · Pubmed #9935277 No free full text.

Abstract: Child and adolescent major depressive disorders are common and recurrent disorders. The prevalence of major depressive disorders is estimated to be approximately 2% in children and 4 to 8% in adolescents. Major depressive disorders in children are frequently accompanied by other psychiatric disorders, poor psychosocial outcome and a high risk of suicide and substance abuse, indicating the need for effective treatment and prevention. The use of antidepressant medications as the first line of treatment for children and adolescents with mild to moderate major depressive disorders has been questioned. However, some subgroups of patients may benefit from initial treatment with antidepressants. These subgroups may include patients who are unwilling or unable to undergo psychotherapy, have not responded to at least 8 to 12 sessions of psychotherapy, have bipolar, atypical or severe depression or have recurrent depression. Currently, the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors are the first medication choice because of their efficacy, benign adverse effect profile, ease of use and low risk of death following an overdose. Further research in continuation and maintenance treatments, treatment of comorbid conditions, subtypes of depression, e.g. bipolar, atypical, seasonal, and combinations of pharmacotherapy and psychotherapy are needed. In addition, studies of the pharmacokinetics, pharmacodynamics and long term adverse effects of antidepressant medications in children and adolescents are warranted.

Goldstein TR, Axelson DA, Birmaher B, Brent DA. · Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #17581446 No free full text.

Abstract: OBJECTIVE: To describe an adapted version of dialectical behavior therapy for adolescents with bipolar disorder. METHOD: The dialectical behavior therapy intervention is delivered over 1 year and consists of two modalities: family skills training (conducted with individual family units) and individual therapy. The acute treatment period (6 months) includes 24 weekly sessions; sessions alternate between the two treatment modalities. Continuation treatment consists of 12 additional sessions tapering in frequency through 1 year. We conducted an open pilot trial of the treatment, designed as an adjunct to pharmacological management, to establish feasibility and acceptability of the treatment for this population. Participants included 10 patients (mean age 15.8 +/- 1.5 years, range 14-18) receiving treatment in an outpatient pediatric bipolar specialty clinic. Symptom severity and functioning were assessed quarterly by an independent evaluator. Consumer satisfaction was also assessed posttreatment. RESULTS: Feasibility and acceptability of the intervention were high, with 9 of 10 patients completing treatment, 90% of scheduled sessions attended, and high treatment satisfaction ratings. Patients exhibited significant improvement from pre- to posttreatment in suicidality, nonsuicidal self-injurious behavior, emotional dysregulation, and depressive symptoms. CONCLUSIONS: Dialectical behavior therapy may offer promise as an approach to the psychosocial treatment of adolescent bipolar disorder.

Miklowitz DJ, George EL, Axelson DA, Kim EY, Birmaher B, Schneck C, Beresford C, Craighead WE, Brent DA. · Department of Psychology, University of Colorado, Boulder, CO 80309-0345, USA. · J Affect Disord. · Pubmed #15571785 No free full text.

Abstract: BACKGROUND: Research has begun to elucidate the optimal pharmacological treatments for pediatric-onset bipolar patients, but few studies have examined the role of psychosocial interventions as adjuncts to pharmacotherapy in maintenance treatment. This article describes an adjunctive family-focused psychoeducational treatment for bipolar adolescents (FFT-A). The adult version of FFT has been shown to be effective in forestalling relapses in two randomized clinical trials involving bipolar adults. METHODS: FFT-A is administered to adolescents who have had an exacerbation of manic, depressed, or mixed symptoms within the last 3 months. It is given in 21 outpatient sessions of psychoeducation, communication enhancement training, and problem solving skills training. We describe modifications to the adult FFT model to address the developmental issues and unique clinical presentations of pediatric-onset patients. RESULTS: An open treatment trial involving 20 bipolar adolescents (11 boys, 9 girls; mean age 14.8+/-1.6) found that the combination of FFT-A and mood stabilizing medications was associated with improvements in depression symptoms, mania symptoms, and behavior problems over 1 year. LIMITATIONS: These early results are based on a small-scale open trial. CONCLUSIONS: Results from an ongoing randomized controlled trial will clarify whether combining FFT-A with pharmacotherapy improves the 2-year course of adolescent bipolar disorder. If the results are positive, then a structured manual-based psychosocial approach will be available for clinicians who treat adolescent bipolar patients in the community.

Axelson DA, Bertocci MA, Lewin DS, Trubnick LS, Birmaher B, Williamson DE, Ryan ND, Dahl RE. · Department of Psychiatry, University of Pittsburgh Medical Center, Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania 15213, USA. · J Child Adolesc Psychopharmacol. · Pubmed #14642013 No free full text.

Abstract: This article describes the theoretical background and methodology of ecological momentary assessment (EMA) and reports results from a pilot study using EMA techniques in 16 children and adolescents with affective disorders and 5 subjects who were healthy and at low risk to develop future affective disorders. Multiple daily assessments of the subjects' mood, thoughts, and behaviors were performed in their natural environments using brief interviews on cellular phone calls by the study staff and by wrist actigraphy. The pilot results demonstrated that the EMA methodology is feasible in this population, as 17 of 21 subjects were able to complete the entire 8-week protocol. The potential usefulness of the EMA methodology is illustrated by specific case reports. Potential applications of the EMA methodology to the study of neurobehavioral systems and the pathophysiology of pediatric affective disorders are discussed.

Kupfer DJ, Axelson DA, Birmaher B, Brown C, Curet DE, Fagiolini A, Frank E, Friedman ES, Grochocinski VJ, Houck PR, Kilbourne AM, Mulsant BH, Pollock BG, Reynolds CF, Stofko MG, Swartz HA, Thase ME, Turkin SR, Whyte EM. · Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, 3811 O'Hara St., Pittsburgh, PA 15213, USA. · Psychiatr Serv. · Pubmed #19564218 No free full text.

Abstract: OBJECTIVE: Adolescents, elderly persons, African Americans, and rural residents with bipolar disorder are less likely than their middle-aged, white, urban counterparts to be diagnosed, receive adequate treatment, remain in treatment once identified, and have positive outcomes. The Bipolar Disorder Center for Pennsylvanians (BDCP) study was designed to address these disparities. This report highlights the methods used to recruit, screen, and enroll a cohort of difficult-to-recruit individuals with bipolar disorder. METHODS: Study sites included three specialty clinics for bipolar disorder in a university setting and a rural behavioral health clinic. Study operations were standardized, and all study personnel were trained in study procedures. Several strategies were used for recruitment. RESULTS: It was possible to introduce the identical assessment and screening protocol in settings regardless of whether they had a history of implementing research protocols. This protocol was also able to be used across the age spectrum, in urban and rural areas, and in a racially diverse cohort of participants. Across the four sites 515 individuals with bipolar disorder were enrolled as a result of these methods (69 African Americans and 446 non-African Americans). Although clinical characteristics at study entry did not differ appreciably between African Americans and non-African Americans, the pathways into treatment differed significantly. CONCLUSIONS: Rigorous recruitment and assessment procedures can be successfully introduced in different settings and with different patient cohorts, thus facilitating access to high-quality treatment for individuals who frequently do not receive appropriate care for bipolar disorder.

Fagiolini A, Frank E, Axelson DA, Birmaher B, Cheng Y, Curet DE, Friedman ES, Gildengers AG, Goldstein T, Grochocinski VJ, Houck PR, Stofko MG, Thase ME, Thompson WK, Turkin SR, Kupfer DJ. · Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, PA 15213, USA. · Bipolar Disord. · Pubmed #19500091 No free full text.

Abstract: INTRODUCTION: We developed models of Specialized Care for Bipolar Disorder (SCBD) and a psychosocial treatment [Enhanced Clinical Intervention (ECI)] that is delivered in combination with SCBD. We investigated whether SCBD and ECI + SCBD are able to improve outcomes and reduce health disparities for young and elderly individuals, African Americans, and rural residents with bipolar disorder. METHOD: Subjects were 463 individuals with bipolar disorder, type I, II, or not otherwise specified, or schizoaffective disorder, bipolar type, randomly assigned to SCBD or ECI + SCBD and followed longitudinally for a period of one to three years at four clinical sites. RESULTS: Both treatment groups significantly improved over time, with no significant differences based on age, race, or place of residence, except for significantly greater improvement among elderly versus adult subjects. Improvement in quality of life was greater in the ECI + SCBD group. Of the 299 participants who were symptomatic at study entry, 213 achieved recovery within 24 months, during which 86 of the 213 subjects developed a new episode. No significant difference was found for race, place of residence, or age between the participants who experienced a recurrence and those who did not. However, the adolescent patients were less likely than the adult and elderly patients to experience a recurrence. CONCLUSION: This study demonstrated the effectiveness of SCBD and the additional benefit of ECI independent of age, race, or place of residence. It also demonstrated that new mood episodes are frequent in individuals with bipolar disorder who achieve recovery and are likely to occur in spite of specialized, guideline-based treatments.

Hunt J, Birmaher B, Leonard H, Strober M, Axelson D, Ryan N, Yang M, Gill M, Dyl J, Esposito-Smythers C, Swenson L, Goldstein B, Goldstein T, Stout R, Keller M. · Warren Alpert Medical School, Brown University, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #19465878 No free full text.

Abstract: OBJECTIVE: To determine whether some children with bipolar disorder (BP) manifest irritability without elation and whether these children differ on sociodemographic, phenotypic, and familial features from those who have elation and no irritability and from those who have both. METHOD: Three hundred sixty-one youths with BP recruited into the three-site Course and Outcome of Bipolar Illness in Youth study were assessed at baseline and for most severe past symptoms using standardized semistructured interviews. Bipolar disorder subtype was identified, and frequency and severity of manic symptoms were quantified. The subjects were required to have episodic mood disturbance to be diagnosed with BP. The sample was then reclassified and compared based on the most severe lifetime manic episode into three subgroups: elated only, irritable only, and both elated and irritable. RESULTS: Irritable-only and elated-only subgroups constituted 10% and 15% of the sample, respectively. Except for the irritable-only subjects being significantly younger than the other two subgroups, there were no other between-group sociodemographic differences. There were no significant between-group differences in the BP subtype, rate of psychiatric comorbidities, severity of illness, duration of illness, and family history of mania in first- or second-degree relatives and other psychiatric disorders in first-degree relatives, with the exception of depression and alcohol abuse occurring more frequently in the irritability-only subgroup. The elated-only group had higher scores on most DSM-IV mania criterion B items. CONCLUSIONS: The results of this study support the DSM-IV A criteria for mania in youths. Irritable-only mania exists, particularly in younger children, but similar to elated-only mania, it occurs infrequently. The fact that the irritable-only subgroup has similar clinical characteristics and family histories of BP, as compared with subgroups with predominant elation, provides support for continuing to consider episodic irritability in the diagnosis of pediatric BP.

Miklowitz DJ, Axelson DA, George EL, Taylor DO, Schneck CD, Sullivan AE, Dickinson LM, Birmaher B. · Department of Psychology, University of Colorado, Boulder, CO 80309, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #19454920 No free full text.

Abstract: OBJECTIVE: Family interventions have been found to be effective in pediatric bipolar disorder (BD). This study examined the moderating effects of parental expressed emotion (EE) on the 2-year symptomatic outcomes of adolescent BD patients assigned to family-focused therapy for adolescents (FFT-A) or a brief psychoeducational treatment (enhanced care [EC]). METHOD: A referred sample of 58 adolescents (mean age 14.5 +/- 1.6 years, range 13-17 years) with BD I, II, or not otherwise specified was randomly allocated after a mood episode to FFT-A or EC, both with protocol pharmacotherapy. Levels of EE (criticism, hostility, or emotional overinvolvement) in parents were assessed through structured interviews. Adolescents and parents in FFT-A underwent 21 sessions in 9 months of psychoeducation, communication training, and problem-solving skills training, whereas adolescents and parents in EC underwent 3 psychoeducation sessions. Independent "blind" evaluators assessed adolescents' depressive and manic symptoms every 3 to 6 months for 2 years. RESULTS: Parents rated high in EE described their families as lower in cohesion and adaptability than parents rated low in EE. Adolescents in high-EE families showed greater reductions in depressive and manic symptoms in FFT-A than in EC. Differential effects of FFT-A were not found among adolescents in low-EE families. The results could not be attributed to differences in medication regimens. CONCLUSIONS: Parental EE moderates the impact of family intervention on the symptomatic trajectory of adolescent BD. Assessing EE before family interventions may help determine which patients are most likely to benefit from treatment.

Birmaher B, Axelson D, Goldstein B, Strober M, Gill MK, Hunt J, Houck P, Ha W, Iyengar S, Kim E, Yen S, Hower H, Esposito-Smythers C, Goldstein T, Ryan N, Keller M. · Western Psychiatric Institute and Clinic, 3811 O'Hara St., Pittsburgh, PA 15213, USA. · Am J Psychiatry. · Pubmed #19448190 No free full text.

Abstract: OBJECTIVE: The authors sought to assess the longitudinal course of youths with bipolar spectrum disorders over a 4-year period. METHOD: At total of 413 youths (ages 7-17 years) with bipolar I disorder (N=244), bipolar II disorder (N=28), and bipolar disorder not otherwise specified (N=141) were enrolled in the study. Symptoms were ascertained retrospectively on average every 9.4 months for 4 years using the Longitudinal Interval Follow-Up Evaluation. Rates and time to recovery and recurrence and week-by-week symptomatic status were analyzed. RESULTS: Approximately 2.5 years after onset of their index episode, 81.5% of the participants had fully recovered, but 1.5 years later 62.5% had a syndromal recurrence, particularly depression. One-third of the participants had one syndromal recurrence, and 30% had two or more. The polarity of the index episode predicted that of subsequent episodes. Participants were symptomatic during 60% of the follow-up period, particularly with subsyndromal symptoms of depression and mixed polarity, with numerous changes in mood polarity. Manic symptomatology, especially syndromal, was less frequent, and bipolar II was mainly manifested by depressive symptoms. Overall, 40% of the participants had syndromal or subsyndromal symptoms during 75% of the follow-up period, and 16% of the participants experienced psychotic symptoms during 17% the follow-up period. Twenty-five percent of youths with bipolar II converted to bipolar I, and 38% of those with bipolar disorder not otherwise specified converted to bipolar I or II. Early onset, diagnosis of bipolar disorder not otherwise specified, long illness duration, low socioeconomic status, and family history of mood disorders were associated with poorer outcomes. CONCLUSIONS: Bipolar spectrum disorders in youths are characterized by episodic illness with subsyndromal and, less frequently, syndromal episodes with mainly depressive and mixed symptoms and rapid mood changes.

Wood J, Birmaher B, Axelson D, Ehmann M, Kalas C, Monk K, Turkin S, Kupfer DJ, Brent D, Monk TH, Nimgainkar VL. · Departments of Psychiatry and Human Genetics, University of Pittsburgh School of Medicine and Graduate School of Public Health, Western Psychiatric Institute and Clinic, Pittsburgh, PA, United States. · Psychiatry Res. · Pubmed #19278733 No free full text.

Abstract: Morningness/eveningness (M/E) is a stable, quantifiable measure reflecting preferred circadian phase. Two prior studies suggest that bipolar I disorder (BP1) cases are more likely to have lower M/E scores, i.e., be evening types compared with control groups. These studies did not recruit controls systematically and did not evaluate key clinical variables. We sought to replicate the reported associations in a large, well defined sample, while evaluating potential confounding factors. Adults with bipolar disorder (BP) were compared with community controls drawn randomly from the same residential areas (190 cases and 128 controls). M/E was evaluated using the composite scale of morningness (CSM). After accounting for variables correlated with M/E, BP cases had significantly lower CSM scores than controls (i.e., more evening-type or fewer morning-type). There were no significant differences in M/E scores between BP1 or BP2 disorder cases (n=134 and 56, respectively). CSM scores were stable over approximately 2 years in a subgroup of participants (n=52). Individuals prescribed anxiolytic drugs, antidepressants, antipsychotic drugs, mood stabilizers or stimulant drugs had significantly lower age-corrected CSM scores compared with persons not taking these drugs. BP cases are more likely to be evening types, suggesting circadian phase delay in BP cases. Individuals with elevated depressive mood scores are more likely to be evening types. Our results suggest a replicable relationship between circadian phase and morbid mood states.

Sala R, Axelson D, Birmaher B. · Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. · Child Adolesc Psychiatr Clin N Am. · Pubmed #19264264 No free full text.

Abstract: Pediatric bipolar disorder (BPD) significantly affects the normal emotional, cognitive, and social development. The course of children and adolescents with BPD is manifested by frequent changes in symptoms polarity showing a dimensional continuum of bipolar symptoms severity from subsyndromal to mood syndromes meeting full DSM-IV criteria. Thus, early diagnosis and treatment of pediatric bipolar is of utmost importance.

Birmaher B, Axelson D, Monk K, Kalas C, Goldstein B, Hickey MB, Obreja M, Ehmann M, Iyengar S, Shamseddeen W, Kupfer D, Brent D. · Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, 3811 O'Hara St, Pittsburgh, PA 15213-2593, USA. · Arch Gen Psychiatry. · Pubmed #19255378 No free full text.

Abstract: CONTEXT: Whether offspring of parents with bipolar disorder (BP) are at specifically high risk to develop BP and other psychiatric disorders has not been adequately studied. OBJECTIVE: To evaluate lifetime prevalence and specificity of psychiatric disorders in offspring of parents with BP-I and BP-II. DESIGN: Offspring aged 6 to 18 years who have parents with BP and community control subjects were interviewed with standardized instruments. All research staff except the statistician were blind to parental diagnoses. SETTING: Parents with BP were recruited primarily through advertisement and outpatient clinics. Control parents were ascertained by random-digit dialing and were group matched for age, sex, and neighborhood to parents with BP. PARTICIPANTS: Three hundred eighty-eight offspring of 233 parents with BP and 251 offspring of 143 demographically matched control parents. MAIN OUTCOME MEASURES: Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) Axis I disorders. RESULTS: Adjusting for demographic factors, living with 1 vs both biological parents, both biological parents' non-BP psychopathology, and within-family correlations, offspring of parents with BP showed high risk for BP spectrum disorders (odds ratio [OR] = 13.4; 95% confidence interval [CI], 2.9-61.6) and any mood (OR = 5.2; 95% CI, 2.3-11.4), anxiety (OR = 2.3; 95% CI, 1.3-4.0), and Axis I (OR = 2.2; 95% CI, 1.5-3.3) disorders. Offspring of parents with BP with high socioeconomic status showed more disruptive behavior disorders and any Axis I disorders than offspring of control parents with high socioeconomic status. Families in which both parents had BP had more offspring with BP than families with only 1 parent with BP (OR = 3.6; 95% CI, 1.1-12.2). More than 75.0% of offspring who developed BP had their first mood episode before age 12 years, with most of these episodes meeting criteria for BP not otherwise specified and, to a lesser degree, major depression. CONCLUSIONS: Offspring of parents with BP are at high risk for psychiatric disorders and specifically for early-onset BP spectrum disorders. These findings further support the familiality and validity of BP in youth and indicate a need for early identification and treatment.

Diler RS, Birmaher B, Axelson D, Goldstein B, Gill M, Strober M, Kolko DJ, Goldstein TR, Hunt J, Yang M, Ryan ND, Iyengar S, Dahl RE, Dorn LD, Keller MB. · Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. · J Child Adolesc Psychopharmacol. · Pubmed #19232020 No free full text.

Abstract: OBJECTIVES: Previous studies have suggested that the sum of Attention, Aggression, and Anxious/Depressed subscales of Child Behavior Checklist (CBCL-PBD; pediatric bipolar disorder phenotype) may be specific to pediatric bipolar disorder (BP). The purpose of this study was to evaluate the usefulness of the CBCL and CBCL-PBD to identify BP in children <12 years old. METHODS: A sample of children with BP I, II, and not otherwise specified (NOS) (n = 157) ascertained through the Course and Outcome for Bipolar Disorder in Youth (COBY) study were compared with a group of children with major depressive/anxiety disorders (MDD/ANX; n = 101), disruptive behavior disorder (DBD) (n = 127), and healthy control (HC) (n = 128). The CBCL T-scores and area under the curve (AUC) scores were calculated and compared among the above-noted groups. RESULTS: Forty one percent of BP children did not have significantly elevated CBCL-PBD scores (>or=2 standard deviations [SD]). The sensitivity and specificity of CBCL-PBD >or= 2 SD for diagnosis of BP was 57% and 70-77%, respectively, and the accuracy of CBCL-PBD for identifying a BP diagnosis was moderate (AUC = 0.72-0.78). CONCLUSION: The CBCL and the CBCL-PBD showed that BP children have more severe psychopathology than HC and children with other psychopathology, but they were not useful as a proxy for Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) diagnosis of BP.

Carlson GA, Findling RL, Post RM, Birmaher B, Blumberg HP, Correll C, DelBello MP, Fristad M, Frazier J, Hammen C, Hinshaw SP, Kowatch R, Leibenluft E, Meyer SE, Pavuluri MN, Wagner KD, Tohen M. · Department of Child and Adolescent Psychiatry, Stony Brook University School of Medicine, Stony Brook, New York, USA. · J Child Adolesc Psychopharmacol. · Pubmed #19232018 No free full text.

Abstract: OBJECTIVE: The 2006 Research Forum addressed the goal of formulating a research agenda for early-onset bipolar disorder (EOBP) and improving outcome by understanding the risk and protective factors that contribute to its severity and chronicity. METHOD: Five work groups outlined barriers and research gaps in EOBP genetics, neuroimaging, prodromes, psychosocial factors, and pharmacotherapy. RESULTS: There was agreement that the lack of consensus on the definition and diagnosis of EOBP is the primary barrier to advancing research in BP in children and adolescents. Related issues included: the difficulties in managing co-morbidity both statistically and clinically; acquiring adequate sample sizes to study the genetics, biology, and treatment; understanding the EOBP's developmental aspects; and identifying environmental mediators and moderators of risk and protection. Similarly, both psychosocial and medication treatment strategies for children with BP are hamstrung by diagnostic issues. To advance the research in EOBP, both training and funding mechanisms need to be developed with these issues in mind. CONCLUSIONS: EOBP constitutes a significant public health concern. Barriers are significant but identifiable and thus are not insurmountable. To advance the understanding of EOBP, the field must be committed to resolving diagnostic and assessment issues. Once achieved, with adequate personnel and funding resources, research into the field of EOBP will doubtless be advanced at a rapid pace.

Birmaher B, Axelson D, Strober M, Gill MK, Yang M, Ryan N, Goldstein B, Hunt J, Esposito-Smythers C, Iyengar S, Goldstein T, Chiapetta L, Keller M, Leonard H. · Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. · Bipolar Disord. · Pubmed #19133966 No free full text.

Abstract: OBJECTIVE: To compare the most severe lifetime (current or past) mood symptoms, duration of illness, and rates of lifetime comorbid disorders among youth with bipolar spectrum disorders [BP (bipolar-I, bipolar-II and bipolar-not otherwise specified)]. METHODS: A total of 173 children (<12 years) with BP, 101 adolescents with childhood-onset BP, and 90 adolescents with adolescent-onset BP were evaluated with standardized instruments. RESULTS: Depression was the most common initial and frequent episode for both adolescent groups, followed by mania/hypomania. Adolescents with childhood-onset BP had the longest illness, followed by children and then adolescents with adolescent-onset BP. Adjusting for sex, socioeconomic status, and duration of illness, while manic, both adolescent groups showed more 'typical' and severe manic symptoms. Mood lability was more frequent in childhood-onset and adolescents with early-onset BP. While depressed, both adolescent groups showed more severe depressive symptoms, higher rates of melancholic and atypical symptoms, and suicide attempts than children. Depressed children had more severe irritability than depressed adolescents. Early BP onset was associated with attention-deficit hyperactivity disorder, whereas later BP onset was associated with panic, conduct, and substance use disorders. Above-noted results were similar when each BP subtype was analyzed separately. CONCLUSIONS: Older age was associated with more severe and typical mood symptomatology. However, there were differences and similarities in type, intensity, and frequency of BP symptoms and comorbid disorders related to age of onset and duration of BP and level of psychosocial development. These factors and the normal difficulties youth have expressing and modulating their emotions may explain existing complexities in diagnosing and treating BP in youth, particular in young children, and suggest the need for developmentally sensitive treatments.

Goldstein BI, Birmaher B, Axelson DA, Goldstein TR, Esposito-Smythers C, Strober MA, Hunt J, Leonard H, Gill MK, Iyengar S, Grimm C, Yang M, Ryan ND, Keller MB. · Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. · J Clin Psychiatry. · Pubmed #19026266 No free full text.

Abstract: OBJECTIVE: Overweight/obesity is highly prevalent among adults with bipolar disorder and has been associated with illness severity. Little is known regarding overweight/obesity among youth with bipolar disorder. METHOD: Subjects were 348 youths aged 7 to 17 years who met DSM-IV criteria for bipolar I or bipolar II disorder or study-operationalized criteria for bipolar disorder not otherwise specified and were enrolled in the Course and Outcome of Bipolar Illness in Youth study. Age- and sex-adjusted body mass index was computed according to International Obesity Task Force cut points, based on self- and parent-reported height and weight, to determine overweight/obesity. The study was conducted from October 2000 to July 2006. RESULTS: Overweight/obesity was prevalent among 42% of subjects. The most robust predictors of overweight/obesity in a logistic regression model were younger age, nonwhite race, lifetime physical abuse, substance use disorders, psychiatric hospitalizations, and exposure to > or = 2 medication classes associated with weight gain. CONCLUSIONS: The prevalence of overweight/obesity among youth with bipolar disorder may be modestly greater than in the general population. Moreover, similar to adults, overweight/obesity among youth with bipolar disorder may be associated with increased psychiatric burden. These preliminary findings underscore the importance of early identification of overweight/obesity among youth with bipolar disorder. Future studies are needed to clarify the direction of the associations between overweight/obesity and the identified predictors and to compare the prevalence of overweight/obesity among youth with bipolar disorder versus other psychiatric disorders.