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American Journal of Psychiatry | 2009

Four-Year Longitudinal Course of Children and Adolescents With Bipolar Spectrum Disorders: The Course and Outcome of Bipolar Youth (COBY) Study

Boris Birmaher; David Axelson; Benjamin I. Goldstein; Michael Strober; Mary Kay Gill, , M.S.N.; Jeffrey Hunt; M.S.H. Patricia R. Houck; Wonho Ha; Satish Iyengar; Eunice Kim; Shirley Yen; M.S.W. Heather Hower; Christianne Esposito-Smythers; Tina R. Goldstein; Neal D. Ryan; Martin B. Keller

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.


Journal of the American Academy of Child and Adolescent Psychiatry | 2011

Course of subthreshold bipolar disorder in youth: diagnostic progression from bipolar disorder not otherwise specified.

David Axelson; Boris Birmaher; Michael Strober; Benjamin I. Goldstein; Wonho Ha; Mary Kay Gill; Tina R. Goldstein; Shirley Yen; Heather Hower; Jeffrey Hunt; Fangzi Liao; Satish Iyengar; Daniel P. Dickstein; Eunice Kim; Neal D. Ryan; Erica Frankel; Martin B. Keller

OBJECTIVE To determine the rate of diagnostic conversion from an operationalized diagnosis of bipolar disorder not otherwise specified (BP-NOS) to bipolar I disorder (BP-I) or bipolar II disorder (BP-II) in youth over prospective follow-up and to identify factors associated with conversion. METHOD Subjects were 140 children and adolescents recruited from clinical referrals or advertisement who met operationalized criteria for BP-NOS at intake and participated in at least one follow-up evaluation (91% of initial cohort). Diagnoses were assessed at follow-up interviews using the Longitudinal Interval Follow-Up Evaluation. The mean duration of follow-up was 5 years and the mean interval between assessments was 8.2 months. RESULTS Diagnostic conversion to BP-I or BP-II occurred in 63 subjects (45%): 32 (23%) to BP-I (nine of whom had initially converted to BP-II) and 31 to only BP-II (22%). Median time from intake to conversion was 58 weeks. First- or second-degree family history of mania or hypomania was the strongest baseline predictor of diagnostic conversion (p = .006). Over follow-up, conversion was associated with greater intensity of hypomanic symptoms and with greater exposure to specialized, intensive outpatient psychosocial treatments. There was no association between conversion and exposure to treatment with particular medication classes. CONCLUSIONS Children and adolescents referred with mood symptoms that meet operationalized criteria for BP-NOS, particularly those with a family history of BP, frequently progress to BP-I or BP-II. Efforts to identify these youth and effectively intervene may have the potential to curtail the progression of mood disorders in this high-risk population.


Journal of Affective Disorders | 2009

Psychosocial Functioning Among Bipolar Youth

Tina R. Goldstein; Boris Birmaher; David Axelson; Benjamin I. Goldstein; Mary Kay Gill; Christianne Esposito-Smythers; Neal D. Ryan; Michael Strober; Jeffrey Hunt; Martin B. Keller

BACKGROUND Evidence indicates that children and adolescents with bipolar disorder (BP) experience significant functional impairment. However, little is known about the association between psychosocial functioning and episodes of illness, demographic, and clinical variables in this population. METHODS Subjects included 446 patients aged 7 to 17 diagnosed with DSM-IV bipolar disorder via the K-SADS for the Course and Outcome of Bipolar Youth (COBY) study. The Psychosocial Functioning Schedule of the Adolescent Longitudinal Interval Follow-Up Assessment (A-LIFE) was administered at study intake. RESULTS Mild to moderate levels of psychosocial impairment were evident in work (includes academics), interpersonal, and overall domains of functioning among BP youth. Multivariate analyses indicated that the strongest predictors of psychosocial impairment were adolescence (regardless of age of onset), current mood episode, current affective symptom severity, current psychotic symptoms, and current comorbid conduct disorder. Bipolar youth in-episode were significantly more impaired than those in partial remission/recovery in every functional domain examined and were less satisfied with their functioning. Yet, BP youth in partial remission/recovery reported significant psychosocial impairment. LIMITATIONS Limitations include the reliance on patient and parent retrospective report of psychosocial functioning. Additionally, we did not account for the impact of psychosocial and pharmacological interventions on functioning. CONCLUSIONS Findings suggest pediatric BP is associated with significant impairment in psychosocial functioning during and between episodes, with greater impairment during mood episodes than during partial remission/recovery. Additionally, functional impairment in BP appears to increase during adolescence regardless of age of onset. Clinicians should carefully assess and address psychosocial impairment during and between mood episodes, with particular attention to the functioning of BP adolescents.


Bipolar Disorders | 2008

Substance Use Disorders among Adolescents with Bipolar Spectrum Disorders

Benjamin I. Goldstein; Michael Strober; Boris Birmaher; David Axelson; Christianne Esposito-Smythers; Tina R. Goldstein; Henrietta L. Leonard; Jeffrey Hunt; Mary Kay Gill; Satish Iyengar; Colleen Grimm; Mei Yang; Neal D. Ryan; Martin B. Keller

OBJECTIVE We set out to examine the prevalence and correlates of substance use disorders (SUD) in a large sample of adolescents with bipolar disorder (BP). METHODS Subjects were 249 adolescents ages 12 to 17 years old who fulfilled DSM-IV criteria for bipolar I disorder [(BPI), n = 154], or bipolar II disorder [(BPII), n = 25], or operationalized criteria for BP not otherwise specified [(BP NOS), n = 70], via the Schedule for Affective Disorders and Schizophrenia for School-Aged Children (K-SADS). As part of the multi-site Course and Outcome of Bipolar Youth study, demographic, clinical, and family history variables were measured via intake clinical interview with the subject and a parent/guardian. RESULTS The lifetime prevalence of SUD among adolescents with BP was 16% (40/249). Results from univariate analyses indicated that subjects with, as compared to without, SUD were significantly less likely to be living with both biological parents, and that there was significantly greater lifetime prevalence of physical abuse, sexual abuse, suicide attempts, conduct disorder, and posttraumatic stress disorder among subjects with SUD. Subjects with SUD reported significantly greater 12-month prevalence of trouble with police, and females with SUD reported significantly greater 12-month prevalence of pregnancy and abortion. Significant predictors of SUD in a logistic regression model included living with both biological parents (lower prevalence), conduct disorder and suicide attempts (increased prevalence). In logistic regression analyses controlling for demographic differences and conduct disorder, SUD remained significantly associated with trouble with police, whereas the association of SUD with pregnancy and abortion was reduced to a statistical trend. The prevalence of SUD was not significantly different among child- versus adolescent-onset BP subjects. CONCLUSIONS SUD among adolescents with BP is associated with profound hazards including suicide attempts, trouble with police, and teenage pregnancy and abortion.


Journal of Consulting and Clinical Psychology | 2011

Treatment of co-occurring substance abuse and suicidality among adolescents: a randomized trial.

Christianne Esposito-Smythers; Anthony Spirito; Christopher W. Kahler; Jeffrey Hunt; Peter M. Monti

OBJECTIVE This study tested a cognitive-behavioral treatment protocol for adolescents with a co-occurring alcohol or other drug use disorder (AOD) and suicidality in a randomized clinical trial. METHOD Forty adolescents (Mage = 15 years; 68% female, 89% White) and their families recruited from an inpatient psychiatric hospital were randomly assigned to an integrated outpatient cognitive-behavioral intervention for co-occurring AOD and suicidality (I-CBT) or enhanced treatment as usual (E-TAU). Primary measures include the Schedule for Affective Disorders and Schizophrenia for School-Age Children, Suicide Ideation Questionnaire, Columbia Impairment Scale, Timeline Followback, Rutgers Alcohol Problem Index, and Rutgers Marijuana Problem Index. Assessments were completed at pretreatment as well as 3, 6, 12, and 18 months postenrollment. RESULTS In intent-to-treat analyses, I-CBT was associated with significantly fewer heavy drinking days and days of marijuana use relative to E-TAU but not with fewer drinking days. Those randomized to I-CBT in comparison to E-TAU also reported significantly less global impairment as well as fewer suicide attempts, inpatient psychiatric hospitalizations, emergency department visits, and arrests. Adolescents across groups showed equivalent reductions in suicidal ideation. CONCLUSIONS I-CBT for adolescents with co-occurring AOD and suicidality is associated with significant improvement in both substance use and suicidal behavior, as well as markedly decreased use of additional health services including inpatient psychiatric hospitalizations and emergency department visits. Further testing of integrated protocols for adolescent AOD and suicidality with larger and more diverse samples is warranted.


Journal of Child and Adolescent Psychopharmacology | 2009

The Child Behavior Checklist (CBCL) and the CBCL-Bipolar Phenotype Are Not Useful in Diagnosing Pediatric Bipolar Disorder

Rasim Somer Diler; Boris Birmaher; David Axelson; Ben Goldstein; MaryKay Gill; Michael Strober; David J. Kolko; Tina R. Goldstein; Jeffrey Hunt; Mei Yang; Neal D. Ryan; Satish Iyengar; Ronald E. Dahl; Lorah D. Dorn; Martin B. Keller

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.


Journal of Affective Disorders | 2009

Prevalence and correlates of physical and sexual abuse in children and adolescents with bipolar disorder

Soledad Romero; Boris Birmaher; David Axelson; Tina R. Goldstein; Benjamin I. Goldstein; Mary Kay Gill; Ana Maria Iosif; Michael Strober; Jeffrey Hunt; Christianne Esposito-Smythers; Neal D. Ryan; Henrietta L. Leonard; Martin B. Keller

OBJECTIVE Adult bipolar disorder (BP) has been associated with lifetime history of physical and sexual abuse. However, there are no reports of the prevalence of abuse in BP youth. The objective of this study was to examine the prevalence and correlates of physical and/or sexual abuse among youth with BP spectrum disorders. METHODS Four hundred forty-six youths, ages 7 to 17 years (12.7+/-3.2), meeting DSM-IV criteria for BP-I (n=260), BP-II (n=32) or operationalized definition of BP-NOS (n=154) were assessed using the Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime version (K-SADS-PL). Abuse was ascertained using the K-SADS. RESULTS Twenty percent of the sample experienced physical and/or sexual abuse. The most robust correlates of any abuse history were living with a non-intact family (OR=2.6), lifetime history of posttraumatic stress disorder (PTSD) (OR=8.8), psychosis (OR=2.1), conduct disorder (CD) (OR=2.3), and first-degree family history of mood disorder (OR=2.2). After adjusting for confounding demographic factors, physical abuse was associated with longer duration of BP illness, non-intact family, PTSD, psychosis, and first-degree family history of mood disorder. Sexual abuse was associated with PTSD. Subjects with both types of abuse were older, with longer illness duration, non-intact family, and greater prevalence of PTSD and CD as compared with the non-abused group. LIMITATIONS Retrospective data. Also, since this is a cross-sectional study, no inferences regarding causality can be made. CONCLUSION Sexual and/or physical abuse is common in youth with BP particularly in subjects with comorbid PTSD, psychosis, or CD. Prompt identification and treatment of these youth is warranted.


American Journal on Addictions | 2008

Significance of cigarette smoking among youths with bipolar disorder

Benjamin I. Goldstein; Boris Birmaher; David Axelson; Tina R. Goldstein; Christianne Esposito-Smythers; Michael Strober; Jeffrey Hunt; Henrietta L. Leonard; Mary Kay Gill; Satish Iyengar; Colleen Grimm; Mei Yang; Neal D. Ryan; Martin B. Keller

Cigarette smoking among adults with bipolar disorder (BP) correlates with psychosis, substance use disorders (SUD), and suicidality. Little is known regarding smoking among youths with BP. Youths with BP (n = 441) were divided into three smoking groups: Never, Ever, and Daily. Twenty-five percent reported any smoking (11% daily, 14% ever). Ever and Daily subjects had significantly greater lifetime prevalence of suicide attempts, physical abuse, conduct disorder, and SUD compared to Never subjects. Daily heavy smokers had greater prevalence of SUD and suicide attempts, and worse depression versus daily light smokers. Smoking among youths with BP is independently associated with suicide attempts and SUD.


The Journal of Clinical Psychiatry | 2010

Comorbid anxiety in children and adolescents with bipolar spectrum disorders: prevalence and clinical correlates.

Regina Sala; David Axelson; Josefina Castro-Fornieles; Tina R. Goldstein; Wonho Ha; Fangzi Liao; Mary Kay Gill; Satish Iyengar; Michael Strober; Benjamin I. Goldstein; Shirley Yen; Heather Hower; Jeffrey Hunt; Neal D. Ryan; Daniel P. Dickstein; Martin B. Keller; Boris Birmaher

OBJECTIVE Anxiety disorders are among the most common comorbid conditions in youth with bipolar disorder. We aimed to examine the prevalence and correlates of comorbid anxiety disorders among youth with bipolar disorder. METHOD As part of the Course and Outcome of Bipolar Youth study, 446 youth, ages 7 to 17 years, who met DSM-IV criteria for bipolar I disorder (n = 260) or bipolar II disorder (n = 32) or met operationalized criteria for bipolar disorder not otherwise specified (n = 154) were included. Subjects were evaluated for current and lifetime Axis I psychiatric disorders at intake using the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime version, and standardized instruments were used to assess functioning and family history. RESULTS Forty-four percent (n = 194) of the sample met DSM-IV criteria for at least 1 lifetime anxiety disorder, most commonly separation anxiety (24%) and generalized anxiety disorders (16%). Nearly 20% met criteria for 2 or more anxiety disorders. Overall, anxiety disorders predated the onset of bipolar disorder. Subjects with bipolar II disorder were more likely than subjects with bipolar I disorder or bipolar disorder not otherwise specified to have a comorbid anxiety disorder. After adjusting for confounding factors, youth with bipolar disorder with anxiety were more likely to have bipolar II disorder; longer duration of mood symptoms; more severe ratings of depression; and family history of depression, hopelessness, and somatic complaints during their worst lifetime depressive episode than those without anxiety. CONCLUSIONS Comorbid anxiety disorders are common in youth with bipolar disorder, and they most often predate bipolar disorder onset. Bipolar II disorder, a family history of depression, and more severe lifetime depressive episodes distinguish youth with bipolar disorder with comorbid anxiety disorders from those without. Careful consideration should be given to the assessment of comorbid anxiety in youth with bipolar disorder.


Journal of Affective Disorders | 2010

Clinical and psychosocial correlates of non-suicidal self-injury within a sample of children and adolescents with bipolar disorder

Christianne Esposito-Smythers; Tina R. Goldstein; Boris Birmaher; Benjamin I. Goldstein; Jeffrey Hunt; Neal D. Ryan; David Axelson; Michael Strober; Mary Kay Gill; Andrea Hanley; Martin B. Keller

BACKGROUND The purpose of this study is to examine the prevalence and correlates of non-suicidal self-injury (NSSI) among children and adolescents diagnosed with bipolar disorder (BP). METHODS Four hundred-thirty two youth with a diagnosis of BP and their parents, including 193 children and 239 adolescents, completed a diagnostic interview and instruments to assess youth clinical and illness history, youth comorbidity, parental mood disorder, and psychosocial functioning. RESULTS Approximately 22% of children and 22% of adolescents reported NSSI during the course of their most recent mood episode. In a multivariate model controlling for global impairment, among children, a BPI or BPII diagnosis (versus BPNOS), psychosis, separation anxiety disorder, and greater severity of depressive symptoms were found to be associated with NSSI. Among adolescents, a mixed episode, a suicide attempt, greater severity of depressive symptoms, and poor psychosocial functioning were found to be associated with NSSI. Neither the presence of a youth comorbid disruptive behavior disorder nor a parental mood disorder was associated with NSSI. LIMITATIONS The primary limitations of this study include the use of a cross-sectional study design, lack of a control group, and limited generalizability of study results to non-clinical and ethnically diverse samples. CONCLUSIONS NSSI is not uncommon among youth with BP, particularly those who present with BPI or BPII, psychosis, a mixed episode, suicidal behavior, severe depressive symptoms, separation anxiety, and/or poor psychosocial functioning. However, the relative importance of these factors in relation to NSSI may vary with age. Treatments for BP that are developmentally sensitive, examine the function of NSSI for each youth, and teach adaptive skills to address emotional and social needs, may prove to be most successful.

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Boris Birmaher

University of Texas Southwestern Medical Center

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David Axelson

Nationwide Children's Hospital

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Mary Kay Gill

University of Pittsburgh

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Benjamin I. Goldstein

University of Texas Southwestern Medical Center

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