Benjamin I. Goldstein

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

OBJECTIVEnTo 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.nnnMETHODnSubjects 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.nnnRESULTSnDiagnostic 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.nnnCONCLUSIONSnChildren 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.

Inflammation in Children and Adolescents With Neuropsychiatric Disorders: A Systematic Review

OBJECTIVEnThere has been rapid growth in research regarding inflammation in neuropsychiatric disorders as it relates to youth. We therefore set out to systematically review the literature on inflammation and neuropsychiatric disorders in children and adolescents.nnnMETHODnA systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were included if proinflammatory markers (PIMs) in children and/or adolescents with neuropsychiatric disorders were measured.nnnRESULTSnSixty-seven studies were included, involving 3,952 youth. Evidence for a proinflammatory state is strongest for autism spectrum disorders (ASD). PIMs are elevated in children and adolescents with major depressive disorder (MDD), bipolar disorder (BD), post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), Tourettes disorder (TD), attention-deficit/hyperactivity disorder (ADHD), and schizophrenia (SZ). However, the data are inconsistent. Evidence for specific PIMs is equivocal at this stage, although the findings in youth with MDD, BD, and PTSD converge with the extant adult literature in these areas. Definitive conclusions are limited by methodologic factors including cross-sectional and retrospective study design, between-study differences in specific markers and methods of analysis, small sample size, and other sources of heterogeneity.nnnCONCLUSIONnThe literature regarding inflammation among children and adolescents with neuropsychiatric disorders represents nearly 4,000 youth. There is preliminary evidence for elevated markers of inflammation in this population. Larger, prospective studies are needed to realize the goal of inflammatory markers informing clinical practice. In the interim, present findings suggest that further examination of this topic is warranted.

The burden of obesity among adults with bipolar disorder in the United States

Goldstein BI, Liu S‐M, Zivkovic N, Schaffer A, Chien L‐C, Blanco C. The burden of obesity among adults with bipolar disorder in the United States.u2028Bipolar Disord 2011: 13: 387–395.

The specific burden of comorbid anxiety disorders and of substance use disorders in bipolar I disorder

OBJECTIVESnUncertainty exists regarding whether comorbid substance use disorders (SUDs) in bipolar I disorder are more prevalent among persons with versus without comorbid anxiety disorders. Moreover, the independent contribution of these comorbidities to the burden of bipolar disorder (BD) is unclear.nnnMETHODSnThe 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions was used to identify respondents with lifetime BD (n = 1,411). Illness severity was compared across four groups based on the presence of lifetime anxiety disorders, lifetime SUDs, neither, or both. Variables included lifetime prevalence of mixed mania, prolonged mood episodes, BD-related health service utilization, and forensic history, 12-month prevalence of mania and depression, and current general mental health functioning. Diagnoses were generated using the National Institute on Alcohol Abuse and Alcoholism Alcohol Use Disorder and Associated Disabilities Interview Schedule, DSM-IV Version. Analyses were computed separately for males and females.nnnRESULTSnFor females only, the lifetime prevalence of SUDs was significantly greater among those with lifetime anxiety disorders [odds ratio (OR) = 1.41, 95% confidence interval (CI) = 1.08-1.86]; this was not found among males (OR = 1.15, 95% CI = 0.79-1.68). In multiple logistic regression analyses among both males and females, anxiety disorders were significantly associated with mixed episodes, prolonged depressive episodes, 12-month prevalence of depression, BD-related health service utilization, and poorer current mental health functioning. SUDs were significantly associated with mixed episodes among females, 12-month prevalence of depression among males, and with forensic history among both males and females.nnnCONCLUSIONSnWhereas comorbid anxiety disorders appear to confer increased liability towards poor mental health functioning and greater BD-related health service utilization, comorbid SUDs are associated with positive forensic history. Early identification and treatment of these comorbid conditions are of paramount importance. Further representative prospective studies are needed.

Self-harm Emergencies After Bariatric Surgery: A Population-Based Cohort Study

IMPORTANCEnSelf-harm behaviors, including suicidal ideation and past suicide attempts, are frequent in bariatric surgery candidates. It is unclear, however, whether these behaviors are mitigated or aggravated by surgery.nnnOBJECTIVEnTo compare the risk of self-harm behaviors before and after bariatric surgery.nnnDESIGN, SETTING, AND PARTICIPANTSnIn this population-based, self-matched, longitudinal cohort analysis, we studied 8815 adults from Ontario, Canada, who underwent bariatric surgery between April 1, 2006, and March 31, 2011. Follow-up for each patient was 3 years prior to surgery and 3 years after surgery.nnnMAIN OUTCOMES AND MEASURESnSelf-harm emergencies 3 years before and after surgery.nnnRESULTSnThe cohort included 8815 patients of whom 7176 (81.4%) were women, 7063 (80.1%) were 35 years or older, and 8681 (98.5%) were treated with gastric bypass. A total of 111 patients had 158 self-harm emergencies during follow-up. Overall, self-harm emergencies significantly increased after surgery (3.63 per 1000 patient-years) compared with before surgery (2.33 per 1000 patient-years), equaling a rate ratio (RR) of 1.54 (95% CI,u20091.03-2.30; Pu2009=u2009.007). Self-harm emergencies after surgery were higher than before surgery among patients older than 35 years (RR,u20091.76; 95% CI,u20091.05-2.94; P = .03), those with a low-income status (RR,u20092.09; 95% CI,u20091.20-3.65; P = .01), and those living in rural areas (RR,u20096.49; 95% CI,u20091.42-29.63; P = .02). The most common self-harm mechanism was an intentional overdose (115 [72.8%]). A total of 147 events (93.0%) occurred in patients diagnosed as having a mental health disorder during the 5 years before the surgery.nnnCONCLUSIONS AND RELEVANCEnIn this study, the risk of self-harm emergencies increased after bariatric surgery, underscoring the need for screening for suicide risk during follow-up.

Anti-inflammatory agents in the treatment of bipolar depression: a systematic review and meta-analysis

Inflammation has been implicated in the risk, pathophysiology, and progression of mood disorders and, as such, has become a target of interest in the treatment of bipolar disorder (BD). Therefore, the objective of the current qualitative and quantitative review was to determine the overall antidepressant effect of adjunctive anti‐inflammatory agents in the treatment of bipolar depression.

COURSE OF COMORBID ANXIETY DISORDERS AMONG ADULTS WITH BIPOLAR DISORDER IN THE U.S. POPULATION

OBJECTIVEnTo examine the prevalence and correlates of comorbid anxiety disorders among individuals with bipolar disorders (BP) and their association with prospectively ascertained comorbidities, treatment, and psychosocial functioning.nnnMETHODnAs part of the National Epidemiologic Survey on Alcohol and Related Conditions, 1600 adults who met lifetime DSM-IV criteria for BP-I (nxa0=xa01172) and BP-II (nxa0=xa0428) were included. Individuals were evaluated using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DMS-IV Version and data was analyzed from Waves 1 and 2, approximately 3 years apart.nnnRESULTSnSixty percent of individuals with BP had at least one lifetime comorbid anxiety disorder. Individuals with BP and anxiety disorders shared lifetime risk factors for major depressive disorder and had prospectively more depressive and manic/hypomanic episodes, suicidal ideation, suicide attempts, and more treatment seeking than those without anxiety. During the follow-up, higher incidence of panic disorder, drug use disorders, and lower psychosocial functioning were found in individuals with BP with versus without anxiety disorders.nnnCONCLUSIONSnAnxiety disorders are prospectively associated with elevated BP severity and BP-related mental health service use. Early identification and treatment of anxiety disorders are warranted to improve the course and outcome of individuals with BP.

Differentiating between Bipolar Disorder Types I and II: Results from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC)

OBJECTIVEnBipolar Disorder I (BD I) and Bipolar Disorder II (BD II) vary considerably, with differences in symptomatology, management and prognosis. For patients with depression, the distinction between BD I and BD II is not always apparent, and hinges on the differentiation between manic/mixed and hypomanic episodes. Other putative differences between patients with BD I and II exist and may assist in distinguishing between these two conditions.nnnMETHODSnData were obtained from the National Epidemiological Survey on Alcohol and Related Conditions. A total of 1429 subjects were included in our analysis based on DSM-IV criteria, 935 with BD I and 494 with BD II. We examined for differences in a number of variables including demographics, clinical features, depressive symptoms, and co-morbid conditions using t-tests and chi-square analyses for a comparison of means as well as a logistic regression for variables found to be significant.nnnRESULTSnKey differences between BD I and BD II were identified in all categories in our comparison of means. In the regression analysis, a number of variables were determined to be predictors of BD I, including unemployment (OR=0.6), taking medications for depression (OR=1.7), a history of a suicide attempt (OR=1.8), depressive symptoms such as weight gain (OR=1.7), fidgeting (OR=1.5), feelings of worthlessness (OR=1.6) and difficulties with responsibilities (OR=2.2), as well as the presence of specific phobias (OR=1.8) and Cluster C traits (OR=1.4).nnnCONCLUSIONSnOur results indicate that in addition to the differences between manic/mixed and hypomanic episodes, other significant differences exist that may be used to help differentiate BD I from BD II.

Disruptive Mood Dysregulation Disorder and Chronic Irritability in Youth at Familial Risk for Bipolar Disorder

OBJECTIVEnDisruptive mood dysregulation disorder (DMDD) is a new diagnosis in the DSM-5. Youth with a family history of bipolar disorder (BD) are at increased risk for BD and non-bipolar psychopathology. No studies to date have examined rates of DMDD among offspring of parents with BD. This study examines the risk for DMDD in offspring of parents with BD compared to community controls and considers rates of chronic irritability (independent of a DMDD diagnosis) across diagnoses in youth with parents with BD.nnnMETHODnModified DMDD criteria were applied post hoc to 375 offspring of parents with BD and 241 offspring, aged 6 to 17 years, of community control parents. We calculated odds ratios using generalized linear mixed models.xa0Inxa0addition, we explored associations with a severe chronic irritability phenotype andxa0variousxa0diagnoses in the high-risk cohort.nnnRESULTSnOffspring of parents with BD were more likely to meet criteria for DMDD than were the offspring of community control parents (Odds ratio [OR]xa0= 8.3, 6.7% vs. 0.8%), even when controlling for demographic variables and comorbid parental diagnoses (ORxa0= 5.4). They also had higher rates of chronic irritability compared to community controls (12.5% vs. 2.5%, χ(2)xa0= 18.8, pxa0< .005). Within the offspring of parents withxa0BD, the chronic irritability phenotype was frequently present in offspring with diagnosesxa0ofxa0BD,xa0depression, attention-deficit/hyperactivity disorder, and disruptive behavior disorders.nnnCONCLUSIONSnLike other non-BD diagnoses, family history of BD increases the risk for DMDD. Severe chronic irritability and temper tantrums are the core features of DMDD, and are associated with mood and behavioral disorders in youth at risk for BD.

Dimensional psychopathology in offspring of parents with bipolar disorder.

Diler RS, Birmaher B, Axelson D, Obreja M, Monk K, Hickey MB, Goldstein B, Goldstein T, Sakolsky D, Iyengar S, Brent D, Kupfer D. Dimensional psychopathology in offspring of parents with bipolar disorder. Bipolar Disord 2011: 13: 670–678.