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Characteristics of Bipolar I patients grouped by externalizing disorders.

ABSTRACT: BACKGROUND:Bipolar disorder co-occurs with a number of disorders with externalizing features. The aim of this study is to determine whether Bipolar I (BPI) subjects with comorbid externalizing disorders and a subgroup with externalizing symptoms prior to age 15 have different clinical features than those without externalizing disorders and whether these could be attributed to specific genetic variations. METHODS:A large cohort (N=2505) of Bipolar I subjects was analyzed. Course of illness parameters were compared between an Externalizing Group, an Early-Onset Subgroup and a Non-Externalizing Group in the Discovery sample (N=1268). Findings were validated using an independent set of 1237 BPI subjects (Validation sample). Genetic analyses were carried out. RESULTS:Subjects in the Externalizing Group (and Early-Onset Subgroup) tended to have a more severe clinical course, even in areas specifically related to mood disorder such as cycling frequency and rapid mood switching. Regression analysis showed that the differences are not completely explainable by substance use. Genetic analyses identified nominally associated SNPs; calcium channel genes were not enriched in the gene variants identified. LIMITATIONS:Validation in independent samples is needed to confirm the genetic findings in the present study. CONCLUSIONS:Our findings support the presence of an externalizing disorder subphenotype within BPI with greater severity of mood disorder and possible specific genetic features.

SUBMITTER: Swaminathan S

PROVIDER: S-EPMC4433475 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Characteristics of Bipolar I patients grouped by externalizing disorders.

Swaminathan Shanker S Koller Daniel L DL Foroud Tatiana T Edenberg Howard J HJ Xuei Xiaoling X Niculescu Alexander B AB Nurnberger John I JI

Journal of affective disorders 20150314

<h4>Background</h4>Bipolar disorder co-occurs with a number of disorders with externalizing features. The aim of this study is to determine whether Bipolar I (BPI) subjects with comorbid externalizing disorders and a subgroup with externalizing symptoms prior to age 15 have different clinical features than those without externalizing disorders and whether these could be attributed to specific genetic variations.<h4>Methods</h4>A large cohort (N=2505) of Bipolar I subjects was analyzed. Course of ...[more]

PMID: 25827505

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Project description:Objectives: Bipolar disorder (BD) is a debilitating illness that often starts at an early age. Prevention of first and subsequent mood episodes, which are usually preceded by a period characterized by subthreshold symptoms is important. We compared demographic and clinical characteristics including severity and duration of subsyndromal symptoms across adolescents with three different bipolar-spectrum disorders. Methods: Syndromal and subsyndromal psychopathology were assessed in adolescent inpatients (age = 12-18 years) with a clinical mood disorder diagnosis. Assessments included the validated Bipolar Prodrome Symptom Interview and Scale-Prospective (BPSS-P). We compared phenomenology across patients with a research consensus conference-confirmed DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) diagnoses of BD-I, BD-not otherwise specified (NOS), or mood disorder (MD) NOS. Results: Seventy-six adolescents (age = 15.6 ± 1.4 years, females = 59.2%) were included (BD-I = 24; BD-NOS = 29; MD-NOS = 23) in this study. Median baseline global assessment of functioning scale score was 21 (interquartile range = 17-40; between-group p = 0.31). Comorbidity was frequent, and similar across groups, including disruptive behavior disorders (55.5%, p = 0.27), anxiety disorders (40.8%, p = 0.98), and personality disorder traits (25.0%, p = 0.21). Mania symptoms (most frequent: irritability = 93.4%, p = 0.82) and depressive symptoms (most frequent: depressed mood = 81.6%, p = 0.14) were common in all three BD-spectrum groups. Manic and depressive symptoms were more severe in both BD-I and BD-NOS versus MD-NOS (p < 0.0001). Median duration of subthreshold manic symptoms was shorter in MD-NOS versus BD-NOS (11.7 vs. 20.4 weeks, p = 0.002) and substantial in both groups. The most used psychotropics upon discharge were antipsychotics (65.8%; BD-I = 79.2%; BD-NOS = 62.1%; MD-NOS = 56.5%, p = 0.227), followed by mood stabilizers (43.4%; BD-I = 66.7%; BD-NOS = 31.0%; MD-NOS = 34.8%, p = 0.02) and antidepressants (19.7%; BD-I = 20.8%; BD-NOS = 10.3%; MD-NOS = 30.4%). Conclusions: Youth with BD-I, BD-NOS, and MD-NOS experience considerable symptomatology and are functionally impaired, with few differences observed in psychiatric comorbidity and clinical severity. Moreover, youth with BD-NOS and MD-NOS undergo a period with subthreshold manic symptoms, enabling identification and, possibly, preventive intervention of those at risk for developing BD or other affective episodes requiring hospitalization.

Project description:ObjectiveThe risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders.MethodAn expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder.ResultsThere is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder.ConclusionsBecause of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications.

Project description:BackgroundThe laboratory diagnosis of hereditary spherocytosis commonly relies on NaCl-based or glycerol-based red cell osmotic fragility tests; more recently, an assay directly targeting the hereditary spherocytosis molecular defect (eosin-5'-maleimide-binding test) has been proposed. None of the available tests identifies all cases of hereditary spherocytosis.Design and methodsWe compared the performances of the eosin-5'-maleimide-binding test, NaCl-osmotic fragility studies on fresh and incubated blood, the glycerol lysis test, the acidified glycerol lysis test, and the Pink test on a series of 150 patients with hereditary spherocytosis grouped according to clinical phenotype and the defective protein, with the final aim of finding the combination of tests associated with the highest diagnostic power, even in the mildest cases of hereditary spherocytosis.ResultsThe eosin-5'-maleimide-binding test had a sensitivity of 93% and a specificity of 98% for detecting hereditary spherocytosis: the sensitivity was independent of the type and amount of molecular defect and of the clinical phenotype. The acidified glycerol lysis test and Pink test showed comparable sensitivity (95% and 91%). The sensitivity of NaCl osmotic fragility tests, commonly considered the gold standard for the diagnosis of hereditary spherocytosis, was 68% on fresh blood and 81% on incubated blood, and further decreased in compensated cases (53% and 64%, respectively). The combination of the eosin-5'-maleimide-binding test and acidified glycerol lysis test enabled all patients with hereditary spherocytosis to be identified. The eosin-5'-maleimide-binding test showed the greatest disease specificity.ConclusionsEach type of test fails to diagnose some cases of hereditary spherocytosis. The association of an eosin-5'-maleimide-binding test and an acidified glycerol lysis test enabled identification of all patients with hereditary spherocytosis in this series and, therefore, represents a currently effective diagnostic strategy for hereditary spherocytosis including mild/compensated cases.

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Characteristics of Bipolar I patients grouped by externalizing disorders.

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Characteristics of Bipolar I patients grouped by externalizing disorders.

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