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Introduction There is a high incidence of Axis II personality disorders (PDs) in patients with bipolar illness, but their influence on the prospectively measured course of bipolar disorder has been less well explicated. Methods 392 outpatients with bipolar disorder gave informed consent, completed the PDQ4 99 item personality disorder rating, and where clinically rated during at least one year of prospective naturalistic treatment. They were classified as Well on admission (N = 64) or Responders (N = 146) or Non-responders (N = 182) to treatment for at least six months. Results Patients who were positive for PDs were very infrequently represented in the category of Well on admission. In addition, patients with borderline, depressive, and schizoid PDs were significantly more likely to be Non-responders compared to Responders upon prospective naturalistic treatment in the network. Conclusions Patients with bipolar disorder and comorbid PDs were in general less likely to be Well from treatment in the community at network entry or to be a Responder to prospective treatment in the network. Therapeutic approaches to patients with PDs deserve specific study in an attempt to achieve a better long-term course of bipolar disorder., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Bipolar disorder is a heritable disorder, and we aimed to assess the impact of family history of mental disorders in first-degree relatives on the severity and course of bipolar disorder., Methods: The Bipolar CHOICE (lithium versus quetiapine) and LiTMUS (optimized treatment with versus without lithium) comparative effectiveness studies were similar trials among bipolar disorder outpatients studying four different randomized treatment arms for 24 weeks. Patients self-reported on six severe mental disorders among first-degree relatives. We performed ANOVA and linear regression regarding disease severity measures, sociodemographic and cardiometabolic markers and mixed effects linear regression to evaluate treatment response., Results: Among 757 patients, 644 (85.1%) reported at least one first-degree relative with a severe mental disorder (mean=2.8; standard deviation=2.2; range=0-13). Depression (67.1%), alcohol abuse (51.0%) and bipolar disorder (47.0%) were the most frequently reported disorders. Familial psychiatric history correlated with several disease severity measures (hospitalizations, suicide attempts, and earlier onset) and sociodemographic markers (lower education and household income) but not with cardiometabolic markers (e.g. cholesterol or waist circumference) or cardiovascular risk scores, e.g. the Framingham risk score. Patients with familial psychiatric history tended to require more psychopharmacological treatment (p=0.054) but responded similarly (all p>0.1) to all four treatment arms., Conclusions: Our findings indicate that familial psychiatric history is common among outpatients with bipolar disorder and correlates with disease severity and sociodemographic measures. Patients with a greater familial psychiatric load required more intense treatment but achieved similar treatment responses compared to patients without familial psychiatric history., Competing Interests: Declaration of Competing Interest The other authors declare no competing interests., (Copyright © 2020. Published by Elsevier B.V.)

Background: There is some controversy but growing evidence that childhood onset bipolar disorder may be more prevalent and run a more difficult course in the United States than some European countries., Methods: We update and synthesize course of illness data from more than 960 outpatients with bipolar disorder (average age 40) from 4 sites in the U.S. and 3 sites in Netherlands and Germany. After giving informed consent, patients reported on parental history, childhood and lifetime stressors, comorbidities, and illness characteristics., Results: Almost all aspects of bipolar disorder were more adverse in patients from the US compared with Europe, including a significantly higher prevalence of: bipolar disorder in one parent and a mood disorder in both parents; childhood verbal, physical, or sexual abuse; stressors in the year prior to illness onset and the last episode; childhood onsets of bipolar illness; delay to first treatment; anxiety disorder, substance abuse, and medical comorbidity; mood episodes and rapid cycling; and nonresponse to prospective naturalistic treatment., Limitations: Selection bias in the recruit of patients cannot be ruled out, but convergent data in the literature suggest that this does not account for the findings. Potential mechanisms for the early onset and more adverse course in the U.S. have not been adequately delineated and require further investigation., Conclusions: The data suggest the need for earlier and more effective long-term treatment intervention in an attempt to ameliorate this adverse course and its associated heavy burden of psychiatric and medical morbidity., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Considerable data suggest that compared to some European countries, in the U.S. there are more childhood onset bipolar disorders, more adverse courses of illness, and greater treatment resistance. Psychosocial variables related to these findings have not been adequately explored. Therefore we analyzed psychosocial stressors in three time domains: childhood; the year prior to illness Onset; and the Last Episode from questionnaires in 968 outpatients (mean age 41) with bipolar I or II disorder; 676 from four sites in the U.S. and 292 from three in the Netherlands and Germany (abbreviated here as Europe). Compared to the Europeans, those from the U.S. had significantly more stressors in childhood and prior to the last episode. Stressors prior to the last episode were related to: childhood stressors; an earlier age at illness onset; anxiety and substance abuse comorbidity; lower income; both parents having an affective illness; and feeling more stigma. These data suggest a greater prevalence of adverse life events in childhood and over the course of bipolar illness in the U.S. compared to the Netherlands and Germany. Clinical, therapeutic, and public health approaches to these illness-relevant stressors require further exploration., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Introduction: This study was undertaken to evaluate the prevalence rate of anxiety comorbidity in bipolar subjects with and without alcohol use disorders (AUD)., Methods: Bipolar men and women who entered the Stanley Foundation Bipolar Network (SFBN) underwent a Structured Clinical Interview for DSM-IV (SCID-IV) and were divided into those subjects meeting current or lifetime criteria for an alcohol use disorder (AUD=213) vs. those subjects who did not (non-AUD=137). Lifetime rates of comorbid anxiety disorder were evaluated between groups., Results: Of 350 subjects, 163 (46.5%) met criteria for an anxiety disorder. Panic disorder and OCD were the most common anxiety disorders in the AUD and non-AUD groups. OCD and specific phobia were significantly less prevalent in BP I patients with AUD compared to those without. Bipolar women with AUD had a significantly higher rate of PTSD than those without., Conclusion: These data highlight the added liability of anxiety comorbidity in BP disorder. Specifically, the greater amount of PTSD and lesser amount of OCD in bipolar women with alcohol comorbidity may have important diagnostic and treatment implications beyond dual diagnosis. Further study in comorbidity patterns is encouraged to not only better understand illness burden, but to maximize pattern-specific treatment outcomes.

Background: The objective of this retrospective chart review was to evaluate the phenomenology and response to divalproex in a sub-population of children admitted to an inpatient setting with severe impairing symptoms of irritability and aggression. In addition, we examined whether the symptomatology of this group was consistent with a pediatric divalproex-responsive bipolar spectrum disorder., Methods: The charts of 46 child and adolescent patients with prominent impulsive aggression with irritability admitted to a crisis stabilization center were assessed retrospectively. Impulsive aggressive symptoms were assessed for admission and discharge severity by two clinicians using the Overt Aggression Scale (OAS) and the Anger-Hostility Subscale of the SCL-90 (SCL-A), with overall functioning changes assessed using the Children's Global Assessment Scale (C-GAS)., Results: Statistically significant improvements were obtained for the group in the C-GAS, with significant decreases in the OAS and the SCL-A scores at discharge, following a maximal 14-day stay. No severe side effects were reported. All patients met the criteria for a potential pediatric bipolar phenotype., Limitations: This was a retrospective study without randomization or a control group. Additionally, the non-blinded design may have biased the raters concerning the effectiveness of divalproex for impulsive aggression., Conclusions: Our data are in line with divalproex response in children and adolescents with target symptoms of explosive temper and mood instability. Our data further suggest that such symptoms, coupled with impulsive aggression and irritability, as well as related manic symptoms, constitute a pediatric divalproex-responsive bipolar spectrum disorder.