Familial severe psychiatric history in bipolar disorder and correlation with disease severity and treatment response

Ole Köhler-Forsberg; Louisa G Sylvia; Valerie L Ruberto; Maya Kuperberg; Alec P Shannon; Vicki Fung; Lindsay Overhage; Joseph R Calabrese; Michael Thase; Charles L Bowden; Richard C Shelton; Melvin McInnis; Thilo Deckersbach; Mauricio Tohen; James H Kocsis; Terence A Ketter; Edward S Friedman; Dan V Iosifescu; Susan McElroy; Michael J Ostacher; Andrew A Nierenberg

doi:10.1016/j.jad.2020.03.157

Familial severe psychiatric history in bipolar disorder and correlation with disease severity and treatment response

J Affect Disord. 2020 Aug 1:273:131-137. doi: 10.1016/j.jad.2020.03.157. Epub 2020 May 16.

Authors

Ole Köhler-Forsberg¹, Louisa G Sylvia², Valerie L Ruberto², Maya Kuperberg², Alec P Shannon², Vicki Fung³, Lindsay Overhage⁴, Joseph R Calabrese⁵, Michael Thase⁶, Charles L Bowden⁷, Richard C Shelton⁸, Melvin McInnis⁹, Thilo Deckersbach², Mauricio Tohen¹⁰, James H Kocsis¹¹, Terence A Ketter¹², Edward S Friedman¹³, Dan V Iosifescu¹⁴, Susan McElroy¹⁵, Michael J Ostacher¹⁴, Andrew A Nierenberg²

Affiliations

¹ Psychosis Research Unit, Aarhus University Hospital Psychiatry, Denmark; Department of Clinical Medicin, Aarhus University, Aarhus, Denmark; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: karkoe@rm.dk.
² Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
³ Mongan Institute, Massachusetts General Hospital; Department of Medicine, Harvard Medical School.
⁴ Mongan Institute, Massachusetts General Hospital.
⁵ Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA.
⁶ Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
⁷ Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX, USA.
⁸ Department of Psychiatry, University of Alabama at Birmingham, Birmingham, AL, USA.
⁹ Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
¹⁰ Department of Psychiatry, University of New Mexico Health Science Center, Albuquerque, NM, USA.
¹¹ Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA.
¹² Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
¹³ Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
¹⁴ Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
¹⁵ Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH and Lindner Center of HOPE, Mason, OH, USA.

PMID: 32421593
DOI: 10.1016/j.jad.2020.03.157

Abstract

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.

Keywords: Bipolar disorder; Family history; Genetic; Lithium; Quetiapine; Socioeconomic status; Treatment response.

MeSH terms

Bipolar Disorder* / drug therapy
Bipolar Disorder* / epidemiology
Bipolar Disorder* / genetics
Humans
Lithium
Psychiatric Status Rating Scales
Quetiapine Fumarate
Severity of Illness Index
Suicide, Attempted

Substances

Quetiapine Fumarate
Lithium