Abstract
The goal of this study is to investigate the familial transmission of the spectrum of bipolar disorder in a nonclinical sample of probands with a broad range of manifestations of mood disorders. The sample included a total of 447 probands recruited from a clinically enriched community screening and their 2082 adult living and deceased first-degree relatives. A best estimate diagnostic procedure that was based on either direct semistructured interview or structured family history information from multiple informants regarding non-interviewed relatives was employed. Results revealed that there was specificity of familial aggregation of bipolar I (BP I; odds ratio (OR)=8.40; 3.27–20.97; h2=0.83) and major depressive disorder (OR=2.26; 1.58–3.22; h2=0.20), but not BP II. The familial aggregation of BP I was primarily attributable to the familial specificity of manic episodes after adjusting for both proband and relative comorbid anxiety and substance use disorders. There was no significant cross-aggregation between mood disorder subtypes suggesting that the familial transmission of manic and major depressive episodes is independent despite the high magnitude of comorbidity between these mood states. These findings confirm those of earlier studies of the familial aggregation of bipolar disorder and major depression in the first nonclinical sample, and the largest family study of bipolar disorder in the USA using contemporary nonhierarchical diagnostic criteria for mood and anxiety disorders. The results suggest that these major components of bipolar disorder may represent distinct underlying pathways rather than increasingly severe manifestations of a common underlying diathesis. Therefore, dissection of the broad bipolar phenotype in genetic studies could actually generate new findings that could index novel biologic pathways underlying bipolar disorder.
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Acknowledgements
This work was supported by the Intramural Research Program of the National Institute of Mental Health (Z01 MH002804). The authors wish to thank the following individuals who contributed to the development, implementation and analysis of the study: Shelli Avenevoli, PhD, Christina Beccue, PsyD, Francesca Belouad, MA, Marcy Burstein, PhD, Susan Goo, MSN, Jian-ping He, MSc, Suzan Khoromi, MD, Femke Lamers, PhD, Tarannum Lateef, MD, MPH, Nancy CP Low, MD, Andrea Marques, MD, PhD, Vetisha McClair, PhD, Suzanne McGarrity, PhD, Judith Mulvihill, LLD, Kelly Murphy, MSW, Anja Schmitz, PhD, Barbara Usher, PhD, Shreeram Srirangam, MD, April Szilagyi, MSW, Shannon Winters, MSW and Jihui Zhang, MD, PhD. The views and opinions expressed in this article are those of the authors and should not be construed to represent the views of any of the sponsoring organizations, agencies, or US Government.
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Dr Angst has served in advisory or speaking capacities for AstraZeneca, Eli Lilly, Janssen Cilag, and Sanofi-Aventis. The remaining authors declare no conflict of interest.
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Merikangas, K., Cui, L., Heaton, L. et al. Independence of familial transmission of mania and depression: results of the NIMH family study of affective spectrum disorders. Mol Psychiatry 19, 214–219 (2014). https://doi.org/10.1038/mp.2013.116
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DOI: https://doi.org/10.1038/mp.2013.116
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