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Mol Psychiatry. 2014 Feb;19(2):214-9. doi: 10.1038/mp.2013.116. Epub 2013 Oct 15.

Independence of familial transmission of mania and depression: results of the NIMH family study of affective spectrum disorders.

Author information

Genetic Epidemiology Research Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
Computational Biology Core, Laboratory of Neurogenetics, National Institute of Aging, Bethesda, MD, USA.
Unit on Statistical Genomics, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
Experimental Therapeutics and Pathophysiology Research Branch, National Institute of Mental Health, Bethesda, MD, USA.
Department of Psychiatry, Zurich University Hospital, Zurich, Switzerland.

Erratum in

  • Mol Psychiatry. 2014 Feb;19(2):272. Yao-Shugart, Y [corrected to Shugart, Y Y].


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.

[Indexed for MEDLINE]

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