title: Independence of familial transmission of mania and depression: results of the NIMH family study of affective spectrum disorders.
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.
authors.affiliation: Genetic Epidemiology Research Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Merikangas
authors.affiliation: Genetic Epidemiology Research Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: L
authors.initials: L
authors.lastname: Cui
authors.affiliation: Genetic Epidemiology Research Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: L
authors.initials: L
authors.lastname: Heaton
authors.affiliation: Genetic Epidemiology Research Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: E
authors.initials: E
authors.lastname: Nakamura
authors.affiliation: Genetic Epidemiology Research Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: C
authors.initials: C
authors.lastname: Roca
authors.affiliation: Computational Biology Core, Laboratory of Neurogenetics, National Institute of Aging, Bethesda, MD, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ding
authors.affiliation: Unit on Statistical Genomics, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: H
authors.initials: H
authors.lastname: Qin
authors.affiliation: Unit on Statistical Genomics, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: W
authors.initials: W
authors.lastname: Guo
authors.forename: Y Y
authors.initials: YY
authors.lastname: Shugart
authors.affiliation: Unit on Statistical Genomics, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Yao-Shugart
authors.affiliation: Experimental Therapeutics and Pathophysiology Research Branch, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: C
authors.initials: C
authors.lastname: Zarate
authors.affiliation: Department of Psychiatry, Zurich University Hospital, Zurich, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Angst
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001007:Anxiety / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D001714:Bipolar Disorder / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D003863:Depression / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D003865:Major Depressive Disorder / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005192:Family Health; D005260:Female; D006801:Humans; D007406:Interview, Psychological; D008297:Male; D008875:Middle Aged; D008960:Models, Psychological; D016017:Odds Ratio; D015995:Prevalence; D019966:Substance-Related Disorders / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D055815:Young Adult