title: Familiality of polarity at illness onset in bipolar affective disorder.
abstract: OBJECTIVE
  Bipolar affective disorder is clinically heterogeneous, and clinical features that run in families may help define more homogeneous phenotypes. The authors sought to establish whether polarity at illness onset, which is related to severity and course, is a familial feature of bipolar affective disorder.
  
  
  METHODS
  The authors studied 971 subjects from 507 families ascertained through sibling pairs with bipolar I or schizoaffective bipolar disorder. Self-reported ages at onset of mania and major depression were used to code polarity at onset as manic, major depressive, or both (mania and major depression in the same onset year). Familial clustering was estimated by using mixed-effects regression analysis, and the relationship between polarity at onset and several other clinical features was assessed. As a preliminary test of genetic validity, the authors assessed the impact of polarity at onset on genetic linkage findings previously detected in this sample.
  
  
  RESULTS
  Polarity at onset was significantly familial in this sample. This largely reflected relative pairs concordant for mania at onset, which occurred significantly more frequently than would be expected by chance. Mania at onset substantially increased the genetic linkage signal on chromosome 16p (maximum lod score=4.5) but had no effect on linkage to chromosome 6q. Mania at onset occurred at a later age on average than major depression at onset and was less likely to be complicated by panic attacks or alcoholism.
  
  
  CONCLUSIONS
  Polarity at illness onset is a familial feature of bipolar affective disorder and is associated with important clinical indicators, which may help define more homogeneous subtypes of bipolar affective disorder.
authors.affiliation: Genetic Basis of Mood and Anxiety Disorders, National Institutes of Health, 35 Convent Dr., Rm. 1A202 MSC 3616, Bethesda, MD 20809-3616, USA. kasseml@intra.nimh.nih.gov
authors.forename: Layla
authors.initials: L
authors.lastname: Kassem
authors.forename: Victor
authors.initials: V
authors.lastname: Lopez
authors.forename: Don
authors.initials: D
authors.lastname: Hedeker
authors.forename: Jo
authors.initials: J
authors.lastname: Steele
authors.forename: Peter
authors.initials: P
authors.lastname: Zandi
authors.forename: Francis J
authors.initials: FJ
authors.lastname: McMahon
mesh_terms: D000328:Adult; D017668:Age of Onset; D000437:Alcoholism / Q000175:diagnosis / Q000235:genetics; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D016000:Cluster Analysis; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008126:Lod Score; D008297:Male; D010641:Phenotype; D011618:Psychotic Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D012044:Regression Analysis; D012720:Severity of Illness Index; D035781:Siblings / Q000523:psychology