title: Genetic risk of suicidal behavior in bipolar spectrum disorder: analysis of 737 pedigrees.
abstract: OBJECTIVE
  Suicide is a significant cause of mortality in patients with major affective disorders (MAD), and suicidal behavior and MAD co-aggregate in families. However, the transmission of suicidal behavior is partially independent from that of MAD. We analyzed the lifetime prevalence of completed and attempted suicides in a large sample of families with bipolar disorder (BD), its relation to family history of MAD and BD, and the contribution of clinical and treatment factors to the risk of suicidal behavior.
  
  
  METHODS
  We studied 737 families of probands with MAD with 4919 first-degree relatives (818 affected, 3948 unaffected, and 153 subjects with no information available). Lifetime psychiatric diagnoses and suicidal behavior in first-degree relatives were assessed using semi-structured interviews, family history methods, and reviews of clinical records. Cox proportional hazard and logistic regression models were used to investigate the role of clinical covariates in the risk of suicidal behavior, and in the prevalence of MAD and BD.
  
  
  RESULTS
  The estimated lifetime prevalence of suicidal behavior (attempted and completed suicides) in 737 probands was 38.4 ± 3.0%. Lithium treatment decreased suicide risk in probands (p = 0.007). In first-degree relatives, a family history of suicidal behavior contributed significantly to the joint risk of MAD and suicidal behavior (p = 0.0006).
  
  
  CONCLUSIONS
  The liability to suicidal behavior is influenced by genetic factors (particularly family history of suicidal behavior and MAD). Even in the presence of high genetic risk for suicidal behavior, lithium treatment decreases suicide rates significantly.
authors.affiliation: Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.
authors.forename: Mirko
authors.initials: M
authors.lastname: Manchia
authors.forename: Tomas
authors.initials: T
authors.lastname: Hajek
authors.forename: Claire
authors.initials: C
authors.lastname: O'Donovan
authors.forename: Valeria
authors.initials: V
authors.lastname: Deiana
authors.forename: Caterina
authors.initials: C
authors.lastname: Chillotti
authors.forename: Martina
authors.initials: M
authors.lastname: Ruzickova
authors.forename: Maria
authors.initials: M
authors.lastname: Del Zompo
authors.forename: Martin
authors.initials: M
authors.lastname: Alda
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology*; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D012307:Risk Factors; D013405:Suicide / Q000523:psychology*
keywords: bipolar disorder; family study; genetic risk; lithium; mood disorder; suicidal behavior; treatment response