title: Age-at-onset in bipolar-I disorder: mixture analysis of 1369 cases identifies three distinct clinical sub-groups.
abstract: BACKGROUND
  To assess whether bipolar disorder type I segregates into three clinically distinct sub-groups defined by age-at-onset.
  
  
  METHODS
  Clinical data were available on 1369 individuals with DSM-IV bipolar I disorder. Mixture analysis was performed on the age-at-onset (AAO) data to determine whether they were composed of more than one normal distribution. Individuals were allocated to groups according to the results of the mixture analysis. Categorical logistic regression was then used to investigate relationships between AAO and nine clinical characteristics.
  
  
  RESULTS
  The distribution of AAOs in our sample comprised a mixture of three normal distributions with means of 18.7 (SD=3.7), 28.3 (SD=5.5) and 43.3 (SD=9.1) years, with relative proportions of 0.47, 0.39 and 0.14 respectively. Individuals were allocated into three groups dependent on their AAO: < or = 22; 25-37; and > or = 40 years, producing a sample of 1225 individuals (144 with borderline values were excluded). Eight out of the nine clinical characteristics showed evidence for a statistical association with AAO group.
  
  
  CONCLUSIONS
  Systematic and non-systematic recruitment of participants. Some data relied on retrospective recall.
  
  
  CONCLUSIONS
  Our results provide further robust evidence to suggest that the AAO distribution of individuals affected with bipolar disorder is composed of three normal distributions. Substantial clinical heterogeneity between the three AAO groups may reflect genetic heterogeneity within bipolar I disorder. Future genetic studies should consider AAO grouping as potential sub-phenotypes.
authors.affiliation: Biostatistics and Bioinformatics Unit, Wales School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, United Kingdom. HamshereML@cardiff.ac.uk
authors.forename: Marian L
authors.initials: ML
authors.lastname: Hamshere
authors.forename: Katherine
authors.initials: K
authors.lastname: Gordon-Smith
authors.forename: Liz
authors.initials: L
authors.lastname: Forty
authors.forename: Lisa
authors.initials: L
authors.lastname: Jones
authors.forename: Sian
authors.initials: S
authors.lastname: Caesar
authors.forename: Christine
authors.initials: C
authors.lastname: Fraser
authors.forename: Sally
authors.initials: S
authors.lastname: Hyde
authors.forename: John
authors.initials: J
authors.lastname: Tredget
authors.forename: George
authors.initials: G
authors.lastname: Kirov
authors.forename: Ian
authors.initials: I
authors.lastname: Jones
authors.forename: Nick
authors.initials: N
authors.lastname: Craddock
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Smith
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000367:Age Factors; D017668:Age of Onset; D001714:Bipolar Disorder / Q000145:classification / Q000175:diagnosis*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016011:Normal Distribution; D011569:Psychiatric Status Rating Scales; D011594:Psychometrics; D055815:Young Adult