title: Comparison of depressive episodes in bipolar disorder and in major depressive disorder within bipolar disorder pedigrees.
abstract: BACKGROUND
  Although genetic epidemiological studies have confirmed increased rates of major depressive disorder among the relatives of people with bipolar affective disorder, no report has compared the clinical characteristics of depression between these two groups.
  
  
  OBJECTIVE
  To compare clinical features of depressive episodes across participants with major depressive disorder and bipolar disorder from within bipolar disorder pedigrees, and assess the utility of a recently proposed probabilistic approach to distinguishing bipolar from unipolar depression. A secondary aim was to identify subgroups within the relatives with major depression potentially indicative of 'genetic' and 'sporadic' subgroups.
  
  
  METHODS
  Patients with bipolar disorder types 1 and 2 (n = 246) and patients with major depressive disorder from bipolar pedigrees (n = 120) were assessed using the Diagnostic Interview for Genetic Studies. Logistic regression was used to identify distinguishing clinical features and assess the utility of the probabilistic approach. Hierarchical cluster analysis was used to identify subgroups within the major depressive disorder sample.
  
  
  RESULTS
  Bipolar depression was characterised by significantly higher rates of psychomotor retardation, difficulty thinking, early morning awakening, morning worsening and psychotic features. Depending on the threshold employed, the probabilistic approach yielded a positive predictive value ranging from 74% to 82%. Two clusters within the major depressive disorder sample were found, one of which demonstrated features characteristic of bipolar depression, suggesting a possible 'genetic' subgroup.
  
  
  CONCLUSIONS
  A number of previously identified clinical differences between unipolar and bipolar depression were confirmed among participants from within bipolar disorder pedigrees. Preliminary validation of the probabilistic approach in differentiating between unipolar and bipolar depression is consistent with dimensional distinctions between the two disorders and offers clinical utility in identifying patients who may warrant further assessment for bipolarity. The major depressive disorder clusters potentially reflect genetic and sporadic subgroups which, if replicated independently, might enable an improved phenotypic definition of underlying bipolarity in genetic analyses.
authors.affiliation: UNSW School of Psychiatry, Prince of Wales Hospital, Randwick, Australia. phil.mitchell@unsw.edu.au
authors.forename: Philip B
authors.initials: PB
authors.lastname: Mitchell
authors.forename: Andrew
authors.initials: A
authors.lastname: Frankland
authors.forename: Dusan
authors.initials: D
authors.lastname: Hadzi-Pavlovic
authors.forename: Gloria
authors.initials: G
authors.lastname: Roberts
authors.forename: Justine
authors.initials: J
authors.lastname: Corry
authors.forename: Adam
authors.initials: A
authors.lastname: Wright
authors.forename: Colleen K
authors.initials: CK
authors.lastname: Loo
authors.forename: Michael
authors.initials: M
authors.lastname: Breakspear
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D016000:Cluster Analysis; D003865:Major Depressive Disorder / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D003937:Diagnosis, Differential; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007406:Interview, Psychological; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D013406:Suicide, Attempted / Q000706:statistics & numerical data