title: Familial aggregation and heritability of the melancholic and atypical subtypes of depression.
abstract: The heterogeneity of mood disorders has been a challenge to our understanding of their underlying biologic and genetic pathways. This report examines the specificity of the familial aggregation of atypical and melancholic subtypes of depression and their clinical correlates in a large community based family study of affective spectrum disorders.
  
  
  
  The sample includes 457 probands and their directly interviewed adult first degree relatives from the National Institute of Mental Health (NIMH) Family Study of Affective Spectrum Disorder. Depression subtypes were based on best estimate diagnoses using information from semi-structured diagnostic interviews by experienced clinical interviews and multiple family history reports.
  
  
  
  Atypical depression in probands was significantly associated with the atypical subtype of depression in relatives (OR 1.75 [95%CI 1.02-3.02], p=0.04), independent of proband and relative comorbid disorders. Melancholic depression in probands was not associated with melancholic depression in relatives (OR 1.25 [95%CI 0.62-2.55], p=.53). The familial heritability of the atypical subtype was 0.46 (95%CI 0.21-0.71), whereas that of the melancholic subtype was 0.33 (95%CI 0.21-0.45). Melancholic depression was associated with greater severity in terms of treatment, global functioning, suicide attempts, comorbid disorders, and an earlier age at onset of depression.
  
  
  
  The subsample of interviewed relatives necessary to assess specific subtypes of depression reduced the power to detect the specificity of mood disorder subtypes.
  
  
  
  The results indicate that the atypical subtype should be incorporated in future treatment, genetic and other etiologic studies of major depression. Findings further suggest that melancholic subtype may be an indicator of clinical severity of depression.
authors.affiliation: Genetic Epidemiology Research Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: Femke
authors.initials: F
authors.lastname: Lamers
authors.affiliation: Genetic Epidemiology Research Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: Lihong
authors.initials: L
authors.lastname: Cui
authors.affiliation: Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, Camperdown, NSW, Australia.
authors.forename: Ian B
authors.initials: IB
authors.lastname: Hickie
authors.affiliation: Genetic Epidemiology Research Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Roca
authors.affiliation: Experimental Therapeutics and Pathophysiology Research Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Machado-Vieira
authors.affiliation: Experimental Therapeutics and Pathophysiology Research Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Zarate
authors.affiliation: Genetic Epidemiology Research Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA. Electronic address: Kathleen.merikangas@nih.gov.
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Merikangas
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D003863:Depression / Q000235:genetics* / Q000523:psychology; D003866:Depressive Disorder / Q000235:genetics* / Q000523:psychology; D005190:Family / Q000523:psychology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D055815:Young Adult
keywords: Atypical; Epidemiology; Familial aggregation; Major depressive disorder; Melancholic