title: Evidence for multiple genetic factors underlying DSM-IV criteria for major depression.
abstract: OBJECTIVE
  We do not know whether the clinical criteria for major depression (MD) reflect a single or multiple dimensions of genetic risk.
  
  
  OBJECTIVE
  To determine the structure of genetic and environmental risk factors for the 9 DSM-IV symptomatic MD criteria.
  
  
  METHODS
  Population-based twin registry.
  
  
  METHODS
  Virginia.
  
  
  METHODS
  Seven thousand five hundred members of adult twin pairs from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders.
  
  
  METHODS
  Symptoms of lifetime MD as assessed at personal interview.
  
  
  RESULTS
  The best-fit twin model was multidimensional, requiring 3 genetic, 1 common environmental and 3 unique environmental common factors, and criterion-specific unique environmental factors. The first genetic factor was characterized by high loadings on cognitive and psychomotor depressive symptoms. The second and third genetic factors had strong loadings for mood and neurovegetative depressive symptoms, respectively. Genetic factor scores derived from these 3 factors differentially predicted patterns of comorbidity, other historical/clinical features of MD, and demographic variables. These results suggested that the first genetic factor reflected a general liability to internalizing disorders, while the third genetic factor was more specific for melancholic MD. The 3 unique environmental common factors reflected, respectively, global depressive, core mood, and cognitive depressive symptoms.
  
  
  CONCLUSIONS
  The DSM-IV syndrome of MD does not reflect a single dimension of genetic liability. Rather, these criteria reflect 3 underlying dimensions that index genetic risk for cognitive/psychomotor, mood, and neurovegetative symptoms. While in need of replication, these results, validated by predictions using estimated genetic factor scores, have implications for gene-finding efforts for MD.
authors.affiliation: Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond 23298, USA. kendler@vcu.edu
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kendler
authors.forename: Steven H
authors.initials: SH
authors.lastname: Aggen
authors.forename: Michael C
authors.initials: MC
authors.lastname: Neale
mesh_terms: D000328:Adult; D003863:Depression / Q000235:genetics / Q000523:psychology; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004200:Diseases in Twins / Q000235:genetics / Q000523:psychology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007406:Interview, Psychological; D008297:Male; D015999:Multivariate Analysis; D012307:Risk Factors; D014429:Twins, Dizygotic / Q000235:genetics / Q000523:psychology; D014430:Twins, Monozygotic / Q000235:genetics / Q000523:psychology