title: The temporal relationship of the onsets of alcohol dependence and major depression: using a genetically informative study design.
abstract: BACKGROUND
  Although alcohol dependence (AD) and major depression (MD) are highly co-morbid, their causal relationship is unclear. In this longitudinal study, we used a genetically informative population-based twin sample to examine the age-at-onset distributions and the temporal relationship of AD and MD.
  
  
  METHODS
  Our sample included 7477 twins, whose diagnoses of AD and MD and age-at-onset information were obtained from structured interviews. Individual-level survival analyses were conducted based on 2603 monozygotic (MZ) twins, and co-twin diagnosis was included in models as an index of familiar liability to AD and MD.
  
  
  RESULTS
  The age-at-onset distributions of AD and MD differed substantially. Most onsets of AD were in young adulthood, whereas MD had a flatter distribution across age. Most subjects, especially women, had an onset of MD preceding AD. Prior MD significantly affected risk for developing AD, and this risk decreased over time. By contrast, preceding AD had negligible effects on the risk for future MD. Familial risk was transmitted within disorders but there was little evidence of additional familial liability shared across disorders.
  
  
  CONCLUSIONS
  Risk for developing AD was substantially increased by a prior episode of MD. The association was only partially accounted for by familial factors, providing support for a direct causal effect such as self-medication. The etiologic path from AD to MD was insignificant.
authors.affiliation: Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298-0126, USA. pkuo@vcu.edu
authors.forename: Po-Hsiu
authors.initials: PH
authors.lastname: Kuo
authors.forename: Charles O
authors.initials: CO
authors.lastname: Gardner
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kendler
authors.forename: Carol A
authors.initials: CA
authors.lastname: Prescott
mesh_terms: D000328:Adult; D000367:Age Factors; D000437:Alcoholism / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D015897:Comorbidity; D003865:Major Depressive Disorder / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D004200:Diseases in Twins / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012737:Sex Factors; D013223:Statistics as Topic; D014429:Twins, Dizygotic / Q000235:genetics / Q000523:psychology; D014430:Twins, Monozygotic / Q000235:genetics / Q000523:psychology