title: Major depression and coronary artery disease in the Swedish twin registry: phenotypic, genetic, and environmental sources of comorbidity.
abstract: BACKGROUND
  Major depresssion (MD) and coronary artery disease (CAD) frequently co-occur. The mechanisms of comorbidity are uncertain.
  
  
  OBJECTIVE
  To clarify sources of MD-CAD comorbidity.
  
  
  METHODS
  Major depression was assessed at the time of the personal interview, and CAD from hospital discharge records and death certificates.
  
  
  METHODS
  Swedish population-based twin registry.
  
  
  METHODS
  The study included 30 374 twins with a mean age of 57 years. Main Outcome Measure Modified DSM-IV diagnosis of MD or diagnosis of CAD.
  
  
  RESULTS
  Lifetime association between MD and CAD was modest (odds ratio, approximately 1.3). In time-dependent Cox analyses, onset of CAD produced concurrent and ongoing hazard ratios for MD of 2.83 and 1.75. These risks increased if the diagnosis of CAD was restricted to myocardial infarction. Onset of MD increased the concurrent and ongoing hazard ratios for CAD to 2.53 and 1.17. The ongoing CAD risk was strongly associated with depressive severity and recurrence. Twin models showed that the modest comorbidity between MD and CAD in women arose primarily from shared genetic effects, although the genetic correlation was small (+0.16). In men, the source of comorbidity was moderated by age, being environmental in older members and largely genetic in younger members of the sample.
  
  
  CONCLUSIONS
  Although the MD-CAD relationship across the lifespan is modest, time-dependent models reveal stronger associations. The sustained effect of CAD onset on MD risk is much stronger than vice versa. The effect of MD on CAD is largely acute, and the longer-term effects are apparently mediated via depressive recurrence. When examined separately, in men, environmental effects, which are often acute, play a large role in MD-CAD comorbidity, whereas in women, chronic effects, which are in part genetic, are more important. In men, genetic sources of MD-CAD comorbidity are more important in younger members of the sample.
authors: Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298-0126, USA. kendler@vcu.edu
authors: Kenneth S
authors: KS
authors: Kendler
authors: Charles O
authors: CO
authors: Gardner
authors: Amy
authors: A
authors: Fiske
authors: Margaret
authors: M
authors: Gatz
mesh_terms: D000368:Aged; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000235:genetics*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004200:Diseases in Twins / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D010641:Phenotype; D016016:Proportional Hazards Models; D011569:Psychiatric Status Rating Scales; D012042:Registries / Q000706:statistics & numerical data; D012307:Risk Factors; D012737:Sex Factors; D012931:Social Environment; D013548:Sweden / Q000453:epidemiology; D014427:Twins