title: The structure of genetic and environmental risk factors for common psychiatric and substance use disorders in men and women.
abstract: BACKGROUND
  Patterns of comorbidity suggest that the common psychiatric and substance use syndromes may be divisible into 2 broad groups of internalizing and externalizing disorders. We do not know how genetic and environmental risk factors contribute to this pattern of comorbidity or whether the etiologic structure of these groups differ in men and women.
  
  
  METHODS
  Lifetime diagnoses for 10 psychiatric syndromes were obtained at a personal interview in more than 5600 members of male-male and female-female twin pairs ascertained from a population-based registry. Multivariate twin modeling was performed using the program Mx.
  
  
  RESULTS
  We first fit models to the following 7 syndromes: major depression, generalized anxiety disorder, phobia, alcohol dependence, drug abuse/dependence, adult antisocial behavior, and conduct disorder. The full model, which could be constrained to equality in male and female subjects, identified 2 genetic factors. The first had strongest loadings on alcohol dependence, drug abuse/dependence, adult antisocial behavior, and conduct disorder; the second, on major depression, generalized anxiety disorder, and phobia. Alcohol dependence and drug abuse/dependence had substantial disorder-specific genetic risk factors. Shared environmental factors were most pronounced for conduct disorder and adult antisocial behavior. No clear internalizing/externalizing structure was seen for the unique environmental common factors. We then fit models to 5 internalizing syndromes. The full model, which could also be constrained to equality in men and women, revealed one genetic factor loading most heavily on major depression and generalized anxiety disorder and another loading most strongly on animal and situational phobia.
  
  
  CONCLUSIONS
  The underlying structure of the genetic and environmental risk factors for the common psychiatric and drug abuse disorders in men and women is very similar. Genetic risk factors predispose to 2 broad groups of internalizing and externalizing disorders. Within the internalizing disorders, 2 genetic factors are seen that predispose to disorders dominated by anxious-misery and fear. Substance use disorders have disorder-specific genetic risks. The externalizing disorders of conduct disorder and adult antisocial behavior are significantly influenced by the shared environment. The pattern of lifetime comorbidity of common psychiatric and substance use disorders results largely from the effects of genetic risk factors.
authors.affiliation: Virginia Institute for Psychiatry and Behavioral Genetics and the Department of Psychiatry, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0126, USA.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kendler
authors.forename: Carol A
authors.initials: CA
authors.lastname: Prescott
authors.forename: John
authors.initials: J
authors.lastname: Myers
authors.forename: Michael C
authors.initials: MC
authors.lastname: Neale
mesh_terms: D000328:Adult; D015897:Comorbidity; D004200:Diseases in Twins / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D008875:Middle Aged; D008957:Models, Genetic; D015233:Models, Statistical; D015999:Multivariate Analysis; D010641:Phenotype; D015995:Prevalence; D012107:Research Design / Q000592:standards; D012307:Risk Factors; D012737:Sex Factors; D012931:Social Environment; D019966:Substance-Related Disorders / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*