Chunk #26 — 3. Insights and Limitations from GWAS of AD — 3.3 The Phenotypic and Genetic Complexity of AD — 3.3.1 Using Comorbidity to Understand Heterogeneity
symptoms and novelty seeking tendencies were more likely to exhibit high levels of alcohol, tobacco, and cannabis DSM-IV dependence symptoms during young adulthood (Palmer et al., 2011). To further complicate matters, AD is one component of the latent Externalizing (EXT) or Behavioral Disinhibition (BD) dimension that represents an inability to controls one’s own impulsive thoughts and actions (Krueger et al., 2002; Young et al., 2000). In addition, one of the largest studies of comorbid psychopathologies (i.e., internalizing and externalizing disorders) by Kendler et al. found separate genetic factors that predispose to internalizing disorders (i.e., major depression, generalized anxiety, and phobia) and externalizing disorders (i.e., AD, other drug dependence, adult antisocial behavior, and conduct disorder; Kendler et al., 2003), suggesting that most of the genetic variance associated with AD is shared with adult antisocial behavior, other drug dependence, and childhood conduct disorder. Consequently, it is important to consider whether genetic studies of AD, truly indicate susceptibility factors specifically related to AD.
