The promise of measuring dimensions of personality disorder symptoms leads to the possibility of linking those measures to physiological substrates. As succinctly stated by Jang and Vernon (2001): "The definition of the phenotype remains the most important prerequisite for successful genetic studies" (p. 177). In other words, investigators can most easily link protein expression mechanisms to phenotypes that are internally coherent, distinct from other phenotypes, and stable across measurement attempts. Because some personality traits show desirable psychometric qualities of validity and reliability and describe key features of personality disorders, they may provide ideal "endophenotypes" for linkage to genetic and intermediate physiological mechanisms (Jang and Vernon, 2001). Investigations of the relationship between genetic polymorphisms and personality traits provide fertile ground for inquiry. For instance, mice genetically engineered to lack serotonin 1a receptors show increased anxious behavior, and this anxious behavior can be normalized by "knocking in" forebrain serotonin receptors through genetic induction in adulthood (Gross et al., 2002). These findings provide an exciting parallel to the recently observed association between a genetic polymorphism that regulates serotonin function and neuroticism (a personality trait that indexes the chronic experience of anxiety) in humans (Lesch et al., 1996).
Indeed, as in the case of "normal" personality traits, a large twin study has revealed substantial heritability of traits that index personality disorder symptoms (Jang et al., 2000). This heritable component implies a model in which gene expression leads to protein expression, which alters neurophysiological function, which manifests in behavioral tendencies, which over time manifest as a trait, which may confer vulnerability to an eventual personality disorder. Along with inheritance, environmental influences surely also influence gene expression. Either way, the simple causal model outlined above suggests that the physiological correlates of personality disorder symptoms should be more closely associated with behavioral traits than with specific diagnoses. We turn now to review evidence for physiological correlates of personality disorder symptoms.
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