7 Multivariate analyses, which comprise models where several phenotypes are included
and different structures of the latent factors can be specified,20 can be used to estimate to what extent genetic and environmental risk factors are specific to a given PD or shared in common with other PDs or axis I disorders, and thus to investigate sources of comorbididity.49,50 By including measures of the same phenotypes on different points in time, they can also be used to determine if genetic effects differ over time in a developmental perspective. DSM-IV personality disorders Cluster A PDs have been found to aggregate in families of probands with Inhibitors,research,lifescience,medical schizophrenia (see below). Familial coaggregation has also been found for borderline PD and antisocial PD39 and for borderline PD and all the other cluster B PDs,51 as well as for the DSM-III cluster C PDs.44 A unfortunately population-based Inhibitors,research,lifescience,medical twin study including all PDs within
cluster B indicated that borderline PD and antisocial PD appeared to share genetic risk factors above and beyond those shared in Inhibitors,research,lifescience,medical common with the other cluster B disorders,43 and a twin study of cluster C PDs suggested that genetic factors influencing obsessive-compulsive PD appeared to be relative specific to this disorder.45 Kendler et al, in the only population-based multivariate twin study including all 10 DSM-IV PDs that has been published,52 found that the best-fitting model included three genetic and three environmental factors in addition to disorder-specific factors. The structure of the genetic factors is shown in
Figure 1. The first genetic factor (AC1) had high Tipifarnib myeloid loadings on PDs from all 3 clusters Inhibitors,research,lifescience,medical including paranoid, histrionic, borderline, narcissistic, dependent, and obsessive-compulsive PD. This factor probably reflects a broad vulnerability to PD pathology and/or negative emotionality, and is related to genetic liability to the normal personality trait neuroticism. The second genetic factor (AC2)was quite specific with substantial loadings only on borderline and antisocial PD. This is Inhibitors,research,lifescience,medical consistent with the results from the abovementioned family studies,39 and suggests genetic liability to a broad phenotype for impulsive/aggressive GSK-3 behavior. The third factor identified (AC3) had high loadings only on schizoid and avoidant PD. This can be interpreted in several ways. It might in part reflect genetic risk for schizophrenia spectrum pathology (see below). From the perspective of the five-factor model of normal personality it reflects genetic liability for introversion.53 Finally, it is noteworthy that obsessive-compulsive PD had the highest disorder-specific genetic loading, which parallels prior findings that this PD shares little genetic and environmental liability with the other cluster C PDs. Figure 1 Genetic parameter estimates from best fitting model for ten DSM-IV personality disorders.