A GENETICALLY INFORMED STUDY OF ACUTE THREAT ENDOPHENOTYPES FOR CALLOUS-UNEMOTIONAL TRAITS

Introduction. Callous-unemotional (CU) traits predict socially debilitating outcomes including Antisocial Personality Disorder and violent crime in adulthood. Despite significant research, the etiology of CU traits is not well understood. This dissertation incorporates genetic, physiological, neuroanatomical, and self-report measures to investigate the etiology of CU traits. Specifically, this project focuses on measures previously found to associate with impaired fear-processing observed in individuals high on CU. Brain morphometry for paralimbic regions of interest (ROIs) and electromyographic facial eyeblink reflex to startle and fear-potentiated startle probes were investigated as potential endophenotypes for CU traits. Methods. Two genetically informative (ages 9-20) twin samples (N=1696 individuals; 848 twin pairs) were used to estimate the changing heritable and environmental influences on CU over the age range of 9-20 using age-moderated biometric structural equation modeling (SEM). To determine potential endophenotypes, shared genetic variance with CU was examined for baseline and fear-potentiated startle reflex and morphometric measures of brain ROIs. Results. The heritability of CU increases over the ages of 9-20, from approximately 34% at age 9 to 47% at age 20. Therefore, environmental mechanisms for CU are most influential at younger ages. Although there were no significant associations after correction for multiple testing, there was some evidence to suggest potential positive associations between CU traits and baseline and fear-potentiated startle in younger (9-14) females. There was also evidence suggesting potential negative associations between CU traits and right anterior cingulate cortex thickness as well as right posterior cingulate cortex thickness in females only. There was no genetic covariance between CU and any of the examined physiological or neuroanatomical phenotypes. Discussion. These results suggest that middle childhood may be the most salient time for environmental interventions associated with preventing or ameliorating CU traits. Furthermore, these results suggest that the cingulate cortex may play a role in the development of CU traits, possibly in females specifically. The cingulate cortex may influence CU traits through its roles in emotional processing, learning, and memory. Larger samples will likely be needed to determine the genetic relationship between CU traits and the structural development of the cingulate cortex