Previous studies have suggested that certain neuropsychological traits, including socio- emotional information processing, emotion regulation, and behavioral inhibition/impulsivity are associated with aggression. Moreover, converging lines of animal and human lesion evidence have highlighted the role of specific neural substrates such as the amygdala (AMYG), orbital- medial prefrontal cortex (OMPFC), and dorsal anterior cingulate cortex (dACC) in socio- emotional processing and behavioral inhibition (e.g., cognitive control). Therefore, the goal of the present study is to collect multimodal data on specific neuropsychological traits and functional brain reactivity using a sample of twins in order to elucidate the different genetic pathways that may be related to aggressive behavior. Specifically, we propose to measure socio-emotional information processing, emotion regulation, and behavioral inhibition/impulsivity using a series of laboratory-based neuropsychological assessments in a population-based sample of 200 adult twin pairs (100 MZ, 100 DZ) from our PENNTwins Study Program. In addition, we will further conduct BOLD-sensitive functional magnetic resonance imaging (fMRI) studies of Amygdala and OMPFC function during a socio-emotional information processing (SEIP) task and fMRI studies of dACC function during an impulsivity task to assess neurophsyiological patterns of brain response. By investigating the extent to which these characteristics share common genes with aggression and related behaviors, we have the unique opportunity to bridge the gap between phenotype and genotype by examining neuropsychological traits and neurophysiological patterns of brain response as potential mediators of the genetic influence on aggression and related behaviors. Moreover, by applying theoretically-based multivariate models to multimodal assessments of aggression, socio- emotional information processing, and impulsivity, we can also begin to better understand the underlying structure of aggression. Public Health Relevance: Aggression and interpersonal violence are leading worldwide public health problems, both from the viewpoint of the individual who engages in these behaviors and of the people/property that these behaviors target. One of the goals of psychiatric genetic research on aggression is to uncover specific genetic variants that are risk factors for aggression and related disorders. However, it is unlikely that genes code for aggressive behavior directly, but rather influence behavior through indirect mechanisms or pathways. To gain a better understanding of these potential genetic mechanisms, twin studies can be used to identify biologically-based traits that may serve as endophenotpyes for aggression and related behaviors.

R01MH080109

2008-04-16

2014-03-31