Brain Structural Variations as Potential Endophenotypes for Psychopathic Traits

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DESCRIPTION (provided by applicant): Psychopathy is a clinical condition that affects approximately 2% of the general population, and ~25% of criminal offenders, and reflects a failure in normal social interaction and morality. Despite increasing evidence showing brain structural abnormalities in adult psychopaths, the lack of neuroimaging findings for psychopathic traits among adolescents has prevented further understanding in the etiology of such complex personality traits. The candidate's immediate career goal is to develop expertise in structural brain imaging and quantitative genetic analysis in order to identify which brain morphological characteristics pose as candidate endophenotypes for psychopathic traits. Understanding the genetic contributions of brain morphological variations in relation to psychopathic traits in adolescents will build the necessary foundation for a rigorous examination of the genetic predispositions to psychopathic traits and make possible the candidate's long-term career goal of developing independent large-scale projects using neuroimaging phenotypes and multivariate methods to investigate the genetic contributions of psychopathy and related disorders from childhood through adulthood. Towards this end, using the existing neuroimaging, clinical, and behavioral data of 80 adolescent twins collected from a larger longitudinal twin project, we propose to; 1) use several sophisticated neuroimaging analysis methods applied to structural magnetic resonance imaging (sMRI) and diffusion tensor imaging (DTI) data to characterize structural brain phenotypes and examine their association with psychopathic traits (identified using the Childhood Psychopathy Scale and the Antisocial Process Screening Device); 2) use structural equation modeling to estimate the relative contributions of genetic and non-genetic factors toward morphological variations; and to 3) collect new imaging and clinical data on an additional 160 adolescent twins from the larger twin project in the R00 phase to determine the genetic overlap between morphological variations and psychopathic traits. The candidate's formal training will take advantage of the rich genetic expertise and neuroimaging resources at UCLA and USC and will include eight didactic courses, two intensive workshops and regular weekly seminars designed to augment the candidate's prior experience in image analysis methods, foster new knowledge in behavioral genetic analysis and child psychopathy, and promote skills for conducting an independent longitudinal twin project. Additionally, the candidate will receive training for the preparation for academic advancement to enhance a smooth transitioning into a tenure-track, full-time assistant professorship for the proposed R00 phase research. PUBLIC HEALTH RELEVANCE: Psychopathic traits in children and adolescents have been linked to several adult psychiatric disorders, however extremely little is known regarding the neural basis of psychopathic traits in adolescents. By identifying structural correlates of psychopathic traits and examining the heritability for morphological characteristics using an adolescent twin sample, we can determine the candidate endophenotypes for psychopathic traits. This proposed study thus has great potential for identifying etiologically relevant precursors of psychopathy, which in turn would be crucial for developing new hypothesis, treatments, and preventative interventions.