Neurocognitive Abnormalities in Stimulant Abuse among High-Risk Women

Project Abstract There continues to be great interest and public/health/relevance with regard to understanding the neurobiological systems that underlie the comorbidity of substance use disorders and other psychiatric conditions. In a previous R01 award, we focused our efforts upon characterizing the neural circuitry underlying moral decision making in incarcerated men with varying levels of two frequently co-occurring conditions: stimulant abuse and psychopathy. Here we propose to extend this work to incarcerated women, examine longitudinal outcomes, and apply stateof-the-art network analyses for predictive models. Studies published by our research team have demonstrated sex differences in the degree and expression of psychopathic traits, patterns of stimulant abuse, and moral decision-making. However, the neural circuitry that underlies these sex differences is not well understood. We have also identified substantial sex differences in regional gray matter volume and density in our extant samples. Collectively, sex differences in pathophysiology could have significant implications for treatment strategies and differential biomarkers of treatment prediction and outcome in men and women. We will implement the research strategy with a large incarcerated population by deploying a unique mobile MRI scanner to the regional women’s prison. Participants will be stratified by their level of lifetime stimulant (cocaine, amphetamine) use severity and psychopathic traits (high, medium, low) and will undergo anatomical and functional MRI scanning while completing multi-modal (i.e., linguistic and picture) decision-making tasks. We will also examine functional network and dynamic network connectivity in women using a new multiband EPI pulse sequence, and collect longitudinal outcomes after release to the community and test behavioral and neuropredictive models of relapse and future antisocial behavior. This work is expected to generate a large, robust dataset that characterizes the overlapping and unique aspects of neural circuitry underlying stimulant use and psychopathy in females. The proposed research is in line with recent priorities emphasized by NIDA for projects aimed at examining gender differences, and effects specific to females, to improve our understanding of the nature and etiology of drug abuse.