Cunningham, Kathryn (P) | Anastasio, Noelle | Garcia, Maria | Gilbertson, Scott | Harvey, Edythe | Hommel, Jonathan | Jordan, Marcy | Kasper, James | Kuo, Yong-fang | Le, Donna | Moeller, F. Gerald | Nowakowski, Sara | Price, Amanda | Scott, Lauren | Sowers, Lawrence | Temple, Jeff | Thomas, Christopher | Wooten, Kevin | Zhou, Jia
Summary: The overarching goal of this MTT is to develop the best practices of translational research and employ these to discover new biomarkers and therapeutic approaches to the addictions and impulse control disorders. Building on our core strengths in cellular and animal models, clinical science, and chemistry, this MTT is addressing the fundamental gap between the genes, biology and impulsivity which underlies a spectrum of health maladies. Impulsivity or “action without reflection” is an endophenotype for the addictions, aggression/violence and obesity/binge eating disorders, conditions that together account for an incredible portion of the chronic disease burden in the U.S.
We are building on our prior studies that serotonin (5-HT) transmission, particularly through its cognate 5-HT2A receptor (5-HT2AR) and 5-HT2CR proteins, plays a key role in inherent levels of impulsivity, and explore the specific linkage between the biology of the 5-HT2AR/5-HT2CR systems and impulsivity in humans. Our overarching hypothesis is that high tonic/constitutive 5-HT2AR function and low tonic/constitutive 5-HT2CR function are drivers of high impulsivity. To test this hypothesis, we will develop a human subjects laboratory (Specific Aim 1) at UTMB to clinically (Barratt Impulsivity Scale; BIS-11) and experimentally analyze impulsivity in three behavioral tasks (Go/No-Go task, reversal learning task, reward-word Stroop task). We will recruit healthy human subjects (18-55 yr), collect blood samples and evaluate clinical and behavioral laboratory measures of impulsivity as well as subject history information on addiction, violence and eating behavior.