From Phenotype to Mechanism: Mapping the Pathways underlying Risky Choice

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DESCRIPTION (provided by applicant): This application addresses Broad Challenge Area (03) Biomarker, Discovery and Validation, with specific Challenge Topic, 03-MH-101, Biomarkers in Mental Disorders. We propose to leverage an ongoing collaboration among faculty from several disciplines to identify individual differences in risky decision making and to map biomarkers of those individual differences. Maladaptive decisions when faced with risk are hallmarks of many disorders, including depression, schizophrenia, and anxiety. We adopt a mechanistic research framework that risk-seeking behavior reflects, not one phenotype, but distinct effects of risk information upon multiple brain systems, each with potentially independent genetic contributions. Experiments aggressively integrate cutting- edge methods -- behavioral economics, individual difference neuroimaging, developmental cognitive neuroscience, and genome sequencing -- to determine why some people make risky decisions and others do not. Our project builds upon extensive preliminary data, validated research methods, a collaborative research team, and a substantial research infrastructure. By integrating these methods, we will identify biologically predictive markers of risky decision making that cut across clinically-defined categories of mental disorders. Adaptive decision making, especially under risk, is critical for mental and physical health. This project will identify biomarkers, both neural and genomic, for individual differences in the processes that underlie risky decision making. Mapping these processes will provide important and novel insight into mental health disorders notable for pathologies of decision making.