From Phenotype to Mechanism: Mapping the Pathways underlying Risky Choice

描述（由申请人提供）：本申请涉及广泛挑战领域（03）生物标志物、发现和验证，以及特定挑战主题03-MH-101，精神疾病中的生物标志物。我们建议利用来自多个学科的教师之间正在进行的合作，以确定风险决策的个体差异，并绘制这些个体差异的生物标志物。面对风险时的适应不良决定是许多疾病的标志，包括抑郁症，精神分裂症和焦虑症。我们采用了一个机械的研究框架，风险寻求行为反映的不是一个表型，而是风险信息对多个大脑系统的不同影响，每个系统都有潜在的独立遗传贡献。实验积极地整合了尖端的方法--行为经济学、个体差异神经成像、发展认知神经科学和基因组测序--来确定为什么有些人会做出冒险的决定，而另一些人却不会。我们的项目建立在广泛的初步数据，验证的研究方法，合作研究团队和大量的研究基础设施。通过整合这些方法，我们将确定跨临床定义的精神障碍类别的风险决策的生物学预测标记。适应性决策，特别是在风险下，对身心健康至关重要。该项目将确定神经和基因组生物标志物，用于风险决策过程中的个体差异。映射这些过程将提供重要的和新颖的洞察精神健康障碍显着的病理决策。

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.