Genetic Influences on Dual Processing Modes of Reward and Punishment Learning

描述（由申请人提供）：奖励和惩罚处理的缺陷是酒精和物质依赖、成瘾和其他精神病理的理论基础。然而，大多数研究忽略了一个事实，即当代认知理论强调两种加工模式：一种是反射模式，加工受意识控制，主要由额叶介导；另一种是反射模式，不受意识控制，主要由纹状体介导。此外，详细了解奖惩双重处理模式的遗传基础对于改善成瘾和精神病理学理论以及专注于开发干预措施的翻译工作至关重要。多巴胺和血清素基因被假设影响反射性和反思性奖惩处理，因此是本建议的重点。该项目的总体目标是测试关于多巴胺能和血清素能基因变异对反射性和反射性奖惩处理的特定假设。我们使用分类学习任务，可以严格定义最佳处理模式（反射或反射），并且研究团队拥有超过20年的经验。拟议的研究还将用单倍型策略补充单核苷酸多态性方法，这将确定这些多巴胺能和血清素能基因的其他变异是否也影响奖惩处理。我们还将通过测试和统计控制隐匿性来解释人口分层

DESCRIPTION (provided by applicant): Deficiencies in reward and punishment processing are theoretical cornerstones of alcohol and substance dependence, addiction, and other psychopathology. However, most research ignores the fact that contemporary cognitive theory emphasizes two processing modes: a reflective mode where processing is under conscious control and predominantly frontally-mediated, and a reflexive mode that is not under conscious control and is predominantly striatally-mediated. In addition, a detailed understanding of the genetic underpinnings of dual processing modes of reward and punishment is critical to improving our theories of addiction and psychopathology and to translational work focused on developing interventions. Dopamine and serotonin genes are hypothesized to affect reflexive and reflective reward and punishment processing and are therefore the focus of this proposal. The overall goal of this project is to test specific hypotheses regarding dopaminergic and serotonergic genetic variation on reflexive and reflective reward and punishment processing. We use classification learning tasks for which the optimal mode of processing (reflective or reflexive) can be defined rigorously and for which the research team has over 20 years of experience. The proposed studies will also complement a single nucleotide polymorphism approach with a haplotype strategy, which will determine whether additional variants in these dopaminergic and serotonergic genes also influence reward and punishment processing. We will also account for population stratification by testing and statistically controlling for occult population substructure. Aim 1 examines associations between genetic variation in dopaminergic and serotonergic systems with reward and punishment processing when optimal performance is mediated by the reflexive system or by the reflective system. Aim 2 examines the effects of "reflexive system" genetic variation on reflective-optimal task performance, and "reflective system" genetic variation on reflexive-optimal task performance. Aim 3 examines the influence of stress on reflexive reward and punishment processing. The proposed studies are the first to attempt to characterize the interactive effects of serotonin, dopamine and stress on cognitive processing of rewards and punishment using contemporary cognitive frameworks. This integrative, interdisciplinary research approach will provide the critical foundation needed for future translational work that examines how these processes go awry in clinical disorders. PUBLIC HEALTH RELEVANCE: Deficiencies in reward and punishment processing are theoretical cornerstones of alcohol and substance dependence, addiction, and other psychopathology, yet little is known about these are affected by task goals, genetic variation or stress. The overall goal of the proposed research is to provide a detailed understanding of the genetic underpinnings of dual processing modes of reward and punishment which is critical to improving our theories of addiction and psychopathology and to translational work focused on developing interventions.