Genetic Influences on Dual Processing Modes of Reward and Punishment Learning

描述（由申请人提供）：奖励和惩罚过程中的防御是酒精和物质依赖，成瘾和其他精神病理学的理论基石。然而，大多数研究忽略了这样一个事实，即当代认知理论强调两种加工模式：一种是反射模式，其中加工是在意识控制下，主要是前部介导的，另一种是反射模式，不受意识控制，主要是纹状体介导的。此外，详细了解奖励和惩罚双重处理模式的遗传基础对于改善我们的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5-羟色胺基因被假设影响反射性和反射性的奖励和惩罚处理，因此是这个建议的重点。这个项目的总体目标是测试关于多巴胺能和多巴胺能遗传变异对反射性和反射性奖励和惩罚处理的具体假设。我们使用分类学习任务，可以严格定义最佳处理模式（反射或自反），并且研究团队拥有超过20年的经验。拟议的研究还将补充单核苷酸多态性方法与单倍型策略，这将确定这些多巴胺能和多巴胺能基因中的其他变体是否也影响奖励和惩罚处理。我们还将通过测试和统计学控制隐性感染来解释人群分层。 种群亚结构目的1研究多巴胺能和多巴胺能系统的遗传变异与奖励和惩罚处理之间的关联，当最佳表现是由反射系统或反射系统介导的。目的二考察“反射系统”遗传变异对反射最优任务绩效的影响，以及“反射系统”遗传变异对反射最优任务绩效的影响。目的3考察压力对反射性奖惩加工的影响。拟议的研究是第一次尝试使用当代认知框架来描述5-羟色胺，多巴胺和压力对奖励和惩罚的认知处理的交互作用。这种综合性的跨学科研究方法将为未来的翻译工作提供关键的基础，研究这些过程如何在临床疾病中出错。

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.