Genetic Influences on Dual Processing Modes of Reward and Punishment Learning

描述(由申请人提供)：奖惩过程中的缺陷是酒精和物质依赖、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：一种是有意识控制的、以前向调节为主的反射加工模式，另一种是不受意识控制、以纹状体调节为主的反射加工模式。此外，详细了解奖惩双重加工模式的遗传基础，对于改进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奖惩过程，因此是本提案的重点。这个项目的总体目标是测试关于多巴胺和5-羟色胺能在反射性和反射性奖惩加工过程中的遗传变异的具体假设。我们使用分类学习任务，其最佳处理模式(反思性或反身性)可以被严格定义，并且研究团队对其有20多年的经验。拟议的研究还将用单倍型策略来补充单核苷酸多态方法，该策略将确定这些多巴胺和5-羟色胺能基因的额外变异是否也影响奖惩过程。我们还将通过测试和统计控制隐蔽性来说明人口分层 人口子结构。目的1研究多巴胺能和5-羟色胺能系统的遗传变异与奖惩加工之间的关系，当最佳表现由反射系统或反射系统调节时。目的2考察“反身性系统”遗传变异对反思性最优任务绩效的影响，以及“反身性系统”遗传变异对反身性最优任务绩效的影响。目的3考察压力对条件性奖惩加工的影响。这项拟议的研究首次尝试利用当代认知框架来表征5-羟色胺、多巴胺和压力对奖惩认知加工的交互影响。这种综合的、跨学科的研究方法将为未来的翻译工作提供必要的关键基础，该工作将检查这些过程在临床疾病中是如何出错的。 公共卫生相关性：奖惩过程中的缺陷是酒精和物质依赖、成瘾和其他精神病理的理论基石，但对这些受到任务目标、遗传变异或压力影响的人知之甚少。这项拟议研究的总体目标是详细了解奖惩双重加工模式的遗传基础，这对改进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。

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.