Abstract:
The Research Domain Criteria (RDoC) initiative was established by the US National Institute of Mental Health as a multilevel, disorder-agnostic framework for analysis of human psychopathology through designated domains and constructs, including the \"Positive Valence Systems\" domain focused on reward-related behavior. This study investigates the reward valuation subconstruct of \"effort\" and its association with genetic markers, functional neurobiological pathways, and polygenic risk scores for psychopathology in 1215 children aged 6-12 and their parents (n = 1044). All participants completed the effort expenditure for rewards task (EEfRT), which assesses \"effort\" according to two quantitative measures: hard-task choice and reward sensitivity. Genetic association analyses were undertaken in MAGMA, utilizing EEfRT outcome variables as genome-wide association studies phenotypes to compute SNP and gene-level associations. Genome-wide association analyses found two distinct genetic loci that were significantly associated with measures of reward sensitivity and a separate genetic locus associated with hard task choice. Gene-set enrichment analysis yielded significant associations between \"effort\" and multiple gene sets involved in reward processing-related pathways, including dopamine receptor signaling, limbic system and forebrain development, and biological response to cocaine. These results serve to establish \"effort\" as a relevant construct for understanding reward-related behavior at the genetic level and support the RDoC framework for assessing disorder-agnostic psychopathology.
摘要:
研究领域标准(RDoC)倡议是由美国国家心理健康研究所建立的多层次,通过指定领域和结构分析人类精神病理学的障碍-不可知论框架,包括专注于奖励相关行为的“正价系统”领域。本研究调查了“努力”的奖励评估子结构及其与遗传标记的关联,功能性神经生物学通路,1215名6-12岁儿童及其父母(n=1044)的精神病理学多基因风险评分。所有参与者都完成了奖励任务的努力支出(EEfRT),它根据两个量化指标来评估“努力”:艰巨的任务选择和奖励敏感度。在MAGMA中进行了遗传关联分析,利用EEfRT结果变量作为全基因组关联研究表型来计算SNP和基因水平关联。全基因组关联分析发现了两个不同的遗传基因座,它们与艰巨任务选择的度量显着相关,而另一个遗传基因座与奖励敏感性相关。基因集富集分析产生了“努力”和参与奖励处理相关途径的多个基因集之间的显著关联,包括多巴胺受体信号,边缘系统和前脑发育,和对可卡因的生物反应。这些结果有助于将“努力”确立为在遗传水平上理解奖励相关行为的相关结构,并支持用于评估与疾病无关的心理病理学的RDoC框架。