Genetic, Imaging, and Cognition study of Positive Valence Systems in Psychotic Syndromes

精神病综合征正价系统的遗传、影像和认知研究

• 批准号: 10468990
• 负责人: ROBERT M BILDER
• 金额: $ 63.62万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10468990
• 关键词: Address; Bayesian Modeling; Behavior; Behavior Control; Behavioral; Biological; Bipolar Disorder; Brain; Brain imaging; Candidate Disease Gene; Clinical; Cognition; Cognitive; Consensus; Consummatory Behavior; Corpus striatum structure; Data; Databases; Decision Making; Deposition; Diagnosis; Diagnostic; Diagnostic and Statistical Manual of Mental Disorders; Dimensions; Disease; Educational workshop; Etiology; Expectancy; Expenditure; First Degree Relative; Functional Magnetic Resonance Imaging; Genetic; Genetic Risk; Genotype; Health; Heritability; Image; Individual; Individual Differences; Knowledge; Laboratories; Link; Major Depressive Disorder; Measures; Mental disorders; Motivation; National Institute of Mental Health; Netherlands; Neurocognitive; Participant; Patients; Phenotype; Physicians; Population; Positive Valence; Prefrontal Cortex; Process; Protocols documentation; Research; Research Personnel; Research Project Summaries; Rewards; Risk; Sampling; Schizophrenia; Siblings; Specific qualifier value; Structure; Symptoms; Syndrome; System; Taxonomy; Testing; Variant; behavior measurement; brain circuitry; cognitive function; cognitive task; cognitive testing; cohort; comparison group; cost; design; financial incentive; genetic architecture; genetic risk factor; genetic variant; genome sequencing; genome-wide; genome-wide analysis; learning strategy; neural circuit; neuroimaging; neuropsychiatric disorder; precision medicine; psychiatric genomics; psychologic; psychotic; response; screening; trait; web-based assessment; whole genome

Project Summary The Research Domains Criteria (RDoC) initiative was developed by the NIMH to address growing concern about the validity of the Diagnostic and Statistical Manual of Mental Disorders (DSM) and its potential to limit research on mental illness. The overarching aim of RDoC to identify dimensions of brain structure and function that will possess greater biological validity than our current taxonomy holds great promise for rational diagnosis and treatment of mental illness. The proposed study aims to examine one of the core components of RDoC that is focused on reward circuits and behavior, namely the Positive Valence Systems domain (PVS). The PVS has been linked to diverse psychiatric disorders including schizophrenia, bipolar disorder and major depressive disorder. There is consensus that schizophrenia and bipolar disorder share substantial genetic risk and multiple overlapping phenotypic variations at the levels of corticostriatal brain circuits, cognitive functions, and behavior. Yet it remains unknown precisely which dimensions are shared, which may diverge between syndromes, and how the associated phenotypes relate to shared and non-shared genetic risk. The proposed research will examine the RDoC PVS domains in two large genetically informative cohorts comprising more than 5,000 individuals already ascertained in the Netherlands. Participants include 1,000 schizophrenia patients, 1,750 subjects with bipolar disorder, more than 1,000 first-degree relatives and almost 1,500 healthy comparison subjects. Extensive clinical and neurocognitive data is already available, which will contribute significantly to our understanding of basic brain circuitry that controls behavior in health and disease. Available genome-wide genotype and whole genome sequencing data provide a unique opportunity to examine the heritability of the PVS measures and its relationship with the etiology of psychiatric disorder. We will collect multi-level data pertaining to each of the four primary PVS component processes identified by the RDoC Workshop focused on Reward Seeking and Consummatory Behavior (Approach Motivation) through online assessments of these cognitive constructs. These will be further validated by in-laboratory measures using functional MRI in a subset of participants (n=500). Analyses will focus on the ventral striatal (VS) and ventromedial prefrontal cortex (vmPFC) responses to anticipation and receipt of reward. We will derive response profiles from the four PVS cognitive tests that possess greatest concurrent validity with respect to individual differences in neural circuit function. Results of this study will provide important new data about the relations of the PVS component processes proposed in RDoC to the primary neural circuits, and enable the results in our genetically informative samples to be evaluated in the context of research on a broad range of mental disorders and healthy individuals.

项目摘要 研究领域标准（RDoC）倡议是由NIMH开发的，以解决日益增长的问题 关于精神疾病诊断和统计手册（DSM）的有效性及其限制 研究精神疾病。RDoC的首要目标是确定大脑结构和功能的维度 比我们目前的分类学具有更大的生物学有效性，为合理诊断提供了巨大的希望。 和精神疾病的治疗建议的研究旨在探讨RDoC的其中一个核心组成部分 它专注于奖励电路和行为，即正价系统域（PVS）。的 PVS与各种精神疾病有关，包括精神分裂症，双相情感障碍和主要精神障碍。 抑郁症有共识认为精神分裂症和双相情感障碍有着实质性的遗传 在皮质纹状体脑回路水平的风险和多重重叠表型变异，认知 功能和行为。然而，我们仍然不清楚究竟哪些维度是共享的，哪些维度可能是不同的 综合征之间，以及相关的表型如何与共享和非共享遗传风险相关。的 拟议的研究将在两个大型遗传信息队列中检查RDoC PVS域 包括荷兰境内已查明的5,000多人。参与者包括1000名 精神分裂症患者，1,750名双相情感障碍患者，1,000多名一级亲属， 1,500名健康对照受试者。广泛的临床和神经认知数据已经可用，这将 对我们理解控制健康和疾病行为的基本脑回路有重要贡献。 可用的全基因组基因型和全基因组测序数据提供了一个独特的机会， 检查PVS指标的遗传性及其与精神疾病病因的关系。 我们将收集与四个主要PVS组件过程中的每一个相关的多层次数据， RDoC研讨会的重点是奖励寻求和完善行为（接近动机）， 在线评估这些认知结构。这些将通过实验室测量进一步验证 在一个参与者子集中使用功能性MRI（n=500）。分析将集中在腹侧纹状体（VS）和 腹内侧前额叶皮层（vmPFC）对预期和接受奖励的反应。我们将推导出 来自四个PVS认知测试的反应特征，其在以下方面具有最大的同时效度： 神经回路功能的个体差异。 本研究结果将为PVS组分过程的相互关系提供重要的新数据 在RDoC中提出的主要神经回路，并使我们的遗传信息样本的结果 在对广泛的精神障碍和健康个体进行研究的背景下进行评估。

项目成果

Construct Identification in the Neuropsychological Battery: What Are We Measuring?

• DOI: 10.1037/neu0000832
• 发表时间: 2022-06-23
• 期刊: NEUROPSYCHOLOGY
• 影响因子: 2.4
• 作者: Bilder, Robert M.;Widaman, Keith F.;Shih, Stone
• 通讯作者: Shih, Stone

Yakovlevian Torque: Something Old and Something New.

雅科夫列夫扭矩：旧的和新的。

• DOI: 10.1016/j.biopsych.2022.01.013
• 发表时间: 2022
• 期刊: Biological psychiatry
• 影响因子: 10.6
• 作者: Bilder,RobertM

Extensions of Multiple-Group Item Response Theory Alignment: Application to Psychiatric Phenotypes in an International Genomics Consortium.

多组项目反应理论比对的扩展：在国际基因组学联盟中应用于精神病学表型。

• DOI: 10.1177/0013164419897307
• 发表时间: 2020
• 期刊: Educational and psychological measurement
• 影响因子: 2.7
• 作者: Mansolf,Maxwell;Vreeker,Annabel;Reise,StevenP;Freimer,NelsonB;Glahn,DavidC;Gur,RaquelE;Moore,TylerM;Pato,CarlosN;Pato,MicheleT;Palotie,Aarno;Holm,Minna;Suvisaari,Jaana;Partonen,Timo;Kieseppä,Tuula;Paunio,Tiina;Boks,Ma
• 通讯作者: Boks,Ma