Schizophrenia genetics, neural and cognitive phenotypes, and social functioning

精神分裂症遗传学、神经和认知表型以及社会功能

基本信息

批准号：
8649516
负责人：
Laura Thi Germine
金额：
$ 4.92万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-02-01 至 2017-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8649516
关键词：
Amygdaloid structure Architecture Area Behavior Behavioral Binding Brain Chronic Cognitive Complex Data Data Collection Diagnosis Enrollment First Degree Relative Foundations General Hospitals Genetic Genetic Risk Genetic Variation Genome Genomics Heritability Image Individual Inferior frontal gyrus Internet Intervention Jordan Lead Light Link Mails Massachusetts Measures Medial Mental disorders Methods Motivation Neurocognitive Neurophysiology - biologic function Neuropsychology Participant Pathogenesis Pathway interactions Patients Phenotype Play Positioning Attribute Prefrontal Cortex Prevention Research Research Training Resources Risk Role Sampling Schizophrenia Single Nucleotide Polymorphism Social Functioning Social Perception Sorting - Cell Movement Structure Superior temporal gyrus System Testing Thick Traction Training Universities Variant base brain volume career cognitive function cognitive neuroscience cohort genetic association genetic risk factor genetic variant genome wide association study genome-wide information processing neuroimaging neuromechanism novel public health relevance relating to nervous system risk variant skills social social cognition trait

项目摘要

DESCRIPTION (provided by applicant): Deficits in social functioning are consistently linked with schizophrenia and schizophrenia risk. Research has uncovered specific neural and cognitive mechanisms that contribute to social functioning in healthy individuals, and abnormalities in some of these mechanisms have been identified in both schizophrenia patients and their unaffected first-degree relatives [1-3]. This suggests that genetic risk for schizophreni may manifest in terms of variations in these basic neural and cognitive mechanisms, even in individuals without a mental disorder. Recent genetic discovery efforts have begun to unravel the genetic architecture of schizophrenia, yielding (1) methods for estimating schizophrenia polygenic risk, or the aggregate risk arising from variations in single-nucleotide polymorphisms across the entire genome [4], and (2) specific genetic variants that are associated with schizophrenia, even after genome-wide statistical correction [5]. With these new discoveries, there are new opportunities for identifying potential pathways leading from genetic risk to deficit in neural function, information processing, and behavior that ultimately may lead to schizophrenia. Here, I focus on the relationship between recently identified genetic predictors and intermediate neural and cognitive phenotypes related to social functioning. The current proposal aims to answer the following questions: (1) How much of the variation in intermediate neural/cognitive phenotypes related to social functioning can be explained by variations in single-nucleotide polymorphisms? (2) Does estimated polygenic risk for schizophrenia predict variations in social functioning phenotypes? (3) Do recently identified schizophrenia genetic risk variants predict variations in social functioning phenotypes? The proposed research uses intermediate phenotypes as a way of gaining traction on the mechanisms that lead from validated genetic risk factors to mental disorders. The proposed research may enable the identification of pathways through which genetic risk factors influence risk for developing schizophrenia, through their action on particular aspects of neural architecture and social cognition. Identification of these specific pathways will suggest new hypotheses for the pathogenesis of schizophrenia and offer potential targets for treatment, intervention, and further research.

描述（由申请人提供）：社会功能的缺陷始终与精神分裂症和精神分裂症的风险联系在一起。研究发现了有助于健康个体的社会功能的特定神经和认知机制，在精神分裂症患者及其未受影响的一级亲戚中都发现了其中一些机制的异常[1-3]。这表明，精神分裂症的遗传风险可能会在这些基本神经和认知机制的变化方面表现出来，即使在没有精神障碍的个体中也是如此。最近的遗传发现工作已经开始阐明精神分裂症的遗传结构，产生（1）估计精神分裂症多基因风险的方法，或者是由于单个核苷酸多态性在整个基因组中的变化而产生的总体风险[4]，以及（2）特定的遗传变异，这些特定遗传变异量与基因 - 以及基因 - 以及基因 - 以及基因之间相关。有了这些新发现，有一些新的机会来确定从遗传风险到神经功能，信息处理和行为的赤字的潜在途径，最终可能导致精神分裂症。在这里，我关注最近确定的遗传预测因子与与社会功能有关的中间神经和认知表型之间的关系。当前的提案旨在回答以下问题：（1）可以通过单核苷酸多态性的变化来解释与社会功能相关的中间神经/认知表型的多少变化？（2）精神分裂症的估计多基因风险是否可以预测社会功能表型的变化？（3）最近是否发现精神分裂症遗传风险变异可以预测社会功能表型的变化？拟议的研究使用中间表型作为一种从验证的遗传危险因素到精神障碍的机制上吸引的一种方法。拟议的研究可以通过对神经建筑和社会认知的特定方面的行动来影响遗传危险因素影响发展精神分裂症的风险的途径。这些特定途径的识别将提出精神分裂症发病机理的新假设，并为治疗，干预和进一步研究提供潜在的靶标。