NEURAL PHENOTYPES FOR SCHIZOPHRENIA AND BIPOLAR DISORDER

精神分裂症和双向情感障碍的神经表型

• 批准号: 8363431
• 负责人: TYRONE D CANNON
• 金额: $ 1.01万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363431
• 关键词: Bipolar Disorder; Blood specimen; Brain; Chronic; Clinical; DNA; Development; Discipline of obstetrics; Disease; Dizygotic Twins; Dose; Functional disorder; Funding; Genetic; Genomics; Genotype; Grant; Individual; Interview; Link; Magnetic Resonance Imaging; Modeling; National Center for Research Resources; Nature; Neuropsychological Tests; Participant; Phenotype; Predisposition; Prevalence; Prevention strategy; Principal Investigator; Psychotic Disorders; Public Health; Recruitment Activity; Registries; Research; Research Infrastructure; Resources; Sampling; Schizophrenia; Source; Structure; Syndrome; Traction; Twin Multiple Birth; United States National Institutes of Health; Work; computational anatomy; cost; effective therapy; endophenotype; neuromechanism; non-genetic; population based; relating to nervous system; trait; treatment strategy

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Schizophrenia and bipolar disorder are among the most chronic and debilitating of psychiatric syndromes and, with a lifetime prevalence of about 1% each, represent major public health concerns. While traditionally viewed as distinct from each other, recent work has revealed substantial familial co-aggregation and overlap in the genomic regions showing linkage and association with these two disorders. Elucidating the specific genetic and neural mechanisms influencing susceptibility to and expression of these illnesses, and explaining the nature of the overlap between them, is critical to understanding the necessary and sufficient conditions for overt psychosis and to the development of more effective treatment and prevention strategies. To gain traction on these issues, we propose to investigate the inheritance of neural dysfunctions in schizophrenia and bipolar disorder in population-based samples of monozygotic (MZ) and dizygotic (DZ) twin pairs concordant and discordant for these two conditions along with healthy control pairs recruited from the Swedish Twin Registry. Participants will be evaluated with structured clinical interviews, magnetic resonance imaging (MRI) scans of the brain, and a comprehensive neuropsychological test battery, and we will obtain blood samples for DNA extraction and genotyping. This information will be used: 1) to elucidate neural traits that vary in dose-dependent fashion with genetic liability to schizophrenia and bipolar disorder among unaffected MZ and DZ co-twins and control twins and to clarify the extent of overlap in these features between the two syndromes; 2) to investigate genomic regions previously linked to schizophrenia and/or bipolar disorder for association with these neural endophenotypes and overt psychosis; and 3) to isolate non-genetic neural changes that are unique to or more severe in individuals who manifest overt schizophrenia or bipolar disorder compared with their unaffected MZ co-twins and determine the contributions of obstetric complications and other non-genetic influences to these neural changes.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 精神分裂症和双相情感障碍是最慢性、最使人衰弱的精神综合症，每种疾病的终生患病率约为 1%，是主要的公共卫生问题。虽然传统上被认为彼此不同，但最近的研究揭示了基因组区域的大量家族共聚集和重叠，显示出与这两种疾病的联系和关联。阐明影响这些疾病的易感性和表现的特定遗传和神经机制，并解释它们之间重叠的性质，对于理解明显精神病的必要和充分条件以及制定更有效的治疗和预防策略至关重要。为了获得对这些问题的关注，我们建议在基于群体的同卵（MZ）和异卵（DZ）双胞胎样本以及健康对照对中研究精神分裂症和双相情感障碍神经功能障碍的遗传，这两种情况一致和不一致从瑞典双胞胎登记处招募。参与者将接受结构化临床访谈、大脑磁共振成像 (MRI) 扫描和综合神经心理学测试组的评估，我们将获取血液样本用于 DNA 提取和基因分型。该信息将用于：1) 阐明未受影响的同卵双胞胎和对照双胞胎中以剂量依赖性方式变化的神经特征，这些特征与精神分裂症和双相情感障碍的遗传倾向有关，并阐明这些特征在未受影响的同卵双胞胎和对照双胞胎中的重叠程度。两种综合症； 2) 研究先前与精神分裂症和/或躁郁症相关的基因组区域与这些神经内表型和明显精神病的关联； 3) 分离出与未受影响的同卵双胞胎相比，表现出明显的精神分裂症或双相情感障碍的个体特有的或更严重的非遗传性神经变化，并确定产科并发症和其他非遗传影响对这些神经的影响变化。