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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 精神分裂症和双相情感障碍是精神综合症最长期和衰弱的一种，终生患病率约为1％，代表了主要的公共卫生问题。尽管传统上被认为是彼此不同的，但最近的工作揭示了基因组区域的大量家庭共同聚集和重叠，显示出与这两种疾病的联系并关联。阐明影响对这些疾病的敏感性和表达的特定遗传和神经机制，并解释它们之间的重叠性质，对于理解明显的精神病的必要条件和发展更有效的治疗和预防策略至关重要。为了在这些问题上获得牵引力，我们建议研究在基于人群的单一粘剂（MZ）和二氮基（DZ）双子对的基于人群基于人群的样本中的神经功能障碍和双相情感障碍的遗传。将通过结构化的临床访谈，磁共振成像（MRI）扫描和全面的神经心理学测试电池来评估参与者，我们将获得用于DNA提取和基因分型的血液样本。将使用此信息：1）阐明以剂量依赖性方式变化的神经特征，对未受影响的MZ和DZ Co-Twins的精神分裂症和双相情感障碍的遗传责任以及控制双胞胎的遗传责任，并阐明了两种综合征之间这些特征的重叠程度； 2）研究先前与精神分裂症和/或双相情感障碍有关的基因组区域，以与这些神经内表型和明显的精神病相关； 3）与未受影响的MZ Co-Twins相比，在表现出明显的精神分裂症或躁郁症的个体中独有或更严重的非遗传神经变化，并确定产科并发症和其他非遗传影响对这些神经变化的贡献。