NEURAL PHENOTYPES FOR SCHIZOPHRENIA AND BIPOLAR DISORDER

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 精神分裂症和双相情感障碍是最慢性和最令人衰弱的精神综合症之一，终身患病率约为1%，是主要的公共卫生问题。虽然传统上被认为是彼此不同的，但最近的工作揭示了与这两种疾病相关的基因组区域中大量的家族共同聚集和重叠。阐明影响这些疾病易感性和表达的特定遗传和神经机制，并解释它们之间重叠的性质，对于理解显性精神病的必要条件和充分条件以及开发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，我们建议调查精神分裂症和双相情感障碍的神经功能障碍的遗传情况，研究对象是符合和不符合这两种情况的同卵和异卵双胞胎对，以及从瑞典双胞胎登记处招募的健康对照对。参与者将接受结构化的临床访谈、脑部磁共振成像(MRI)扫描和全面的神经心理学测试组合的评估，我们将获取血液样本进行DNA提取和基因分型。这些信息将被用于：1)阐明在未受影响的MZ和DZ同卵双胞胎和对照双胞胎中，精神分裂症和双相情感障碍的遗传易感性随剂量依赖而变化的神经特征，并澄清两个症状之间这些特征的重叠程度；2)调查以前与精神分裂症和/或双相情感障碍有关的基因组区域，以确定是否与这些神经内表型和显性精神病有关；以及3)分离对于表现出明显精神分裂症或双相情感障碍的个体，与其未受影响的MZ同卵双胞胎相比，独特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变化的贡献。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.