NEURAL PHENOTYPES FOR SCHIZOPHRENIA AND BIPOLAR DISORDER

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 精神分裂症和双相情感障碍是最慢性和使人衰弱的精神综合征之一，终生患病率各约为1%，代表了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大量的家族性共聚集和基因组区域的重叠，显示了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。为了获得这些问题的牵引力，我们建议调查遗传神经功能障碍的精神分裂症和双相情感障碍的单卵（MZ）和双卵（DZ）的双胞胎对这两种条件的一致性和不一致的人口为基础的样本，沿着健康对照对从瑞典双胞胎登记处招募。参与者将通过结构化临床访谈，大脑磁共振成像（MRI）扫描和综合神经心理学测试电池进行评估，我们将获得血液样本用于DNA提取和基因分型。此信息将用于：1）阐明在未受影响的同卵双生子和异卵双生子同卵双生子和对照双生子中，神经性状以剂量依赖方式变化，并具有精神分裂症和双相情感障碍的遗传易感性，并阐明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;和3）分离非遗传性神经变化，所述非遗传性神经变化对于表现出明显精神分裂症或双相情感障碍的个体而言是独特的，或者与其未受影响的同卵双生子相比，在表现出明显精神分裂症或双相情感障碍的个体中更严重，并确定产科并发症和其他非遗传性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.