Transmission of Vulnerability Factors for Schizophrenia

该项目旨在测试有关个人可测量的无症状特征的传播的关键假设，这些特征反映了他们对精神分裂症的易感性。确定这些脆弱因素及其在精神分裂症患者的亲生亲属内部和之间的相互关系将使我们能够加快我们在检测精神分裂症的遗传因素性质方面的进展。下一个项目阶段将主要关注部分由前额叶皮质和内侧颞区介导的神经认知功能障碍、这两个区域的细微结构异常和精神分裂症易感性之间的相互关系。我们寻找神经认知功能和大脑区域结构中的易感因素，是为了找出中间表型或“内表型”，这些表型在因果关系链上比精神分裂症本身更接近基因的影响。神经认知测量将涉及注意力、工作记忆和巩固陈述性记忆的领域。MRI的形态计量学指数将强调前额叶皮质和内侧颞叶结构中微妙的体积和灰质密度变化。利用家庭数据，我们将测试这些大脑结构异常、它们假想的相关神经认知缺陷和精神分裂症一级亲属之间的关系是否与一个共同的潜在家庭/遗传因素一致，或者是否与精神分裂症的家庭/遗传倾向不止一个维度的替代模式一致。这些目标将通过收集精神分裂症先证者及其一级亲属以及人口统计匹配的社区控制组及其一级亲属的数据来实现。

This project is designed to test key hypotheses regarding the transmission of measurable nonsymptomatic characteristics of individuals that reflect their predisposition to schizophrenia. Identification of such vulnerability factors and of their interrelationships within and across biological relatives of patients with schizophrenia should allow us to accelerate our progress in detecting the nature of genetic contributions to schizophrenia. The next project phase will primarily focus on the interrelationships among neurocognitive dysfunctions mediated partially by the prefrontal cortex and the medial temporal region, subtle structural anomalies in these two regions, and liability to schizophrenia. Our search for vulnerability factors in neurocognitive functioning and regional brain structure is an attempt to identify intermediate phenotypes or "endophenotypes" that are closer in causal chains to the effects of genes than is schizophrenia itself. Neurocognitive measures will involve the domains of attention, working memory, and consolidation of declarative memory. Morphometric indices from MRI will emphasize subtle volume and gray matter density alterations in the prefrontal cortex and medial temporal structures. Using family data, we will test whether the relationships between these brain structural anomalies, their hypothesized associated neurocognitive deficits, and schizophrenia spectrum disorder across first-degree relatives are consistent with one common underlying familial/genetic factor, or an alternative model in which there is more than one dimension of familial/genetic liability to schizophrenia. These goals will be addressed through data collection with schizophrenic probands and their first-degree relatives as well as with demographically matched community controls and their first-degree relatives.