Transmission of Vulnerability Factors for Schizophrenia

这个项目的目的是测试关键的假设，关于个人的可测量的无症状特征，反映他们的易感性精神分裂症的传输。识别这些脆弱性因素及其相互关系内和跨生物亲属的精神分裂症患者应使我们能够加快我们的进展，在检测精神分裂症的遗传贡献的性质。 下一个项目阶段将主要集中在神经认知功能障碍之间的相互关系，部分介导的前额叶皮层和内侧颞区，在这两个地区，微妙的结构异常，精神分裂症的易感性。 我们在神经认知功能和区域脑结构中寻找脆弱性因素，是试图识别中间表型或“内表型”，它们在因果链中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、工作记忆和陈述性记忆的巩固等领域。 MRI的形态测量指标将强调前额叶皮层和内侧颞叶结构的细微体积和灰质密度变化。 使用家庭数据，我们将测试这些脑结构异常，其假设的相关神经认知缺陷，精神分裂症谱系障碍之间的关系是否与一个共同的潜在的家族/遗传因素，或一个替代模型，其中有一个以上的维度的家族/遗传易感性精神分裂症是一致的一级亲属。 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学匹配的社区对照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.