Transmission of Vulnerability Factors for Schizophrenia

该项目旨在测试关于个体可测量的非症状特征的传播的关键假设，这些特征反映了他们患精神分裂症的易感性。确定这些易感性因素及其在精神分裂症患者的生物学亲属内部和之间的相互关系，将使我们能够加快在检测精神分裂症遗传贡献性质方面的进展。下一个项目阶段将主要集中在部分由前额叶皮层和内侧颞区介导的神经认知功能障碍之间的相互关系，这两个区域的细微结构异常，以及精神分裂症的易感性。我们对神经认知功能和区域大脑结构中的易感性因素的研究是试图确定中间表型或“内表型”，它比精神分裂症本身在因果链上更接近基因的影响。神经认知测量将涉及注意力、工作记忆和陈述性记忆巩固的领域。MRI的形态测量指数将强调前额叶皮层和内侧颞叶结构中细微的体积和灰质密度改变。使用家庭数据，我们将测试这些大脑结构异常、假设的相关神经认知缺陷和一级亲属的精神分裂症谱系障碍之间的关系是否与一个共同的潜在家族/遗传因素一致，或者是一个替代模型，其中存在多个维度的精神分裂症家族/遗传倾向性。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者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.