NEUROPHYSIOLOGY STUDIES IN SCHIZOPHRENIA AND RELATED DISORDERS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。大量证据表明，精神分裂症是一种遗传性疾病，基因型表现为易患病。分裂型及相关人格和平滑追求眼动（SPEM）异常在精神分裂症患者的非患病亲属中非常普遍，并标志着精神分裂症的遗传易感性。我们的建议是基于这样一个前提，即在存在遗传易感性的情况下，其他非基因型因素会导致疾病的显性表达。非基因型因素可能是发育过程中的环境压力或对正常大脑发育至关重要的非特异性遗传因素。该协议的总体目标是：(1)改进检查眼球运动的方法，以定义标志遗传倾向性的认知和眼运动过程；(2)描述易感人群眼动异常的临床和认知相关因素；(3)描述可能导致先证者患病的非基因型因素的推定标记；(4)以平滑追求眼动异常作为表型进行正式的遗传连锁分析。本研究的目的之一是检查可能在精神分裂症病因中起作用的潜在产前压力因素。我们假设，在一个家庭中，有或没有遗传缺陷的个体，暴露于假定的压力因素的概率是相等的。在基因脆弱的个体中，那些暴露在压力下的人会患上显性疾病，而没有暴露在压力下的脆弱个体只会携带表现型标记。

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. Wealth of evidence suggests that schizophrenia is a genetic illness and the genotype is expressed as liability to illness. Schizotypal and related personalities and smooth pursuit eye movement (SPEM) abnormalities are highly prevalent in non-ill relatives of schizophrenic patients and mark the genetic liability to schizophrenia. Our proposal is based on the premise that in the presence of the genetic vulnerability, other non-genotypic factors lead to the overt expression of the illness. Non-genotypic factors are likely to be either environmental stress during development or non specific genetic factors critical for normal brain development. The broad goals of the protocol are: (1) Refine methods of examining eye movements in order to define the cognitive and ocular motor processes which mark the genetic liability; (2) Describe clinical and cognitive correlates of eye movement abnormality in vulnerable individuals; (3) Describe putative markers of non-genotypic factors which may have contributed to the development of the illness in the proband; and, (4) Conduct formal genetic linkage analysis using smooth pursuit eye movement abnormality as a phenotype. One of the goals of this study is to examine potential prenatal stress factors that may play a role in the etiology of schizophrenia. We hypothesize that within a family, individuals with and without the genetic liability, have equal probability of being exposed to putative stress factors. Of the genetically vulnerable individuals, those who are exposed to the stress will develop overt illness, whereas vulnerable individuals not exposed to the stress will only carry the phenotypic marker.