FAMILY-GENETIC STUDY OF YOUTH AT RISK FOR SCHIZOPHRENIA

描述(申请人摘要)：这是一份竞争性的申请 继续我们对帕劳精神分裂症遗传病因学的研究， 密克罗尼西亚的一种地理和种族隔离，不是近亲繁殖的。这个 我们帕劳流行病学研究阶段的完成奠定了 为拟议中的高危(HR)后代前瞻性研究奠定基础 现已确定的大型多发性精神分裂症家族。我们 计划不仅研究受影响的所有14-18岁青少年的后代 父母(约100人)，也是青春期未受影响的后代 可能是精神病基因携带者的父母 (约200个)。这300名HR青少年将与100名14-18岁的青少年进行比较 被确认为行为上但不存在遗传风险的年龄段儿童 (没有受影响的近亲被转介的青少年 药物滥用咨询、心理社会咨询或精神治疗) 以及100名正常青少年对照组。所有科目都将全面 通过一系列临床/心理社会和神经心理学评估 措施加两种神经生理内表型对精神分裂症和 对精神病理学的发展进行纵向随访，以便 实现三个具体目标。1.描述流行性感冒的遗传流行病学 多胎家庭中HR后代中的精神分裂症。2.开发和测试 病因学模型描述了遗传因素、环境因素、 个体特征相互作用，导致精神分裂症谱系精神病理。 3.描述精神分裂症发展阶段的现象学 促进早期发现和干预。我们建议的研究有多项 将极大地增强其生成的信息的独特特征。 与以前对HR后代的研究相比，我们将能够收集更广泛的样本 与精神分裂症患者的一系列关系和更广泛的 可传递精神分裂症谱系的父母临床表型 精神变态学。此外，我们研究设计的一个独特组成部分是比较 遗传HR受试者有一组行为上的，但不是遗传上的， 人力资源受试者，这可能有助于理清环境前体 遗传缺陷导致的精神分裂症。此外，我们的研究建议填补 通过增加几项措施，在评估MR后代方面存在差距 包括精神分裂症的两种有希望的内表型，眼球跳动 功能障碍和P50感觉门控缺陷。

DESCRIPTION (Applicant's abstract): This is an application for competitive continuation of our research on the genetic etiology of schizophrenia in Palau, a geographic and ethnic isolate in Micronesia that is not inbred. The completion of the epidemiological phase of our Palau study has laid the foundation for the proposed prospective study of high-risk (HR) offspring in the large multiplex schizophrenia families that have now been identified. We plan to study not only all 14-18 year-old adolescent offspring of affected parents (approximately 100) but also the adolescent offspring of unaffected parents who are possible carriers of a genetic liability for psychotic illness (approximately 200). These 300 HR adolescents will be compared to 100 14-18 year olds who are identified as behaviorally but not genetically at risk (adolescents with no close affected relatives who have been referred for substance abuse counseling, psychosocial counseling, or psychiatric treatment) and 100 normal adolescent controls. All subjects will be comprehensively assessed with a battery of clinical/psychosocial and neuropsychological measures plus two neurophysiological endophenotypes for schizophrenia and followed up longitudinally for the development of psychopathology in order to accomplish three specific aims. 1. Describe the genetic epidemiology of schizophrenia in HR offspring within multiplex families. 2. Develop and test etiological models that describe how genetic liability, environmental factors, and individual traits interact to cause schizophrenia spectrum psychopathology. 3. Describe the phenomenology of schizophrenia in its developmental stages to facilitate early detection and intervention. Our proposed study has a number of unique characteristics that will greatly enhance the information it generates. Compared to prior studies of HR offspring, we will be able to sample a broader range of relationships to schizophrenic patients and a broader range of parental clinical phenotypes that can transmit schizophrenia spectrum psychopathology. Also, a unique component of our study design is the comparison of genetically HR subjects with a group of behaviorally, but not genetically, HR subjects, which may help to disentangle environmental precursors of schizophrenia from genetic liability. Furthermore, our study proposes to fill existing gaps in the assessment of MR offspring by adding several measures including two promising endophenotypes for schizophrenia, saccadic ocular motor dysfunction and P50 sensory gating deficits.