FAMILY-GENETIC STUDY OF YOUTH AT RISK FOR SCHIZOPHRENIA

对有精神分裂症风险的青少年进行家族遗传学研究

• 批准号: 6861135
• 负责人: MARINA MYLES-WORSLEY
• 金额: $ 54.23万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6861135
• 关键词: Asians; adolescence (12-20); behavioral /social science research tag; behavioral genetics; clinical research; disease /disorder etiology; evoked potentials; family genetics; genetic markers; genetic susceptibility; genotype; human genetic material tag; human subject; linkage mapping; mental disorder diagnosis; neuropsychological tests; phenotype; psychopathology; psychophysiology; schizophrenia; smooth pursuit eye movement

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.

描述（申请人摘要）：这是一个竞争性的应用程序 继续我们对帕劳精神分裂症遗传病因学的研究， 密克罗尼西亚的一个地理上和种族上孤立的非近亲繁殖的地区。的 我们帕劳研究的流行病学阶段的完成奠定了 这是对高风险（HR）后代进行前瞻性研究的基础， 现在已经确定的大型多重精神分裂症家族。我们 计划不仅研究受影响的所有14-18岁青少年后代， 父母（约100），但也未受影响的青少年后代 可能携带精神病遗传易感性的父母 （约200人）。这300名HR青少年将与100名14-18 被确定为在行为上但在遗传上没有风险的10岁奥尔兹 （没有受影响近亲的青少年， 物质滥用咨询、心理社会咨询或精神病治疗） 和100名正常青少年对照组。所有科目将全面 通过一系列临床/心理社会和神经心理学评估 精神分裂症的两种神经生理学内表型， 对精神病理学的发展进行纵向随访， 实现三个具体目标。1.描述遗传流行病学 多重家系中HR后代精神分裂症2.开发和测试 病因学模型描述了遗传易感性，环境因素， 和个体特征相互作用导致精神分裂症谱系的精神病理学。 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。我们提出的研究有一些 独特的特性，这将大大增强它产生的信息。 与先前对HR后代的研究相比，我们将能够对更广泛的样本进行采样。 与精神分裂症患者的关系以及更广泛的 可传递精神分裂症谱系的父母临床表型 精神病理学此外，我们研究设计的一个独特组成部分是比较 一组行为上，但不是基因上， 人力资源科目，这可能有助于解开环境的前兆， 精神分裂症的遗传倾向此外，我们的研究建议填补 通过增加几项措施，消除MR后代评估中存在的差距 包括精神分裂症的两种有希望的内表型，扫视性眼球运动， 功能障碍和P50感觉门控缺陷。