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: 7502964
• 负责人: MARINA MYLES-WORSLEY
• 金额: $ 11.5万
• 依托单位: UPSTATE MEDICAL UNIVERSITY
• 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 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7502964
• 关键词: 18 year old; Adolescent; Affect; Age of Onset; Applications Grants; Characteristics; Clinical; Clinical Data; Counseling; Data; Data Analyses; Development; Early Diagnosis; Environmental Risk Factor; Family; Foundations; Functional disorder; Genetic; Genetic Predisposition to Disease; Genetic Risk; Grant; Individual; Intervention; Manuscripts; Measures; Micronesia; Modeling; Neurocognitive; Numbers; Outcome; Palau; Paper; Parents; Patients; Phase; Population; Preparation; Prospective Studies; Psychiatric therapeutic procedure; Psychopathology; Psychotic Disorders; Range; Relative (related person); Reporting; Research; Research Design; Risk; Risk Estimate; Sampling; Schizophrenia; Staging; Substance abuse problem; TNFRSF5 gene; Testing; Youth; base; clinical phenotype; density; endophenotype; family genetics; follow-up; genetic epidemiology; neurophysiology; neuropsychiatry; neuropsychological; oculomotor; psychoeducational intervention; psychosocial; sensory gating; trait

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.

这是我们对帕劳精神分裂症遗传病因学研究的竞争性延续，帕劳是密克罗尼西亚的一个地理和种族孤立的地方，不是近亲繁殖的。我们帕劳研究的流行病学阶段的完成为拟议的关于现已确定的大型多发性精神分裂症家庭中的高危(HR)后代的前瞻性研究奠定了基础。我们计划不仅研究受影响父母的所有14-18岁青少年子女(约100人)，而且研究可能携带精神疾病遗传责任的未受影响父母的青少年子女(约200人)。这300名HR青少年将与100名被确定为行为但没有遗传风险的14-18岁青少年(没有接受药物滥用咨询、心理社会咨询或精神治疗的近亲的青少年)和100名正常青少年对照组进行比较。所有受试者都将接受一系列临床/心理社会和神经心理学测量以及精神分裂症的两种神经生理内表型的综合评估，并对精神病理学的发展进行纵向跟踪，以实现三个具体目标。1.描述多胎家庭HR后代中精神分裂症的遗传流行病学。2.开发和测试病因学模型，描述遗传倾向、环境因素和个人特征如何相互作用，导致精神分裂症谱系精神病理学。3.描述精神分裂症发展阶段的现象学，以便于早期发现和干预。我们提议的研究具有许多独特的特征，这些特征将极大地增强其产生的信息。与以前对HR后代的研究相比，我们将能够采样更广泛的与精神分裂症患者的关系，以及可以传播精神分裂症谱系精神病理学的更广泛的父母临床表型。此外，我们研究设计的一个独特部分是将遗传的HR受试者与一组行为但不是遗传的HR受试者进行比较，这可能有助于将精神分裂症的环境前体与遗传易感性分开。此外，我们的研究建议通过增加几个指标来填补对MR后代评估的现有空白，包括精神分裂症的两个有希望的内表型，眼球跳动功能障碍和P50感觉门控缺陷。

项目成果

Recurrence risk to offspring in extended multiplex schizophrenia pedigrees from a Pacific Island isolate.

太平洋岛屿分离株的多重多重精神分裂症谱系的后代复发风险。

• DOI: 10.1002/ajmg.b.30384
• 发表时间: 2007
• 期刊: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
• 作者: Myles-Worsley,Marina;Tiobech,Josepha;Blailes,Francisca;Yano,VictorM;Faraone,StephenV
• 通讯作者: Faraone,StephenV

Mutation screening of a neutral amino acid transporter, ASCT1, and its potential role in schizophrenia.

中性氨基酸转运蛋白 ASCT1 的突变筛选及其在精神分裂症中的潜在作用。

• DOI: 10.1097/00041444-200010020-00004
• 发表时间: 2000
• 期刊: Psychiatric genetics
• 影响因子: 0.9
• 作者: Bennett,PJ;Hoff,M;Rosenthal,J;Zhao,M;Coon,H;Myles-Worsley,M;Byerley,WF
• 通讯作者: Byerley,WF

P50 sensory gating in multiplex schizophrenia families from a Pacific island isolate.

来自太平洋岛屿分离株的多重精神分裂症家族中的 P50 感觉门控。

• DOI: 10.1176/appi.ajp.159.12.2007
• 发表时间: 2002
• 期刊: The American journal of psychiatry.
• 作者: Myles-Worsley,Marina

The Palau Early Psychosis Study: distribution of cases by level of genetic risk.

帕劳早期精神病研究：按遗传风险水平划分的病例分布。

• DOI: 10.1002/ajmg.b.30362
• 发表时间: 2007
• 期刊: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
• 作者: Myles-Worsley,Marina;Blailes,Francisca;Ord,LisaM;Weaver,Starla;Dever,Gregory;Faraone,StephenV
• 通讯作者: Faraone,StephenV

The Palau Early Psychosis Study: neurocognitive functioning in high-risk adolescents.

帕劳早期精神病研究：高危青少年的神经认知功能。

• DOI: 10.1016/j.schres.2006.08.003
• 发表时间: 2007
• 期刊: Schizophrenia research
• 影响因子: 4.5
• 作者: Myles-Worsley,Marina;Ord,LisaM;Ngiralmau,Hilda;Weaver,Starla;Blailes,Francisca;Faraone,StephenV
• 通讯作者: Faraone,StephenV