INVESTIGATION ON THE MOVEMENT ABNORMALITIES & GENETICS OF SCHIZOPHRENIA (IMAGES)

描述（由申请人提供）：本提案是一项努力和长期国际合作的一部分，目的是在安第斯中部地区的初级卫生保健环境中开发精神疾病的遗传流行病学和人类学研究项目，该地区由Kolla人居住，横跨阿根廷北部、玻利维亚和秘鲁。该地区的科拉人，以Tawantisuyu的古名而闻名，尽管不同程度地使用克丘亚语（他们的母语）和西班牙语，但在文化和种族上是同质的。我们在阿根廷北部开始了这项工作，培训当地社区成员担任检测和识别严重精神疾病的初级卫生工作者，并培训熟悉科拉文化和语言的精神卫生专业人员使用经跨文化研究验证的标准化诊断和认知评估工具。这项R21建议的重点是能力建设，培训当地精神卫生人员使用标准化诊断和神经心理评估，并翻译成母语和为此目的验证工具。作为验证过程的一部分，我们建议进行试点评估的主题与精神分裂症，他们的一级亲属，和匹配的人口控制，以下模型的一个正在进行的，独立资助的，遗传研究的一个内表型的抗精神病药的天真的人与精神分裂症。帕金森综合征在未接受过抗精神病药物治疗的精神分裂症患者中非常普遍，其存在与抗精神病药物诱导的副作用的易感性更高、缺乏治疗依从性和预后较差相关。此外，帕金森综合征可能与精神分裂症内表型相关的缺陷综合征密切相关，与吸烟呈负相关。我们已经确定了一个人口的精神分裂症患者，由于地理和语言的困难，很大程度上是天真的抗精神病药物治疗的整个病程。在阿根廷胡胡伊省正在进行的数据收集旨在研究这些患者、其一级亲属和文化上适当的对照组的运动障碍的临床特征、认知表现、吸烟习惯、影像学发现和遗传学。现在，我们建议翻译，改编和验证的评估工具，在克丘亚语，以扩大样本，在同一种族群体在阿根廷，秘鲁和玻利维亚的完整的多重谱系。此外，我们建议在多元家庭中进行试点数据收集，长期目标是开展以家庭为基础的关联遗传研究，作为未来拨款申请的一部分。公共卫生相关性：该项目的潜在影响怎么强调都不为过，因为：1）它将为双语临床医生提供使用和验证标准化神经精神病学评估工具的基本培训，这些工具在文化上适合Kolla人自己的语言，从而消除这些社区获得精神保健的巨大障碍; 2）它将有助于建立一个讲盖丘亚语的人获得精神保健的系统（美洲人数最多的语言少数群体），建立了一个目前尚不存在的讲盖丘亚语的心理健康专业人员工作网络; 3）基于经验的精神症状的现象学描述的可用性将为专注于精神疾病的传统医学概念的研究提供独特的工具;最后，所提议的研究的主要相关性在于睾丸的可能性，如果神经生物学定义良好的个体特征集是遗传决定的。由于这些缺陷可能早于精神病的发作，我们相信我们的策略可能会提供早期发现和早期干预的工具，可能会导致预防精神分裂症风险受试者的精神病。我们预计，我们的研究策略可能会指出新的方法来研究和解决精神分裂症患者对尼古丁依赖的脆弱性增加。

DESCRIPTION (provided by applicant): This proposal is part of an effort and long range international collaboration to develop research projects in genetic epidemiology and anthropology of mental illnesses in a primary health care setting in the Central Andean region populated by Kolla people, spanning the north of Argentina, Bolivia and Peru. The Kolla people of this region, known by the ancient name of Tawantisuyu, is homogeneous culturally and ethnically in spite of varying degrees of bilinguality of Quechua (their native language) with Spanish. We began this effort in the north of Argentina, training local community members acting as primary health agents in the detection and recognition of severe mental illness, as well as the training of mental health professionals familiar with Kolla culture and language in the use of standardized diagnostic and cognitive assessment instruments that have been validated in transcultural studies. This R21 proposal focuses on capacity building, training of local mental health personnel on the use of standardized diagnosis and neuropsychological assessment, and translation to the native language and validation of the instruments for this purpose. As part of the validation process we propose to carry out a pilot evaluation of subjects with schizophrenia, their first degree relatives, and matched population controls, following the model of an ongoing, independently funded, genetic study of an endophenotype in neuroleptic naive persons with schizophrenia. Parkinsonism is highly prevalent in neuroleptic-naive patients with schizophrenia, and its presence is associated with greater susceptibility to neuroleptic-induced side effects, lack of treatment compliance, and poorer outcome. Also, parkinsonism may be closely related with the deficit syndrome associated with an endophenotype of schizophrenia, and negatively associated with smoking. We have identified a population of patients with schizophrenia that, due to geographical and language difficulties, are largely naive to antipsychotic drug treatment throughout the course of illness. Ongoing data collection in the province of Jujuy, Argentina, aims to study the clinical characteristics, cognitive performance, smoking habits, imaging findings, and genetics of the movement disorder in these patients, their first degree relatives, and culturally appropriate controls. Now we propose to translate, adapt and validate the assessment tools in Quechua language in order to expand the sample to full multiplex pedigrees in the same ethnic group in Argentina, Peru and Bolivia. Additionally, we propose to pilot data collection on multiplex families with the long term goal of carrying out family-based association genetic studies as part of future grant applications. PUBLIC HEALTH RELEVANCE: The potential impact of this project cannot be overemphasized, in that 1) it will provide essential training for bilingual clinicians in the use and validation of standardized neuropsychiatry assessment tools, culturally adapted to the Kolla population in their own language, thus eliminating an enormous barrier to access to mental health care for these communities; 2) it will help build a system of access to mental health care by Quechua speaking persons (the most numerous language minority in the Americas), by creating a working network of Quechua-speaking mental health professionals which currently does not exist; 3) availability of empirically based, phenomenological descriptions of mental symptoms will provide a unique tool for studies focusing on traditional medicine conceptions of mental illness; and lastly, the major relevance of the proposed research lies on the possibility of testis if a neurobiologically well defined set of individual characteristics is genetically determined. Because these deficits possibly predate the onset of psychosis, we believe our strategy might provide tools for early detection and early intervention, possibly leading to prevention of psychosis in subjects at-risk for schizophrenia. We anticipate that our research strategy may indicate new ways to study and address the increased vulnerability of schizophrenic patients to nicotine dependence.