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

描述（由申请人提供）：该提案是一项长期国际合作的一部分，旨在在阿根廷北部、玻利维亚和秘鲁北部科拉人居住的安第斯中部地区的初级卫生保健机构中开展遗传流行病学和精神疾病人类学研究项目。这个地区的科拉人，古称塔万提苏宇，尽管克丘亚语（他们的母语）和西班牙语的双语程度不同，但在文化和种族上都是同质的。我们在阿根廷北部开始这项工作，培训作为初级保健代理人的当地社区成员检测和识别严重精神疾病，并培训熟悉科拉文化和语言的精神保健专业人员使用标准化诊断和认知评估工具，这些工具已在跨文化研究中得到验证。这项R21提案的重点是能力建设，培训当地精神卫生人员使用标准化诊断和神经心理学评估，并为此目的翻译成母语和验证工具。作为验证过程的一部分，我们建议对精神分裂症患者、他们的一级亲属和匹配的人群对照进行试点评估，遵循正在进行的、独立资助的精神分裂症抗精神病药初始患者的内表型遗传研究模型。帕金森病在未使用抗精神病药物的精神分裂症患者中非常普遍，其存在与抗精神病药物引起的更大副作用易感性、缺乏治疗依从性和预后较差有关。此外，帕金森病可能与精神分裂症内表型相关的缺陷综合征密切相关，与吸烟负相关。我们已经确定了一群精神分裂症患者，由于地理和语言上的困难，在整个疾病过程中，抗精神病药物治疗在很大程度上是新手。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者的临床特征、认知表现、吸烟习惯、影像学表现和运动障碍的遗传学。现在我们建议翻译、调整和验证克丘亚语的评估工具，以便将样本扩展到阿根廷、秘鲁和玻利维亚同一族群的完整多元谱系。此外，我们建议对多重家庭进行试点数据收集，其长期目标是开展基于家庭的关联遗传研究，作为未来拨款申请的一部分。公共卫生相关性：这个项目的潜在影响怎么强调都不过分，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应科拉人自己的语言，从而消除这些社区获得精神卫生保健的巨大障碍；2)通过建立目前尚不存在的说克丘亚语的心理健康专业人员工作网络，帮助建立一个克丘亚语人（美洲人数最多的语言少数群体）获得心理保健服务的系统；3)基于经验的精神症状现象学描述的可用性将为关注精神疾病的传统医学概念的研究提供独特的工具；最后，所提出的研究的主要相关性在于，如果一组神经生物学上定义良好的个体特征是由基因决定的，那么睾丸的可能性。因为这些缺陷可能早于精神病的发病，我们相信我们的策略可能为早期发现和早期干预提供工具，可能导致精神分裂症风险受试者的精神病预防。我们预计我们的研究策略可能为研究和解决精神分裂症患者对尼古丁依赖的脆弱性增加提供新的方法。

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.