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非裔美国人精神分裂症风险研究项目(PAARTNERS):精神分裂症患者家庭神经认知功能障碍和遗传度的证据。

Project among African-Americans to explore risks for schizophrenia (PAARTNERS): evidence for impairment and heritability of neurocognitive functioning in families of schizophrenia patients.

机构信息

Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.

出版信息

Am J Psychiatry. 2010 Apr;167(4):459-72. doi: 10.1176/appi.ajp.2009.08091351. Epub 2010 Mar 1.

Abstract

OBJECTIVE

Neurocognitive impairments in schizophrenia are well replicated and widely regarded as candidate endophenotypes that may facilitate understanding of schizophrenia genetics and pathophysiology. The Project Among African-Americans to Explore Risks for Schizophrenia (PAARTNERS) aims to identify genes underlying liability to schizophrenia. The unprecedented size of its study group (N=1,872), made possible through use of a computerized neurocognitive battery, can help further investigation of the genetics of neurocognition. The current analysis evaluated two characteristics not fully addressed in prior research: 1) heritability of neurocognition in African American families and 2) relationship between neurocognition and psychopathology in families of African American probands with schizophrenia or schizoaffective disorder.

METHOD

Across eight data collection sites, patients with schizophrenia or schizoaffective disorder (N=610), their biological relatives (N=928), and community comparison subjects (N=334) completed a standardized diagnostic evaluation and the computerized neurocognitive battery. Performance accuracy and response time (speed) were measured separately for 10 neurocognitive domains.

RESULTS

The patients with schizophrenia or schizoaffective disorder exhibited less accuracy and speed in most neurocognitive domains than their relatives both with and without other psychiatric disorders, who in turn were more impaired than comparison subjects in most domains. Estimated trait heritability after inclusion of the mean effect of diagnostic status, age, and sex revealed significant heritabilities for most neurocognitive domains, with the highest for accuracy of abstraction/flexibility, verbal memory, face memory, spatial processing, and emotion processing and for speed of attention.

CONCLUSION

Neurocognitive functions in African American families are heritable and associated with schizophrenia. They show potential for gene-mapping studies.

摘要

目的

精神分裂症的神经认知损伤得到了很好的复制,被广泛认为是候选的内表型,可能有助于理解精神分裂症的遗传学和病理生理学。非裔美国人探索精神分裂症风险计划(PAARTNERS)旨在确定导致精神分裂症易感性的基因。其研究组的规模空前(N=1872),通过使用计算机化的神经认知测试,可以帮助进一步研究神经认知的遗传学。目前的分析评估了两个以前的研究中没有充分解决的特征:1)非洲裔美国家庭神经认知的遗传性;2)精神分裂症或分裂情感障碍的非洲裔先证者家庭的神经认知与精神病理学之间的关系。

方法

在八个数据收集地点,精神分裂症或分裂情感障碍患者(N=610)、他们的生物学亲属(N=928)和社区对照组(N=334)完成了标准化的诊断评估和计算机化的神经认知测试。分别测量了 10 个神经认知领域的表现准确性和反应时间(速度)。

结果

精神分裂症或分裂情感障碍患者在大多数神经认知领域的准确性和速度都低于他们有或没有其他精神障碍的亲属,而亲属又比对照组在大多数领域的损伤更严重。在包括诊断状态、年龄和性别的平均效应后,纳入的特征遗传性揭示了大多数神经认知领域存在显著的遗传性,其中抽象/灵活性、言语记忆、面部记忆、空间处理和情绪处理的准确性以及注意力的速度遗传性最高。

结论

非洲裔美国家庭的神经认知功能是遗传性的,与精神分裂症有关。它们显示出基因定位研究的潜力。

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