Deconstructing schizophrenia: An overview of the use of endophenotypes in order to understand a complex disorder
Deconstructing schizophrenia: An overview of the use of endophenotypes in order to understand a complex disorder
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DOI：
10.1093/schbul/sbl049
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发表时间：
2007-01-01
影响因子：
6.6
通讯作者：
Gottesman, Irving I.
中科院分区：
文献类型：
--
作者：
Braff, David L.;Freedman, Robert;Gottesman, Irving I.
精神分裂症的遗传学研究已经采用了多种方法。一个新兴的策略是使用内表型，以了解和确定遗传传递的功能重要性，脑为基础的赤字在精神分裂症kinetics。内表型策略是本期《精神分裂症通报》的一个主题。内表型是定量的、可遗传的、性状相关的缺陷，通常通过基于实验室的方法而不是临床观察来评估。内表型被认为比精神分裂症的临床症状更接近遗传变异，因此与遗传风险因素密切相关。精神病神经科学家使用内表型策略来了解精神分裂症的遗传基础，这给他们提供了广泛的机会。在这种情况下，遗传变异，如单核苷酸多态性（SNP）诱导异常的内表型域，如神经认知，神经发育，代谢和神经生理学。本文讨论了精神分裂症的遗传学研究中存在的挑战，包括确定、上位性、种族多样性以及第二代抗精神病药物对神经认知和神经生理学指标的潜在正常化作用。应对这些挑战的强有力的战略将在本期评论和后续文章中讨论。本文总结了概念上的进步和进展，在精神分裂症的内在表型的测量和使用的基础上，精神分裂症的遗传学的多站点国家精神卫生协会。内表型策略提供了强大的和令人兴奋的机会，了解遗传赋予的神经生物学脆弱性和可能的新的强有力的推理和基于分子的治疗精神分裂症。
The genetics of schizophrenia has been approached utilizing a variety of methods. One emerging strategy is the use of endophenotypes in order to understand and identify the functional importance of genetically transmitted, brain-based deficits across schizophrenia kindreds. The endophenotype strategy is a topic of this issue of Schizophrenia Bulletin. Endophenotypes are quantitative, heritable, trait-related deficits typically assessed by laboratory-based methods rather than clinical observation. Endophenotypes are seen as closer to genetic variation than are clinical symptoms of schizophrenia, and are therefore closely linked to heritable risk factors. There has been a broad expansion of opportunities available to psychiatric neuroscientists who use the endophenotype strategy to understand the genetic basis of schizophrenia. In this context, genetic variation such as single nucleotide polymorphisms (SNPs) induces abnormalities in endophenotypic domains such as neurocognition, neurodevelopment, metabolism, and neurophysiology. This article discusses the challenges that abound in genetic research of schizophrenia, including issues in ascertainment, epistasis, ethnic diversity, and the potentially normalizing effects of second-generation antipsychotic medications on neurocognitive and neurophysiological measures. Robust strategies for meeting these challenges are discussed in this review and the subsequent articles in this issue. This article summarizes conceptual advances and progress in the measurement and use of endophenotypes in schizophrenia that form the basis of the multisite National Institute of Mental Health Consortium on the Genetics of Schizophrenia. The endophenotype strategy offers powerful and exciting opportunities to understand the genetically conferred neurobiological vulnerabilities and possible new strong inference and molecularly based treatments for schizophrenia.