Psychosis Genetics: Modeling the Relationship Between Schizophrenia, Bipolar Disorder, and Mixed (or "Schizoaffective") Psychoses
Psychosis Genetics: Modeling the Relationship Between Schizophrenia, Bipolar Disorder, and Mixed (or "Schizoaffective") Psychoses
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DOI：
10.1093/schbul/sbp020
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发表时间：
2009-05-01
影响因子：
6.6
通讯作者：
Owen, M. J.
中科院分区：
文献类型：
--
作者：
Craddock, Nick;O'Donovan, M. C.;Owen, M. J.
由于技术的改进和样本量的大大增加，过去两年在鉴定精神病学表型的特定遗传风险因素方面取得了前所未有的进展。据报道，双相情感障碍中ANK3和CACNA1C的常见多态性以及精神分裂症中ZNF804A的常见多态性具有很强的遗传关联，GABA(a)受体基因的常见变异与双相情感障碍和精神分裂症的特征之间存在相对特定的关联。此外，与对照组相比，精神分裂症患者中罕见拷贝数变异（CNVs）的发生率有所增加。这些新出现的数据为探索精神病学表型之间的关系提供了强大的资源，可以而且应该用于精神病学的概念化、分类和诊断。已经很清楚的是，一般来说，遗传关联并不特定于某一传统诊断类别。例如，ZNF804A的变异与双相情感障碍和精神分裂症的风险相关，一些罕见的CNVs与自闭症、癫痫以及精神分裂症的风险相关。这些数据与功能性精神病的简单二分模型不一致，表明迫切需要朝着(a)更好地代表临床人群中所见的表型变异范围和(b)反映导致表型的潜在生物学变异的方法发展。我们考虑精神病模型的含义以及认识和研究具有突出情感和精神病特征的疾病的重要性。我们得出的结论是，如果精神病学要转化新研究方法提供的机会，我们必须最终放弃19世纪的二分法，转向适合21世纪的分类方法。
As a result of improving technologies and greatly increased sample sizes, the last 2 years has seen unprecedented advances in identification of specific genetic risk factors for psychiatric phenotypes. Strong genetic associations have been reported at common polymorphisms within ANK3 and CACNA1C in bipolar disorder and ZNF804A in schizophrenia and a relatively specific association between common variation in GABA(A) receptor genes and cases with features of both bipolar disorder and schizophrenia. Further, the occurrence of rare copy number variants (CNVs) has been shown to be increased in schizophrenia compared with controls. These emerging data provide a powerful resource for exploring the relationship between psychiatric phenotypes and can, and should, be used to inform conceptualization, classification, and diagnosis in psychiatry. It is already clear that, in general, genetic associations are not specific to one of the traditional diagnostic categories. For example, variation at ZNF804A is associated with risk of both bipolar disorder and schizophrenia, and some rare CNVs are associated with risk of autism and epilepsy as well as schizophrenia. These data are not consistent with a simple dichotomous model of functional psychosis and indicate the urgent need for moves toward approaches that (a) better represent the range of phenotypic variation seen in the clinical population and (b) reflect the underlying biological variation that gives rise to the phenotypes. We consider the implications for models of psychosis and the importance of recognizing and studying illness that has prominent affective and psychotic features. We conclude that if psychiatry is to translate the opportunities offered by new research methodologies, we must finally abandon a 19th-century dichotomy and move to a classificatory approach that is worthy of the 21st century.