Clinical and Molecular Genetics of Psychotic Depression
Clinical and Molecular Genetics of Psychotic Depression
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DOI：
10.1093/schbul/sbt040
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发表时间：
2013-07-01
影响因子：
6.6
通讯作者：
Domschke, Katharina
中科院分区：
文献类型：
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作者：
Domschke, Katharina
这篇综述提供了关于“精神病性抑郁症”临床表型的临床和分子遗传学以及药物遗传学研究的全面概述。关于情感障碍和精神障碍的范畴和维度疾病模型的长期争论的结果被讨论，从单相抑郁到双相情感障碍和分裂情感障碍到精神分裂症。临床遗传学研究表明，精神病性抑郁具有家族聚集性和相当大的遗传性(39%)，部分与分裂情感障碍、精神分裂症和情感障碍共享。分子遗传学研究指出，精神病性抑郁的潜在危险基因与分裂情感障碍(1q42、22q11、19p13)、抑郁症、双相情感障碍和精神分裂症(6p、8p22、10p13-12、10p14、13q13-14、13q32、18p、22q11-13)以及几个易感基因(如BDNF、DBH、DTNBP1、DRD2、DRD4、GSK-3β、MAO-A)相同。药物遗传学研究表明，5-HTT、TPH1和DTNBP1基因变异在精神病抑郁症的抗抑郁治疗反应中起中介作用。遗传因素被认为是精神病抑郁的疾病风险的一部分，沿着情感-精神病谱系与障碍部分重叠。因此，专注于精神性抑郁症的基因研究可能会激发出一种更多维度的、神经生物学的和以症状为导向的情感和精神障碍分类，挑战克拉佩尔的二分法观点。此外，药物遗传学研究可能有助于开发一种更个性化的治疗精神病抑郁的方法，根据基因类型定制抗抑郁/抗精神病药物治疗。
This review provides a comprehensive overview of clinical and molecular genetic as well as pharmacogenetic studies regarding the clinical phenotype of "psychotic depression." Results are discussed with regard to the long-standing debate on categorical vs dimensional disease models of affective and psychotic disorders on a continuum from unipolar depression over bipolar disorder and schizoaffective disorder to schizophrenia. Clinical genetic studies suggest a familial aggregation and a considerable heritability (39%) of psychotic depression partly shared with schizoaffective disorder, schizophrenia, and affective disorders. Molecular genetic studies point to potential risk loci of psychotic depression shared with schizoaffective disorder (1q42, 22q11, 19p13), depression, bipolar disorder, and schizophrenia (6p, 8p22, 10p13-12, 10p14, 13q13-14, 13q32, 18p, 22q11-13) and several vulnerability genes possibly contributing to an increased risk of psychotic symptoms in depression (eg, BDNF, DBH, DTNBP1, DRD2, DRD4, GSK-3beta, MAO-A). Pharmacogenetic studies implicate 5-HTT, TPH1, and DTNBP1 gene variation in the mediation of antidepressant treatment response in psychotic depression. Genetic factors are suggested to contribute to the disease risk of psychotic depression in partial overlap with disorders along the affective-psychotic spectrum. Thus, genetic research focusing on psychotic depression might inspire a more dimensional, neurobiologically and symptom-oriented taxonomy of affective and psychotic disorders challenging the dichotomous Kraepelinian view. Additionally, pharmacogenetic studies might aid in the development of a more personalized treatment of psychotic depression with an individually tailored antidepressive/antipsychotic pharmacotherapy according to genotype.