Reviewing the genetics of heterogeneity in depression: operationalizations, manifestations and etiologies.
Reviewing the genetics of heterogeneity in depression: operationalizations, manifestations and etiologies.
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回顾抑郁症异质性的遗传学：操作化，表现和病因。
DOI：
10.1093/hmg/ddaa115
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发表时间：
2020-09-30
影响因子：
3.5
通讯作者：
Fried EI
中科院分区：
文献类型：
--
作者：
Cai N;Choi KW;Fried EI
随着抑郁症全基因组关联研究的进展，从2013年在约1.6万人中发现零命中到2020年在100多万人中发现223命中，了解这种使人衰弱的疾病的遗传结构似乎不再是一项不可能完成的任务。现在紧迫的问题是，最近发现的变异是否描述了单一疾病实体的病因学。有无数种方法可以测量和操作抑郁症的严重程度，《精神疾病诊断与统计手册》中定义的重度抑郁症-5仅基于症状特征就可以以超过10,000种方式表现出来。个体和样本之间发育时间、共病和环境背景的差异进一步增加了异质性。随着大数据越来越多地使精神病学中的基因组发现成为可能，现在比以往任何时候都更及时地明确区分基因对“抑郁症”的影响，而不是抑郁症。在这里，我们介绍三个来源的异质性：操作，表现和病因。我们回顾了最近使用临床和数据驱动方法识别抑郁症亚型的努力，研究了不同背景下抑郁症遗传结构的差异，并认为抑郁症操作的异质性可能是不一致的重要来源。最后，我们对该领域的发展提出了建议和考虑。
With progress in genome-wide association studies of depression, from identifying zero hits in ~16 000 individuals in 2013 to 223 hits in more than a million individuals in 2020, understanding the genetic architecture of this debilitating condition no longer appears to be an impossible task. The pressing question now is whether recently discovered variants describe the etiology of a single disease entity. There are a myriad of ways to measure and operationalize depression severity, and major depressive disorder as defined in the Diagnostic and Statistical Manual of Mental Disorders-5 can manifest in more than 10 000 ways based on symptom profiles alone. Variations in developmental timing, comorbidity and environmental contexts across individuals and samples further add to the heterogeneity. With big data increasingly enabling genomic discovery in psychiatry, it is more timely than ever to explicitly disentangle genetic contributions to what is likely ‘depressions’ rather than depression. Here, we introduce three sources of heterogeneity: operationalization, manifestation and etiology. We review recent efforts to identify depression subtypes using clinical and data-driven approaches, examine differences in genetic architecture of depression across contexts, and argue that heterogeneity in operationalizations of depression is likely a considerable source of inconsistency. Finally, we offer recommendations and considerations for the field going forward.
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影响因子：
82.9
作者：
Drysdale AT;Grosenick L;Downar J;Dunlop K;Mansouri F;Meng Y;Fetcho RN;Zebley B;Oathes DJ;Etkin A;Schatzberg AF;Sudheimer K;Keller J;Mayberg HS;Gunning FM;Alexopoulos GS;Fox MD;Pascual-Leone A;Voss HU;Casey BJ;Dubin MJ;Liston C
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作者：
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通讯作者：
Zaitlen, Noah
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作者：
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通讯作者：
Serretti, Alessandro
影响因子：
4.5
作者：
Byrne, Enda M.;Carrillo-Roa, Tania;Wray, Naomi R.
通讯作者：
Wray, Naomi R.
影响因子：
--
作者：
Bierut, LJ;Heath, AC;Martin, NG
通讯作者：
Martin, NG