背景:尽管在确定抑郁症的遗传风险因素方面取得了显著成功,关于某些疾病表型的确切遗传机制仍然存在悬而未决的问题,比如大脑结构和功能的损伤。
方法:进行了综合多模态神经影像学荟萃分析,以检查初发药物的重度抑郁障碍(DF-MDD)患者的大脑结构和功能变化。结合艾伦人脑图集,进行转录组-神经成像空间关联分析以鉴定其表达与这些脑结构和功能变化相关的基因。接下来是一系列基因功能标签分析。
结果:Meta分析显示脑岛灰质萎缩,颞极,小脑和中央后回,和复杂的时空极超功能和阴囊/前突功能低下的模式,DF-MDD中的角回和舌回。此外,这些大脑结构和功能的变化在空间上与1194和1733基因的表达相关,分别。重要的是,这两个基因集及其功能特征包括功能富集,具体表达,行为相关性,构建蛋白质-蛋白质相互作用网络。
结论:结果值得使用大样本DF-MDD进一步验证。
结论:我们的发现不仅证实了抑郁症的多基因性质,但也提示了这种疾病中大脑结构和功能损伤的常见和不同的遗传调制。
Despite remarkable success in identifying genetic risk factors for depression, there are still open questions about the exact genetic mechanisms underlying certain disease phenotypes, such as brain structural and functional impairments.
Comprehensive multi-modal neuroimaging meta-analyses were conducted to examine changes in brain structure and function in drug-naive first-episode patients with major depressive disorder (DF-MDD). Combined with the Allen Human Brain Atlas, transcriptome-neuroimaging spatial association analyses were performed to identify genes whose expression related to these brain structural and functional changes, followed by a range of gene functional signature analyses.
Meta-analyses revealed gray matter atrophy in the insula, temporal pole, cerebellum and postcentral gyrus, and a complex pattern of hyper-function in the temporal pole and hypo-function in the cuneus/precuneus, angular gyrus and lingual gyrus in DF-MDD. Moreover, these brain structural and functional changes were spatially associated with the expression of 1194 and 1733 genes, respectively. Importantly, there were commonalities and differences in the two gene sets and their functional signatures including functional enrichment, specific expression, behavioral relevance, and constructed protein-protein interaction networks.
The results merit further verification using a large sample of DF-MDD.
Our findings not only corroborate the polygenic nature of depression, but also suggest common and distinct genetic modulations of brain structural and functional impairments in this disorder.