Opposite Molecular Signatures of Depression in Men and Women.
Opposite Molecular Signatures of Depression in Men and Women.
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男性和女性抑郁症的分子特征相反。
DOI：
10.1016/j.biopsych.2018.01.017
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发表时间：
2018-07-01
影响因子：
10.6
通讯作者：
Sibille E
中科院分区：
文献类型：
--
作者：
Seney ML;Huo Z;Cahill K;French L;Puralewski R;Zhang J;Logan RW;Tseng G;Lewis DA;Sibille E
重度抑郁症 (MDD) 影响女性的频率大约是男性的两倍。女性患非典型抑郁症、嗜睡和体重增加的可能性是女性的三倍。这表明 MDD 的分子机制可能因性别而异。为了检验这一假设，我们对三个皮质边缘脑区、背外侧前额叶皮层、膝下前扣带皮层和基底外侧杏仁核进行了大规模基因表达荟萃分析（N=26 名男性、24 名患有 MDD 的女性和性别匹配的对照）。使用无阈值方法、基因本体论和细胞类型特异性分析进一步分析结果。使用单独的数据集进行独立验证 [N=13 MDD 受试者/性别； 22 名对照（13 名男性，9 名女性）]。在患有 MDD 的男性中差异表达的 706 个基因和患有 MDD 的女性中差异表达的 882 个基因中，只有 21 个基因在两性中发生相同方向的变化。值得注意的是，患有重度抑郁症的男性和女性之间有 52 个基因表现出相反方向的表达变化。使用无阈值方法获得了类似的结果，其中男性和女性的 MDD 总体转录谱相反。基因本体论表明，患有 MDD 的男性突触相关基因减少，而患有 MDD 的女性则表现出该通路的转录增加。细胞类型特异性分析表明，患有MDD的男性少突胶质细胞和小胶质细胞相关基因增加，而患有MDD的女性这些细胞类型的标记物减少。 MDD 的大脑转录谱因性别而异，患有 MDD 的男性和女性之间存在多种相反方向的转录变化。
Major depressive disorder (MDD) affects women approximately twice as often as men. Women are three times as likely to have atypical depression, with hypersomnia and weight gain. This suggests that the molecular mechanisms of MDD may differ by sex. To test this hypothesis, we performed a large-scale gene expression meta-analysis across three corticolimbic brain regions, the dorsolateral prefrontal cortex, subgenual anterior cingulate cortex, and basolateral amygdala (N=26 men, 24 women with MDD and sex-matched controls). Results were further analyzed using a threshold-free approach, gene ontology, and cell type-specific analyses. A separate dataset was used for independent validation [N=13 MDD subjects/sex; 22 controls (13 males, 9 females)]. Of the 706 genes differentially expressed in men with MDD and 882 genes differentially expressed in women with MDD, only 21 were changed in the same direction in both sexes. Notably, 52 genes displayed expression changes in opposite directions between men and women with MDD. Similar results were obtained using a threshold-free approach, where the overall transcriptional profile of MDD was opposite in men and women. Gene ontology indicated that men with MDD had decreases in synapse-related genes, whereas women with MDD exhibited transcriptional increases in this pathway. Cell type-specific analysis indicated that men with MDD exhibited increases in oligodendrocyte- and microglia-related genes, while women with MDD had decreases in markers of these cell types. The brain transcriptional profile of MDD differs greatly by sex, with multiple transcriptional changes in opposite directions between men and women with MDD.
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DOI：
10.1073/pnas.1507125112
发表时间：
2015-06-09
影响因子：
11.1
作者：
Darmanis S;Sloan SA;Zhang Y;Enge M;Caneda C;Shuer LM;Hayden Gephart MG;Barres BA;Quake SR
通讯作者：
Quake SR
影响因子：
11
作者：
Gray, A. L.;Hyde, T. M.;Sodhi, M. S.
通讯作者：
Sodhi, M. S.
影响因子：
6.6
作者：
KESSLER, RC;MCGONAGLE, KA;BLAZER, DG
通讯作者：
BLAZER, DG
影响因子：
11.3
作者：
BRESLAU, N;SCHULTZ, L;PETERSON, E
通讯作者：
PETERSON, E
影响因子：
11.3
作者：
Benazzi, F
通讯作者：
Benazzi, F