Regional gene expression signatures are associated with sex-specific functional connectivity changes in depression.
Regional gene expression signatures are associated with sex-specific functional connectivity changes in depression.
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DOI：
10.1038/s41467-022-32617-1
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发表时间：
2022-09-28
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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作者：
抑郁症的神经基础可能在男性和女性中有所不同，但其潜在机制尚未完全了解。在这里，我们发现，抑郁症与性别特异性模式的异常功能连接的默认模式网络和五个感兴趣的区域与性二态转录效应。在两个独立的数据集中基因表达的区域差异解释了异常连接的神经解剖学分布。这些基因组因性别而异，并且强烈富集了与抑郁症，突触功能，免疫信号和神经发育有关的基因。在一个独立的样本中，我们证实了这一预测，即默认模式网络连接的个体差异可以通过推断的6个抑郁相关基因的大脑表达水平来解释，其中包括PCDH 8，一种与活动相关的突触重组有关的脑特异性原钙粘蛋白整合膜蛋白。总之，我们的研究结果描绘了抑郁症相关功能网络组织中的共享和性别特异性变化，对生物标志物开发和fMRI指导的治疗性神经调节具有影响。抑郁症的神经基础可能因性别而异。在这里，作者表明，抑郁症与男性和女性不同的大脑连接变化有关，这些变化可以通过性别特异性转录组特征来解释，这些特征涉及以前与突触功能，免疫信号和抑郁风险有关的基因。
The neural substrates of depression may differ in men and women, but the underlying mechanisms are incompletely understood. Here, we show that depression is associated with sex-specific patterns of abnormal functional connectivity in the default mode network and in five regions of interest with sexually dimorphic transcriptional effects. Regional differences in gene expression in two independent datasets explained the neuroanatomical distribution of abnormal connectivity. These gene sets varied by sex and were strongly enriched for genes implicated in depression, synapse function, immune signaling, and neurodevelopment. In an independent sample, we confirmed the prediction that individual differences in default mode network connectivity are explained by inferred brain expression levels for six depression-related genes, including PCDH8, a brain-specific protocadherin integral membrane protein implicated in activity-related synaptic reorganization. Together, our results delineate both shared and sex-specific changes in the organization of depression-related functional networks, with implications for biomarker development and fMRI-guided therapeutic neuromodulation. The neural substrates of depression may differ by sex. Here the authors show that depression is associated with distinct brain connectivity changes in men and in women that are explained by sex-specific transcriptomic signatures involving genes previously implicated in synapse function, immune signalling, and depression risk.
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影响因子：
5.7
作者：
Alexander-Bloch AF;Shou H;Liu S;Satterthwaite TD;Glahn DC;Shinohara RT;Vandekar SN;Raznahan A
通讯作者：
Raznahan A
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
DOI：
10.1523/jneurosci.3554-12.2013
发表时间：
2013-02-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Alexander-Bloch A;Raznahan A;Bullmore E;Giedd J
通讯作者：
Giedd J
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
通讯作者：
Liston C
影响因子：
7.7
作者：
Bakker, Nathan;Shahab, Saba;Downar, Jonathan
通讯作者：
Downar, Jonathan