Convergent molecular, cellular, and cortical neuroimaging signatures of major depressive disorder

作者：Kevin Anderson, Meghan A. Collins, Ru Kong, Kacey Fang, Jingwei Li, Tong He, Adam M. Chekroud, B.T. Thomas Yeo, Avram J. Holmes · 发表于：Proceedings of the National Academy of Sciences · 年份：2020 · DOI：10.1073/pnas.2008004117 · 被引用次数：184 · 研究领域：Functional Brain Connectivity Studies、Tryptophan and brain disorders、Treatment of Major Depression

≥ 23,723). Integrative analyses incorporate measures of cortical gene expression, postmortem patient transcriptional data, depression genome-wide association study (GWAS), and single-cell gene transcription. Neuroimaging correlates of depression and negative affect were consistent across three independent datasets. Linking ex vivo gene down-regulation with in vivo neuroimaging, we find that transcriptional correlates of depression imaging phenotypes track gene down-regulation in postmortem cortical samples of patients with depression. Integrated analysis of single-cell and Allen Human Brain Atlas expression data reveal somatostatin interneurons and astrocytes to be consistent cell associates of depression, through both in vivo imaging and ex vivo cortical gene dysregulation. Providing converging evidence for these observations, GWAS-derived polygenic risk for depression was enriched for genes expressed in interneurons, but not glia. Underscoring the translational potential of multiscale approaches, the transcriptional correlates of depression-linked brain function and structure were enriched for disorder-relevant molecular pathways. These findings bridge levels to connect specific genes, cell classes, and biological pathways to in vivo imaging correlates of depression.