Major depressive disorder (MDD) has an enormous impact on global disease burden, affecting millions of people worldwide and ranking as a leading cause of disability for almost three decades. Past molecular studies of MDD employed bulk homogenates of postmortem brain tissue, which obscures gene expression changes within individual cell types. Here we used single-nucleus transcriptomics to examine ~80,000 nuclei from the dorsolateral prefrontal cortex of male individuals with MDD (n = 17) and of healthy controls (n = 17). We identified 26 cellular clusters, and over 60% of these showed differential gene expression between groups. We found that the greatest dysregulation occurred in deep layer excitatory neurons and immature oligodendrocyte precursor cells (OPCs), and these contributed almost half (47%) of all changes in gene expression. These results highlight the importance of dissecting cell-type-specific contributions to the disease and offer opportunities to identify new avenues of research and novel targets for treatment.

中文翻译：

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在严重抑郁症中，前额叶皮层的单核转录组学涉及少突胶质细胞前体细胞和兴奋性神经元。

严重抑郁症（MDD）对全球疾病负担产生了巨大影响，影响了全球数百万人，并且已经成为将近三十年来致残的主要原因。过去的MDD分子研究使用了死后脑组织的大量匀浆，这掩盖了单个细胞类型内基因表达的变化。在这里，我们使用单核转录组学检查了患有MDD（n = 17）的男性个体和健康对照组（n = 17）的背外侧前额叶皮层约80,000个核。我们鉴定出26个细胞簇，其中超过60％的簇之间存在差异基因表达。我们发现最大的失调发生在深层兴奋性神经元和不成熟的少突胶质细胞前体细胞（OPC）中，这些几乎占基因表达所有变化的一半（47％）。