重度抑郁症多脑区基因表达谱分析
摘要
Major depressive disorder (MDD), a polygenic disease resulting from complicated interactions between environmental and genetic factors, is becoming an increasingly serious threat to global public health. Genome-wide gene expression analysis is widely used for psychiatric disorders because of its ability to detect spatio-temporal patterns of gene expression. However, it is difficult to elucidate the molecular mechanism of MDD by methods that analyze brain regions and/or genes individually because activation patterns may differ between brain regions and MDD may be regulated by multiple genes with moderate or weak effects. In this study, we used a strategy that leverages information across multiple brain regions and genes. We performed gene set enrichment analysis of transcriptomics data from different brain regions of MDD patients and health controls in 13 datasets from the Gene Expression Omnibus. Our results show that the neuron markers gene set was significantly down-regulated in the associative striatum, anterior cingulate cortex (ACC), and amygdala, which is consistent with current MDD knowledge. The gene expression of glial cell markers was also altered in MDD patients, but there were no consistent patterns across brain regions or datasets from the same region. Moreover, gender-specific activation patterns of the astrocyte markers and oligodendrocyte markers gene sets were observed in the ACC and amygdala. In a comparative analysis of psychiatric disorders, the neuron markers gene set were also significantly down-regulated in multiple brain regions of patients with bipolar disorder and schizophrenia, although the activation patterns of two glial cell markers gene sets and the choroid plexus markers gene set in these two disorders differed from that of MDD. Our results reveal potential candidate brain regions, gene sets, and genes that are altered in MDD.