Comparative analysis of hippocampal transcriptional features between major depressive disorder patients and animal models

Background: Major depressive disorder (MDD) is a psychiatric disorder caused by various etiologies. Chronic stress models are used to simulate the heterogeneous pathogenic processes of depression. However, few studies have compared transcriptional features between stress models and MDD patients. Methods: We generated hippocampal transcriptional profiles of the chronic social defeat model by RNA sequencing and downloaded raw data of the same brain region from public databases of the chronic unpredictable mild stress model, the learned helplessness model, and MDD patients. Differential expression and gene co-expression analyses were integrated to compare transcriptional features between stress models and MDD patients. Results: Each stress model shared 11.4% to 16.3% of differentially expressed genes with MDD patients. Functional analysis at the gene expression level identified altered ensheathment of neurons in both stress models and MDD patients. At the gene network level, each stress model shared 20.9% to 41.6% of co-expressed genes with MDD patients. Functional analysis based on these genes found that axon guidance signaling is the most significantly enriched pathway that was shared by all stress models and MDD patients. Limitations: This study was limited by considering only a single brain region and a single sex of stress model animals. Conclusions: Our results show that hippocampal transcriptional features of stress models partially overlap with those of MDD patients. The canonical pathways of MDD patients, including ensheathment of neurons, PTEN signaling, and axonal guidance signaling, were shared with all stress models. Our findings provide further clues to understand the molecular mechanisms of depression.