Abstract
BackgroundMajor depressive disorder (MDD) is a leading psychiatric disorder that involves complex abnormal biological functions and neural networks. This study aimed to compare the changes in the network connectivity of different brain tissues under different pathological conditions, analyzed the biological pathways and genes that are significantly related to disease progression, and further predicted the potential therapeutic drug targets.MethodsExpression of differentially expressed genes (DEGs) were analyzed with postmortem cingulate cortex (ACC) and prefrontal cortex (PFC) mRNA expression profile datasets downloaded from the Gene Expression Omnibus (GEO) database, including 76 MDD patients and 76 healthy subjects in ACC and 63 MDD patients and 63 healthy subjects in PFC. The co-expression network construction was based on system network analysis. The function of the genes was annotated by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Human Protein Reference Database (HPRD, http://www.hprd.org/) was used for gene interaction relationship mapping.ResultsWe filtered 586 DEGs in ACC and 616 DEGs in PFC for further analysis. By constructing the co-expression network, we found that the gene connectivity was significantly reduced under disease conditions (P = 0.04 in PFC and P = 1.227e−09 in ACC). Crosstalk analysis showed that CD19, PTDSS2 and NDST2 were significantly differentially expressed in ACC and PFC of MDD patients. Among them, CD19 and PTDSS2 have been targeted by several drugs in the Drugbank database. KEGG pathway analysis demonstrated that the function of CD19 and PTDSS2 were enriched with the pathway of Glycerophospholipid metabolism and T cell receptor signaling pathway.ConclusionCo-expression network and tissue comparing analysis can identify signaling pathways and cross talk genes related to MDD, which may provide novel insight for understanding the molecular mechanisms of MDD.
Highlights
Major depressive disorder (MDD) is a leading psychiatric disorder that involves complex abnormal biological functions and neural networks
586 differentially expressed genes (DEGs) were obtained in anterior cingulate cortex (ACC) (Fig. 1a) and 616 DEGs in prefrontal cortex (PFC) (Fig. 1b)
We found that DEGs in ACC were mainly associated with circulatory system related pathways (Fig. 4a), while DEGs in PFC were enriched in metabolic system related pathways (Fig. 4b)
Summary
Major depressive disorder (MDD) is a leading psychiatric disorder that involves complex abnormal biological functions and neural networks. This study aimed to compare the changes in the network connectivity of different brain tissues under different pathological conditions, analyzed the biological pathways and genes that are significantly related to disease progression, and further predicted the potential therapeutic drug targets. In recent years, accumulating evidence suggests that depression is caused by a single brain region or a single gene abnormality but a disease with complex genetic characteristics and multiple etiologies. Widespread brain areas associated with “emotional network” were found to be abnormal in structure, function, and coordinated activity in MDD. Disturbances in brain activity and impaired mood regulation are considered to be the main neuropathology underlying depression [8]. Depression is a heterogeneous syndrome with distinct causes and pathophysiology
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