Identification of Hub Genes and Potential Mechanisms in Depressive Disorder Aggravated Crohn's Disease

Abstract

Background: The interaction between mental disorders and the gut inflammation has highlighted the potential role of brain-gut interaction in onset, aggravation and recurrence of Crohn’s disease (CD). However, there is little previous study has investigated the molecular mechanisms of the comorbidity of CD and mental disorders. Methods: The GEO database, PHGKB database, GEO2R tool, Metascape, STRING, ImageGP, R program, GeneMANIA website, and EPIC were used to analyse and visualize the results. The clinical-pathological parameters, such as CDEIS, microvilli length of intestine, CRP, IBD evolution time, age at diagnosis, endoscopic activity, GI involvement and the response of anti-TNF therapy were used to identified the hub genes. Findings: ADCYAP1, AVP, CREB1, FKBP5, MAPT, NTSR1, OXTR, PROK2, POMC, ADORA2A, CHRM2, NR1I2, HTR2B, PPARGC1A, TP53, and ADORA1 were detected that had correlations with clinic-pathological parameters, such as CDEIS, microvilli length of intestine, CRP, IBD evolution time, age at diagnosis, endoscopic activity, GI involvement and the response of anti-TNF therapy. In this study, these hub genes, especially CREB1, FKBP5, MAPT, NTSR1, OXTR, PROK2, POMC, HTR2B, and PPARGC1A possibly contribute to the establishment and the deterioration of CD caused by depressive disorder. Among these genes, PROK2 showed the possibility of regulating immune cell (neutrophils and CD4+/ CD8+T cells) infiltration. Interpretation: These hub genes could be further used as potential biomarkers to identify the mental co-morbidities in CD and tailor therapies for individual CD patients. Funding: This study was financially supported by the National Natural Science Foundation of China (81770550) Declaration of Interests: All authors declare that they have no conflict of interest. Ethics Approval Statement: Not applicable.