Neuropeptides as the Shared Genetic Crosstalks Linking Periodontitis and Major Depression Disorder.

Background: The aim of this study was at investigating the association between major depressive disorder (MDD) and periodontitis based on crosstalk genes and neuropeptides.

Methods: Datasets for periodontitis (GSE10334, GSE16134, and GSE23586) and MDD (GSE38206 and GSE39653) were downloaded from GEO. Following batch correction, a differential expression analysis was applied (MDD: ∣log2FC | >0 and periodontitis ∣log2FC | ≥0.5, < 0.05). The neuropeptide data were downloaded from NeuroPep and NeuroPedia. Intersected genes were potential crosstalk genes. The correlation between neuropeptides and crosstalk genes in MDD and periodontitis was analyzed with Pearson correlation coefficient. Subsequently, regression analysis was performed to calculate the differentially regulated link. Cytoscape was used to map the pathways of crosstalk genes and neuropeptides and to construct the protein-protein interaction network. Lasso regression was applied to screen neuropeptides, whereby boxplots were created, and receiver operating curve (ROC) analysis was conducted.

Results: The MDD dataset contained 30 case and 33 control samples, and the periodontitis dataset contained 430 case and 139 control samples. 35 crosstalk genes were obtained. A total of 102 neuropeptides were extracted from the database, which were not differentially expressed in MDD and periodontitis and had no intersection with crosstalk genes. Through lasso regression, 9 neuropeptides in MDD and 43 neuropeptides in periodontitis were obtained. Four intersected neuropeptide genes were obtained, i.e., ADM, IGF2, PDYN, and RETN. The results of ROC analysis showed that IGF2 was highly predictive in MDD and periodontitis. ADM was better than the other three genes in predicting MDD disease. A total of 13 crosstalk genes were differentially coexpressed with four neuropeptides, whereby FOSB was highly expressed in MDD and periodontitis.

Conclusion: The neuropeptide genes ADM, IGF2, PDYN, and RETN were intersected between periodontitis and MDD, and FOSB was a crosstalk gene related to these neuropeptides on the transcriptomic level. These results are a basis for future research in the field, needing further validation.