Inflammation molecular network alterations in a depressive-like primate model

At present, there are no definitive biomarkers for major depressive disorder (MDD). Previous studies prompted that neuroimmunoinflammation is involved in the pathogenesis of depression and its factors become potential diagnostic biomarkers. Non-human primates exhibit depression-like behavior similar to humans in chronically stressed environments. Therefore, in the present study, after completing Whole transcriptome sequencing of peripheral blood, neurology-related and inflammatory molecules in plasma and cerebrospinal fluid were measured by Olink proximity extension assay technology simultaneously in 4 natural depressive-like (DL) cynomolgus monkeys and 4 normal controls to screen potential biological markers. Further, postmortem brain tissues and peripheral blood RNA sequencing data from MDD patients available in the Gene Expression Omnibus (GEO) database were used for cross-species validation. Compared to control monkeys, depressive-like monkeys exhibited elevated levels of neurocan (NCAN). RNA sequencing revealed Toll-like receptor 4 (TLR4) and the interacting S100 calcium-binding protein A family as key molecules in the inflammatory gene network. GEO brain tissue data showed up-regulation of S100A8 and S100A9 in the anterior cingulate cortex of MDD patients. These findings suggest that depressive-like monkeys are in a state of chronic low-grade inflammation and identify NCAN and TLR4 inflammatory network molecules as potential biomarkers of MDD.