Yin-Yang 1, a player regulated systematic inflammatory involved in cognitive impairment of depression

A growing number of clinical and preclinical studies suggest that alterations in peripheral and brain immunal system and followed inflammation are associated with the pathophysiology of depression, also leading to the changes in local glucose metabolism in the brain. Here, we identified Yin-yang 1 (YY1), a transcription factor that has been reported to be closely associated with central and peripheral inflammation. The levels of YY1 and IL-1β were significantly increased in blood samples from depressed individuals, and significantly decreased after treatment with Vortioxetine. Meanwhile, it was found that the level of YY1 in plasma was negatively correlated with visual learning reasoning and problem solving in MDD patients, and positively correlated with the level of IL-1β in plasma. CUMS animals showed depressive-like behavior. Compared with the control group, MicroPET analysis showed that the decrease of glucose metabolism in the hippocampus, entorhinal cortex, amygdala, striatum and mPFC was reversed after treatment. After treatment, these changes were reversed. In conclusion, Our study suggested that YY1-NF-κB - IL-1β inflammatory pathway may play an essential part on both mood changes and cognitive impairment in depression, and may be associated with changes in glucose metabolism in the emotion regulation and cognition related brain regions. These findings provide new evidence for the inflammatory mechanisms of depression. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial ChiCTR1900024858 ### Funding Statement Medical Science and Technology Project of Zhejiang Province (2022RC024) and Natural Science Foundation of Zhejiang Province (LQ20H090010) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by ethics review boards of the First Affiliated Hospital of Zhejiang University School of Medicine. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present work are contained in the manuscript