Background: Depression is the most common comorbidities associated with rheumatoid arthritis (RA). We aimed to explore the mechanism of association between RA and depression.
Methods: 120 subjects were enrolled and depression was diagnosed and assessed using DSM-5 and 24-item version of Hamilton Depression Scale. Pain intensity and joint function in patients with RA were assessed using the visual analog scale (VAS) and health assessment questionnaire (HAQ). Serum levels of interferon-gamma (IFN-γ), indoleamine 2,3-dioxygenase (IDO), kynurenine (KYN), tryptophan (TRP), and quinolinic acid (QUIN)were detected. In animal experiments, K/BxN mice with RA-like phenotype was used and depressive behavior was observed. The protein expression level of N-methyl -D- aspartate receptor 2B (NR2B) in the hippocampus was detected.
Results: In this study, 36.67 % of patients with RA also had depression. The working status, month family income, tender joint count, the VAS and HAQ score were the main factors influencing the depression in RA patients. HAQ score was found to be an independent risk factor for depression in RA. Serum IDO, IFN-γ, KYN were increased and TRP contents were decreased in RA group. K/BxN mice with RA-like phenotype showed depressive behavior. However, injection of IFN-γ neutralizing antibody could inhibit kynurenine pathway and reverse the depressive behavior in mice. The levels of QUIN in the neurotoxic metabolic pathway were increased and N-methyl -D- aspartate receptors (NMDAR) were activated, which may be the mechanism behind the onset of depression.
Conclusions: From clinical and preclinical aspects, the occurrence of depression in RA was explored and the related mechanism was revealed.
Keywords: Depression; Interferon-gamma; Rheumatoid arthritis; Tryptophan–kynurenine pathway.
Copyright © 2022 Elsevier B.V. All rights reserved.