Major Depressive Disorder in Multiple Sclerosis and Aqp4-Antibody Positive Neuromyelitis Optica Spectrum Disorder: A Cross-Sectional Study on Clinical Correlates in Iranian Patients Publisher Pubmed



Mirmosayyeb O ; Vaheb S ; Yazdan Panah M ; Mohammadifard F ; Aghajanian S ; Shaygannejad V
Source: Journal of Psychosomatic Research Published:2026

Abstract

Background Multiple sclerosis (MS) is a chronic, immune-mediated neuroinflammatory disorder of the central nervous system (CNS). Symptoms of depression are more prevalent among patients with MS (PwMS) compared to both the general population and individuals with other chronic debilitating conditions. Objectives This cross-sectional study aimed to examine the prevalence of major depressive disorder (MDD) in PwMS across different MS subtypes, as well as in patients with Neuromyelitis Optica Spectrum Disorder (NMOSD). Also, it sought to identify various risk factors associated with MDD in these neurodemyelinating diseases. Methods A total of 4759 eligible participants were enrolled, comprising 4460 PwMS diagnosed according to the 2017 revision of the McDonald criteria and 299 patients with aquaporin-4 antibody-positive NMOSD (AQP4-NMOSD) diagnosed based on the 2015 International Panel for NMO Diagnosis (IPND-2015) criteria. MDD was diagnosed using structured psychiatric interviews conducted by board-certified psychiatrists, following the Diagnostic and Statistical Manual of Mental Disorders version 4 (DSM-IV) criteria. Results The overall prevalence of MDD was 12.5%, with rates of 12% in PwMS and 13% in AQP4-NMOSD patients. MDD was more frequent in progressive forms of MS compared to relapsing remitting MS (16.2% vs. 11.5%). Older age, female sex, marital status, lower educational attainment, migraine, thyroid dysfunction, anemia, and higher Expanded Disability Status Scale (EDSS) were univariably associated with MDD. In multivariable analysis, primary progressive MS (PPMS) was significantly associated with MDD in minimally adjusted models (OR = 1.98, 95% CI: 1.27–3.07), while this association was only marginally significant in fully adjusted models (OR = 1.59, 95% CI: 0.98–2.58). Conclusion This study highlights the prevalence of clinically diagnosed MDD in both PwMS and AQP4-NMOSD patients. The findings underscore the relevance of comorbidities such as anemia, hypothyroidism, and migraine, as well as the potential association of PPMS phenotype with MDD in PwMS. © 2026 Elsevier Inc.