Simple dysmood disorder, a mild subtype of major depression, is not an inflammatory condition: Depletion of the compensatory immunoregulatory system

Michael Maes; Asara Vasupanrajit; Ketsupar Jirakran; Bo Zhou; Chavit Tunvirachaisakul; Abbas F Almulla

doi:10.1016/j.jad.2025.01.101

Simple dysmood disorder, a mild subtype of major depression, is not an inflammatory condition: Depletion of the compensatory immunoregulatory system

J Affect Disord. 2025 Jan 21:375:75-85. doi: 10.1016/j.jad.2025.01.101. Online ahead of print.

Authors

Michael Maes¹, Asara Vasupanrajit², Ketsupar Jirakran³, Bo Zhou⁴, Chavit Tunvirachaisakul⁵, Abbas F Almulla⁶

Affiliations

¹ Sichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; Key Laboratory of Psychosomatic Medicine, Chinese Academy of Medical Sciences, Chengdu 610072, China; Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Ph.D. Program in Mental Health, Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Cognitive Impairment and Dementia Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Cognitive Fitness and Biopsychological Technology Research Unit, Faculty of Medicine Chulalongkorn University, Bangkok 10330, Thailand; Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria; Research Institute, Medical University of Plovdiv, Plovdiv, Bulgaria; Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea. Electronic address: dr.michaelmaes@hotmail.com.
² Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Ph.D. Program in Mental Health, Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
³ Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Ph.D. Program in Mental Health, Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Center of Excellence for Maximizing Children's Developmental Potential, Department of Pediatric, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
⁴ Sichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; Key Laboratory of Psychosomatic Medicine, Chinese Academy of Medical Sciences, Chengdu 610072, China.
⁵ Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Ph.D. Program in Mental Health, Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Cognitive Impairment and Dementia Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
⁶ Sichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; Key Laboratory of Psychosomatic Medicine, Chinese Academy of Medical Sciences, Chengdu 610072, China; Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf, Iraq. Electronic address: abbass.chem.almulla1991@gmail.com.

PMID: 39848470
DOI: 10.1016/j.jad.2025.01.101

Abstract

Background: A recent study conducted by the laboratory of the first author revealed that major depression is composed of two distinct subtypes: major dysmood disorder (MDMD) and simple dysmood disorder (SDMD). The latter is a less severe phenotype with fewer aberrant biological pathways. MDMD, but not SDMD, patients were identified to have highly sensitized cytokine/growth factor networks using stimulated whole blood cultures. However, no information regarding serum cytokines/chemokines/growth factors in SDMD is available.

Objectives: This case-control study compares 48 serum cytokines/chemokines/growth factors in academic students with SDMD (n = 64) and first episode (FE)-SDMD (n = 47) to those of control students (n = 44) using a multiplex assay.

Findings: Both FE-SDMD and SDMD exhibited a notable inhibition of immune profiles, such as the compensatory immunoregulatory response system (CIRS) and alternative M2 macrophage and T helper-2 (Th-2) profiles. We observed a substantial reduction in the serum concentrations of five proteins: interleukin (IL)-4, IL-10, soluble IL-2 receptor (sIL-2R), IL-12p40, and macrophage colony-stimulating factor. A considerable proportion of the variability observed in suicidal behaviors (26.7 %) can be accounted for by serum IL-4, IL-10, and sIL-2R (all decreased), CCL11 (eotaxin) and granulocyte CSF (both increased). The same biomarkers (except for IL-10), accounted for 25.5 % of the variance in SDMS severity. A significant correlation exists between decreased levels of IL-4 and elevated ratings of the brooding type of rumination.

Conclusions: SDMD is characterized by the suppression of the CIRS profile, which signifies a disruption of immune homeostasis and tolerance, rather than the presence of an inflammatory response.

Keywords: Affective spectrum; Biomarkers; Growth factors; Inflammation; Mood disorders; Neuro-immune; Suicidal ideation.