Major depressive disorder, neuroticism, suicidal behaviors, and depression severity are associated with cytokine networks and their intricate interactions with metabolic syndrome

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

doi:10.1016/j.jpsychores.2024.111951

Major depressive disorder, neuroticism, suicidal behaviors, and depression severity are associated with cytokine networks and their intricate interactions with metabolic syndrome

J Psychosom Res. 2024 Dec:187:111951. doi: 10.1016/j.jpsychores.2024.111951. Epub 2024 Oct 10.

Authors

Michael Maes¹, Ketsupar Jirakran², Asara Vasupanrajit³, 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, 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.
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; Center of Excellence for Maximizing Children's Developmental Potential, Department of Pediatric, 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.
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. Electronic address: tonyac7721@163.com.
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. Electronic address: chavit.t@chula.ac.th.
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: 39413534
DOI: 10.1016/j.jpsychores.2024.111951

Abstract

Objectives: To identify alterations in the immune profiles in outpatients with major depression (MDD), and its associations with key features, such as suicidal ideation, neuroticism, cognitive symptoms, and the depression phenome while accounting for metabolic syndrome (MetS).

Methods: In this case-control study, we assayed 48 serum cytokines, chemokines, and growth factors in 67 healthy controls and 66 MDD outpatients. Around 50 % of the outpatient MDD and control participants had a diagnosis of MetS.

Results: Ten differentially expressed proteins (DEPs) were upregulated in outpatient MDD (i.e., CXCL12, tumor necrosis factor [TNF]β, platelet-derived growth factor [PDGF], CCL11, interleukins [IL]9, IL4, CCL5, CCL2, CCL4, IL1 receptor antagonist [IL1RN]), indicating an immune and defense response. Six DEPs were downregulated (vascular endothelial growth factor A [VEGFA], IL12, CCL3, colony stimulating factor [CSF]1, IL1B, nerve growth factor [NGF]), indicating lowered neurogenesis and neuron death regulation. Significant interactions between outpatient MDD and MetS caused a) substantial increases in IL4, IL17, TNF, TNFB, CCL2, CCL5, PDGF, IL1RN; and b) downregulation of VEGFA and FGF. A large part of the variance in neuroticism (26 %), suicidal behaviors (23 %), and the MDD phenome (31 %) was predicted by immunological data and interactions between MetS and CCL5, TNFB or VEGFA.

Conclusion: Outpatient MDD is characterized by a cytokine profile with neurotoxic potential which partly explains neuroticism, suicidal behaviors, and the phenome's severity. Lowered IL-10 and activated cytokine profiles with neurotoxic potential are characteristics of outpatient MDD and other depression phenotypes, including severe first-episode inpatient MDD. The presence of MetS in outpatient MDD considerably activates immune profiles with neurotoxic potential. Consequently, immune studies in MDD should always be performed in subjects with and without MetS.

Keywords: Cytokines; Depressive spectrum; Inflammation; Major depression; Mood disorders; Neuroimmune.

MeSH terms

Adult
Case-Control Studies
Cytokines* / blood
Depressive Disorder, Major* / blood
Depressive Disorder, Major* / immunology
Female
Humans
Male
Metabolic Syndrome* / blood
Metabolic Syndrome* / immunology
Middle Aged
Neuroticism*
Suicidal Ideation

Substances

Cytokines