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T helper-1 activation via interleukin-16 is a key phenomenon in the acute phase of severe, first-episode major depressive disorder and suicidal behaviors

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机构： [1]Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand [2]Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf, Iraq [3]Research Group of Organic Synthesis and Catalysis, University of Pannonia, Egyetem u. 10, 8200 Veszprém, Hungary [4]Cognitive Impairment and Dementia Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand [5]Department of Chemistry, College of Science, University of Kufa, Kufa, Iraq [6]Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria [7]Research Institute, Medical University Plovdiv, Plovdiv, Bulgaria [8]Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea [9]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 [10]Key Laboratory of Psychosomatic Medicine, Chinese Academy of Medical Sciences, Chengdu, 610072, China

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关键词： Neuro-immune Inflammation Cytokines Mood disorders

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Immune-inflammatory pathways in major depressive disorder are confined to the major dysmood disorder (MDMD) phenotype (Maes et al., 2022). No studies have addressed the immune profile of first episode MDMD (FE-MDMD).This study investigated the immune profiles of 71 patients with the acute phase of first-episode major depressive disorder (FE-MDMD) and 40 healthy controls. We measured 48 cytokines/chemokines/growth factors, classical M1, alternative M2, T helper (Th)-1, Th-2, and Th-17 phenotypes, immune-inflammatory response system (IRS), compensatory immunoregulatory system (CIRS), and neuro-immunotoxicity profiles.FE-MDMD patients show significantly activated M1, M2, Th-1, IRS, CIRS, and neurotoxicity, but not Th-2 or Th-17, profiles compared to controls. FE-MDMD is accompanied by Th-1 polarization, while there are no changes in M1/M2 or IRS/CIRS ratios. The top single indicator of FE-MDMD was by far interleukin (IL)-16, followed at a distance by TRAIL, IL-2R, tumor necrosis factor (TNF)-β. The severity of depression and anxiety was strongly associated with IRS (positively) and Th-2 (inversely) profiles, whereas suicidal behavior was associated with M1 activation. Around 56-60% of the variance in depression, anxiety, and suicidal behavior scores was explained by IL-16, platelet-derived growth factor (PDGF) (both positively), and IL-1 receptor antagonist (inversely). Increased neurotoxicity is mainly driven by IL-16, TNF-α, TRAIL, IL-6, and chemokine (CCL2, CCL11, CXCL1, CXCL10) signaling. Antidepressant-treated patients show an increased IRS/CIRS ratio as compared with drug-naïve FE-MDMD patients.FE-MDMD is accompanied by positive regulation of the IRS mainly driven by Th-1 polarization and T cell activation (via binding of IL-16 to CD4), and TNF, chemokine, and growth factor signaling.Copyright © 2023. Production and hosting by Elsevier B.V.

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Q1 MULTIDISCIPLINARY SCIENCES

影响因子： 11.4 最新[2023版] 11 最新五年平均 11.4 出版当年[2023版] 0 出版当年五年平均 11.4 出版前一年[2023版]

第一作者：

第一作者机构： [1]Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand [2]Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf, Iraq

通讯作者：

通讯机构： [1]Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand [4]Cognitive Impairment and Dementia Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand [6]Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria [7]Research Institute, Medical University Plovdiv, Plovdiv, Bulgaria [8]Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea [9]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 [10]Key Laboratory of Psychosomatic Medicine, Chinese Academy of Medical Sciences, Chengdu, 610072, China [*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.

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T helper-1 activation via interleukin-16 is a key phenomenon in the acute phase of severe, first-episode major depressive disorder and suicidal behaviors