Adverse childhood experiences and recent negative events are associated with activated immune and growth factor pathways, the phenome of first episode major depression and suicidal behaviors

Abbas F Almulla; Ali Abbas Abo Algon; Michael Maes

doi:10.1016/j.psychres.2024.115812

Adverse childhood experiences and recent negative events are associated with activated immune and growth factor pathways, the phenome of first episode major depression and suicidal behaviors

Psychiatry Res. 2024 Apr:334:115812. doi: 10.1016/j.psychres.2024.115812. Epub 2024 Feb 29.

Authors

Abbas F Almulla¹, Ali Abbas Abo Algon², Michael Maes³

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, and King Chulalongkorn Memorial Hospital, the Thai Red Cross Society, Bangkok, Thailand; Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf, Iraq.
² Research Group of Organic Synthesis and Catalysis, University of Pannonia, Egyetem u. 10, 8200 Veszprém, Hungary.
³ 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, and King Chulalongkorn Memorial Hospital, the Thai Red Cross Society, Bangkok, Thailand; Cognitive Impairment and Dementia Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria; Research Institute, Medical University Plovdiv, Plovdiv, Bulgaria; Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea. Electronic address: dr.michaelmaes@hotmail.com.

PMID: 38442479
DOI: 10.1016/j.psychres.2024.115812

Abstract

This research assessed the effects of adverse childhood experiences (ACEs) and negative life events (NLEs) on forty-eight cytokines/chemokines/growth factors, in 71 FE-MDMD patients and forty heathy controls. ACEs are highly significantly associated with the classical M1 macrophage, T helper (Th)-1, Th-1 polarization, IRS, and neurotoxicity immune profiles, and not with the alternative M2, and Th-2 immune profiles. There are highly significant correlations between ACEs and NLEs and different cytokines/chemokines/growth factors, especially with interleukin (IL)-16, CCL27, stem cell growth factor, and platelet-derived growth factor. Partial Least Squares analysis showed that 62.3 % of the variance in the depression phenome (based on severity of depression, anxiety and suicidal behaviors) was explained by the regression on IL-4 (p = 0.001, inversely), the sum of ACEs + NLEs (p < 0.0001), and a vector extracted from 10 cytokines/chemokines/growth factors (p < 0.0001; both positively associated). The latter partially mediated (p < 0.0001) the effects of ACE + NLEs on the depression phenome. In conclusion, part of the effects of ACEs and NLEs on the depression phenome is mediated via activation of immune and growth factor networks. These pathways have a stronger impact in subjects with lowered activities of the compensatory immune-regulatory system.

Keywords: Affective disorders; Biomarkers; Cytokines; Inflammation; Major depression; Neuro-immune.

MeSH terms

Adverse Childhood Experiences*
Chemokines
Cytokines
Depression
Depressive Disorder, Major* / genetics
Humans
Suicidal Ideation

Substances

Cytokines
Chemokines