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Article

Adverse Childhood Experiences Predict the Phenome of Affective Disorders and These Effects Are Mediated by Staging, Neuroimmunotoxic and Growth Factor Profiles

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Department of Psychiatry, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University and The Thai Red Cross Society, Bangkok 10330, Thailand
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IMPACT Strategic Research Center, Barwon Health, Geelong 3220, Australia
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Department of Psychiatry, Medical University of Plovdiv, 4000 Plovdiv, Bulgaria
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Maximizing Thai Children’s Developmental Potential Research Unit, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
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Center of Excellence in Immunology and Immune-Mediated Diseases, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
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Division of Immunology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
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Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore 560 029, India
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Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Poland
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Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf 54001, Iraq
*
Author to whom correspondence should be addressed.
Academic Editor: Markus Fendt
Cells 2022, 11(9), 1564; https://doi.org/10.3390/cells11091564
Received: 30 March 2022 / Revised: 24 April 2022 / Accepted: 2 May 2022 / Published: 7 May 2022
Adverse childhood experiences (ACEs) enhance pro-inflammatory and pro-oxidant responses. In affective disorders, recent precision nomothetic psychiatry studies disclosed new pathway phenotypes, including an ROI—reoccurrence of illness (ROI)—oxidative stress latent construct. The aim of the present study is to delineate a) whether ACEs sensitize the M1 macrophage, the T helper cells (Th)1, Th2, and Th17, the IRS (immune-inflammatory-responses system), the CIRS (compensatory immunoregulatory system), and the neuroimmunotoxic and growth factor (GF) profiles and whether they are associated with ROI and the phenome of affective disorders and b) the molecular pathways underpinning the effects of the ACEs. We collected supernatants of stimulated (5 μg/mL of PHA and 25 μg/mL of LPS) and unstimulated diluted whole blood in 20 healthy controls and 30 depressed patients and measured a panel of 27 cytokines/GF using a Luminex method. ACEs (comprising mental and physical trauma, mental neglect, domestic violence, family history of mental disease, and parent loss) are accompanied by the increased stimulated, but not unstimulated, production of M1, Th1, Th2, Th17, IRS, neuroimmunotoxic, and GF profiles and are strongly correlated with ROI and the phenome. A latent vector extracted from the ROI features (recurrent episodes and suicidal behaviors) and the IRS/neuroimmunotoxic/GF profiles explains 66.8% of the variance in the phenome and completely mediates the effects of ACEs on the phenome. Enrichment analysis showed that the ACE-associated sensitization of immune/GF profiles involves JAK-STAT, nuclear factor-κB, tumor necrosis factor-α, G-protein coupled receptor, PI3K/Akt/RAS/MAPK, and hypoxia signaling. In summary, the ACE-induced sensitization of immune pathways and secondary immune hits predicts the phenome of affective disorders. View Full-Text
Keywords: early lifetime trauma; depression; mood disorders; inflammation; neuroimmune; cytokines; psychiatry early lifetime trauma; depression; mood disorders; inflammation; neuroimmune; cytokines; psychiatry
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MDPI and ACS Style

Maes, M.; Rachayon, M.; Jirakran, K.; Sodsai, P.; Klinchanhom, S.; Debnath, M.; Basta-Kaim, A.; Kubera, M.; Almulla, A.F.; Sughondhabirom, A. Adverse Childhood Experiences Predict the Phenome of Affective Disorders and These Effects Are Mediated by Staging, Neuroimmunotoxic and Growth Factor Profiles. Cells 2022, 11, 1564. https://doi.org/10.3390/cells11091564

AMA Style

Maes M, Rachayon M, Jirakran K, Sodsai P, Klinchanhom S, Debnath M, Basta-Kaim A, Kubera M, Almulla AF, Sughondhabirom A. Adverse Childhood Experiences Predict the Phenome of Affective Disorders and These Effects Are Mediated by Staging, Neuroimmunotoxic and Growth Factor Profiles. Cells. 2022; 11(9):1564. https://doi.org/10.3390/cells11091564

Chicago/Turabian Style

Maes, Michael, Muanpetch Rachayon, Ketsupar Jirakran, Pimpayao Sodsai, Siriwan Klinchanhom, Monojit Debnath, Agnieska Basta-Kaim, Marta Kubera, Abbas F. Almulla, and Atapol Sughondhabirom. 2022. "Adverse Childhood Experiences Predict the Phenome of Affective Disorders and These Effects Are Mediated by Staging, Neuroimmunotoxic and Growth Factor Profiles" Cells 11, no. 9: 1564. https://doi.org/10.3390/cells11091564

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