Adverse Childhood Experiences Predict the Phenome of Affective Disorders and These Effects Are Mediated by Staging, Neuroimmunotoxic and Growth Factor Profiles
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 s...
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2022-05-01
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| author | Michael Maes Muanpetch Rachayon Ketsupar Jirakran Pimpayao Sodsai Siriwan Klinchanhom Monojit Debnath Agnieska Basta-Kaim Marta Kubera Abbas F. Almulla Atapol Sughondhabirom |
| author_facet | Michael Maes Muanpetch Rachayon Ketsupar Jirakran Pimpayao Sodsai Siriwan Klinchanhom Monojit Debnath Agnieska Basta-Kaim Marta Kubera Abbas F. Almulla Atapol Sughondhabirom |
| author_sort | Michael Maes |
| collection | DOAJ |
| description | 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. |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T04:16:00Z |
| publishDate | 2022-05-01 |
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| spelling | doaj.art-6bb9c1d898924418a44ad3e61b0304f82023-11-23T08:01:14ZengMDPI AGCells2073-44092022-05-01119156410.3390/cells11091564Adverse Childhood Experiences Predict the Phenome of Affective Disorders and These Effects Are Mediated by Staging, Neuroimmunotoxic and Growth Factor ProfilesMichael Maes0Muanpetch Rachayon1Ketsupar Jirakran2Pimpayao Sodsai3Siriwan Klinchanhom4Monojit Debnath5Agnieska Basta-Kaim6Marta Kubera7Abbas F. Almulla8Atapol Sughondhabirom9Department of Psychiatry, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University and The Thai Red Cross Society, Bangkok 10330, ThailandDepartment of Psychiatry, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University and The Thai Red Cross Society, Bangkok 10330, ThailandDepartment of Psychiatry, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University and The Thai Red Cross Society, Bangkok 10330, ThailandCenter of Excellence in Immunology and Immune-Mediated Diseases, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandCenter of Excellence in Immunology and Immune-Mediated Diseases, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore 560 029, IndiaDepartment of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, PolandDepartment of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, PolandDepartment of Psychiatry, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University and The Thai Red Cross Society, Bangkok 10330, ThailandDepartment of Psychiatry, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University and The Thai Red Cross Society, Bangkok 10330, ThailandAdverse 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.https://www.mdpi.com/2073-4409/11/9/1564early lifetime traumadepressionmood disordersinflammationneuroimmunecytokines |
| spellingShingle | Michael Maes Muanpetch Rachayon Ketsupar Jirakran Pimpayao Sodsai Siriwan Klinchanhom Monojit Debnath Agnieska Basta-Kaim Marta Kubera Abbas F. Almulla Atapol Sughondhabirom Adverse Childhood Experiences Predict the Phenome of Affective Disorders and These Effects Are Mediated by Staging, Neuroimmunotoxic and Growth Factor Profiles Cells early lifetime trauma depression mood disorders inflammation neuroimmune cytokines |
| title | Adverse Childhood Experiences Predict the Phenome of Affective Disorders and These Effects Are Mediated by Staging, Neuroimmunotoxic and Growth Factor Profiles |
| title_full | Adverse Childhood Experiences Predict the Phenome of Affective Disorders and These Effects Are Mediated by Staging, Neuroimmunotoxic and Growth Factor Profiles |
| title_fullStr | Adverse Childhood Experiences Predict the Phenome of Affective Disorders and These Effects Are Mediated by Staging, Neuroimmunotoxic and Growth Factor Profiles |
| title_full_unstemmed | Adverse Childhood Experiences Predict the Phenome of Affective Disorders and These Effects Are Mediated by Staging, Neuroimmunotoxic and Growth Factor Profiles |
| title_short | Adverse Childhood Experiences Predict the Phenome of Affective Disorders and These Effects Are Mediated by Staging, Neuroimmunotoxic and Growth Factor Profiles |
| title_sort | adverse childhood experiences predict the phenome of affective disorders and these effects are mediated by staging neuroimmunotoxic and growth factor profiles |
| topic | early lifetime trauma depression mood disorders inflammation neuroimmune cytokines |
| url | https://www.mdpi.com/2073-4409/11/9/1564 |
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