PMID- 35870669 OWN - NLM STAT- MEDLINE DCOM- 20221013 LR - 20230314 IS - 1090-2139 (Electronic) IS - 0889-1591 (Linking) VI - 106 DP - 2022 Nov TI - Childhood trauma and LPS-stimulated inflammation in adulthood: Results from the Netherlands Study of Depression and Anxiety. PG - 21-29 LID - S0889-1591(22)00332-4 [pii] LID - 10.1016/j.bbi.2022.07.158 [doi] AB - BACKGROUND: Childhood trauma (CT) is robustly associated with psychiatric disorders including major depressive and anxiety disorders across the life span. The innate immune system may play a role in the relation between CT and stress-related psychopathology. However, whether CT influences the innate production capacity of cytokine levels following ex vivo stimulation by lipopolysaccharide (LPS), is currently unknown. METHODS: Using data from the Netherlands Study of Depression and Anxiety (NESDA, n=1237), we examined whether CT (emotional neglect, emotional, physical, and sexual abuse before the age of 16), assessed by the Childhood Trauma Interview, was associated with levels in supernatants of interferon (IFN)gamma, interleukin-2 (IL-2), IL-4, IL-6, IL-8, IL-10, IL-18, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, matrix metalloproteinase-2 (MMP-2), TNFalpha and TNFbeta after ex vivo stimulation with LPS. Cytokines were analysed individually and cumulatively (overall inflammation index and number of cytokines in high-risk quartile (HRQ)) using linear regression analyses. RESULTS: After adjustment for demographic, lifestyle, and health-related covariates, total CT severity was associated with the overall inflammation index (beta = 0.085, P(FDR) = 0.011), the number of cytokines in HRQ (beta = 0.063, P(FDR) = 0.036), and individual markers of IL-2 (beta = 0.067, P(FDR) = 0.036), IL-6 (beta = 0.091 P(FDR) = 0.011), IL-8 (beta = 0.085 P(FDR) = 0.011), IL-10 (beta = 0.094 P(FDR) = 0.011), MCP-1 (beta = 0.081 P(FDR) = 0.011), MIP-1alpha (beta = 0.061 P(FDR) = 0.047), MIP1-beta (beta = 0.077 P(FDR) = 0.016), MMP-2 (beta = 0.070 P(FDR) = 0.027), and TNFbeta (beta = 0.078 P(FDR) = 0.016). Associations were strongest for individuals with severe CT, reporting multiple types or higher frequencies of trauma. Half of the findings persisted after adjustment for psychiatric status. The findings were consistent across different CT types. CONCLUSION: Childhood Trauma is associated with increased LPS-stimulated cytokine levels, with evidence for a dose-response relationship. Our results highlight a dysregulated innate immune system capacity in adults with CT, which could contribute to an increased vulnerability for psychopathology and somatic disorders across the lifespan. CI - Copyright (c) 2022 The Authors. Published by Elsevier Inc. All rights reserved. FAU - de Koning, Ricki M AU - de Koning RM AD - Amsterdam UMC location Vrije University Amsterdam, Department of Psychiatry, Boelelaan 1117, Amsterdam, The Netherlands, Amsterdam Public Health (Mental Health program) and Amsterdam Neuroscience (Mood, Anxiety, Psychosis, Stress & Sleep program) research institutes, Amsterdam, the Netherlands. Electronic address: rickidekoning@gmail.com. FAU - Kuzminskaite, Erika AU - Kuzminskaite E AD - Amsterdam UMC location Vrije University Amsterdam, Department of Psychiatry, Boelelaan 1117, Amsterdam, The Netherlands, Amsterdam Public Health (Mental Health program) and Amsterdam Neuroscience (Mood, Anxiety, Psychosis, Stress & Sleep program) research institutes, Amsterdam, the Netherlands. Electronic address: e.kuzminskaite@amsterdamumc.nl. FAU - Vinkers, Christiaan H AU - Vinkers CH AD - Amsterdam UMC location Vrije University Amsterdam, Department of Psychiatry, Boelelaan 1117, Amsterdam, The Netherlands, Amsterdam Public Health (Mental Health program) and Amsterdam Neuroscience (Mood, Anxiety, Psychosis, Stress & Sleep program) research institutes, Amsterdam, the Netherlands; GGZ inGeest Mental Health Care, Amsterdam, The Netherlands. Electronic address: c.vinkers@amsterdamumc.nl. FAU - Giltay, Erik J AU - Giltay EJ AD - Leiden University Medical Center, Department of Psychiatry, Leiden, The Netherlands. Electronic address: e.j.giltay@lumc.nl. FAU - Penninx, Brenda W J H AU - Penninx BWJH AD - Amsterdam UMC location Vrije University Amsterdam, Department of Psychiatry, Boelelaan 1117, Amsterdam, The Netherlands, Amsterdam Public Health (Mental Health program) and Amsterdam Neuroscience (Mood, Anxiety, Psychosis, Stress & Sleep program) research institutes, Amsterdam, the Netherlands. Electronic address: b.penninx@amsterdamumc.nl. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220720 PL - Netherlands TA - Brain Behav Immun JT - Brain, behavior, and immunity JID - 8800478 RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL3) RN - 0 (Chemokine CCL4) RN - 0 (Cytokines) RN - 0 (Interleukin-18) RN - 0 (Interleukin-2) RN - 0 (Interleukin-6) RN - 0 (Interleukin-8) RN - 0 (Lipopolysaccharides) RN - 0 (Tumor Necrosis Factor-alpha) RN - 130068-27-8 (Interleukin-10) RN - 207137-56-2 (Interleukin-4) RN - 9008-11-1 (Interferons) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) SB - IM MH - Adult MH - *Adverse Childhood Experiences MH - *Anxiety/immunology MH - Anxiety Disorders/immunology MH - Chemokine CCL2 MH - Chemokine CCL3 MH - Chemokine CCL4 MH - Cytokines/metabolism MH - *Depression/immunology MH - Depressive Disorder, Major/immunology MH - Humans MH - *Immunity, Innate MH - Inflammation MH - Interferons MH - Interleukin-10 MH - Interleukin-18 MH - Interleukin-2 MH - Interleukin-4 MH - Interleukin-6 MH - Interleukin-8 MH - Lipopolysaccharides MH - Matrix Metalloproteinase 2 MH - Netherlands/epidemiology MH - Tumor Necrosis Factor-alpha OTO - NOTNLM OT - Childhood Trauma OT - Cytokines OT - Immune system OT - Inflammation OT - LPS COIS- Declaration of Competing Interest BP has received unrestricted research funding from Boehringer Ingelheim and Jansen Research b.v. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/07/24 06:00 MHDA- 2022/10/14 06:00 CRDT- 2022/07/23 19:26 PHST- 2022/04/09 00:00 [received] PHST- 2022/06/30 00:00 [revised] PHST- 2022/07/18 00:00 [accepted] PHST- 2022/07/24 06:00 [pubmed] PHST- 2022/10/14 06:00 [medline] PHST- 2022/07/23 19:26 [entrez] AID - S0889-1591(22)00332-4 [pii] AID - 10.1016/j.bbi.2022.07.158 [doi] PST - ppublish SO - Brain Behav Immun. 2022 Nov;106:21-29. doi: 10.1016/j.bbi.2022.07.158. Epub 2022 Jul 20.