[en] The experience of adversity in childhood has been associated with poor health outcomes in adulthood. In search of the biological mechanisms underlying these effects, research so far focused on alterations of DNA methylation or shifts in transcriptomic profiles. The level of protein, however, has been largely neglected. We utilized mass spectrometry to investigate the proteome of CD14(+) monocytes in healthy adults reporting childhood adversity and a control group before and after psychosocial stress exposure. Particular proteins involved in (i) immune processes, such as neutrophil-related proteins, (ii) protein metabolism, or (iii) proteins related to mitochondrial biology, such as those involved in energy production processes, were upregulated in participants reporting exposure to adversity in childhood. This functional triad was further corroborated by protein interaction- and co-expression analyses, was independent of stress exposure, i.e. observed at both pre- and post-stress time points, and became evident especially in females. In line with the mitochondrial allostatic load model, our findings provide evidence for the long-term effects of childhood adversity on mitochondrial biology.
Disciplines :
Neurosciences & behavior
Author, co-author :
Zang, Johannes C. S.
May, Caroline
Hellwig, Birte
Moser, Dirk
Hengstler, Jan G.
Cole, Steve
Heinrichs, Markus
Rahnenführer, Jörg
Marcus, Katrin
Kumsta, Robert ; University of Luxembourg > Faculty of Humanities, Education and Social Sciences (FHSE) > Department of Behavioural and Cognitive Sciences (DBCS)
External co-authors :
yes
Language :
English
Title :
Proteome analysis of monocytes implicates altered mitochondrial biology in adults reporting adverse childhood experiences.
Publication date :
2023
Journal title :
Translational Psychiatry
ISSN :
2158-3188
Publisher :
Springer Nature, New-York, United States - New York
Kessler RC, McLaughlin KA, Green JG, Gruber MJ, Sampson NA, Zaslavsky AM, et al. Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys. Br J Psychiatry. 2010;197:378–85.
Kessler RC, Üstün TB. The WHO World Mental Health Surveys: global perspectives on the epidemiology of mental disorders. Cambridge, New York, Geneva: Cambridge University Press; Published in collaboration with the World Health Organization; 2008.
Gilbert R, Widom CS, Browne K, Fergusson D, Webb E, Janson S. Burden and consequences of child maltreatment in high-income countries. Lancet. 2009;373:68–81.
Repetti RL, Taylor SE, Seeman TE. Risky families: family social environments and the mental and physical health of offspring. Psychol Bull. 2002;128:330–66.
Heim C, Newport DJ, Bonsall R, Miller AH, Nemeroff CB. Altered pituitary-adrenal axis responses to provocative challenge tests in adult survivors of childhood abuse. Am J Psychiatry. 2001;158:575–81.
Heim C, Newport DJ, Heit S, Graham YP, Wilcox M, Bonsall R, et al. Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. JAMA 2000;284:592–7.
Danese A, Lewis SJ. Psychoneuroimmunology of early-life stress: the hidden wounds of childhood trauma? Neuropsychopharmacology 2017;42:99–114.
Trickett PK, Gordis E, Peckins MK, Susman EJ. Stress reactivity in maltreated and comparison male and female young adolescents. Child Maltreat. 2014;19:27–37.
Voellmin A, Winzeler K, Hug E, Wilhelm FH, Schaefer V, Gaab J, et al. Blunted endocrine and cardiovascular reactivity in young healthy women reporting a history of childhood adversity. Psychoneuroendocrinology 2015;51:58–67.
Danese A, Baldwin JR. Hidden wounds? Inflammatory links between childhood trauma and psychopathology. Annu Rev Psychol. 2017;68:517–44.
Baumeister D, Akhtar R, Ciufolini S, Pariante CM, Mondelli V. Childhood trauma and adulthood inflammation: a meta-analysis of peripheral C-reactive protein, interleukin-6 and tumour necrosis factor-α. Mol Psychiatry. 2016;21:642–9.
Picard M, McEwen BS. Psychological stress and mitochondria: a systematic review. Psychosom Med. 2018;80:141–53.
Monlun M, Hyernard C, Blanco P, Lartigue L, Faustin B. Mitochondria as molecular platforms integrating multiple innate immune signalings. J Mol Biol. 2017;429:1–13.
Picard M, Juster R-P, McEwen BS. Mitochondrial allostatic load puts the ‘gluc’ back in glucocorticoids. Nat Rev Endocrinol. 2014;10:303–10.
Picard M, McEwen BS, Epel ES, Sandi C. An energetic view of stress: focus on mitochondria. Front Neuroendocrinol. 2018;49:72–85.
Picard M, Prather AA, Puterman E, Cuillerier A, Coccia M, Aschbacher K, et al. A mitochondrial health index sensitive to mood and caregiving stress. Biol Psychiatry. 2018;84:9–17.
Turecki G, Meaney MJ. Effects of the social environment and stress on glucocorticoid receptor gene methylation: a systematic review. Biol Psychiatry. 2016;79:87–96.
Castro-Catala M, de, van Nierop M, Barrantes-Vidal N, Cristóbal-Narváez P, Sheinbaum T, Kwapil TR, et al. Childhood trauma, BDNF Val66Met and subclinical psychotic experiences. Attempt at replication in two independent samples. J Psychiatr Res. 2016;83:121–9.
Halldorsdottir T, Matos APS, de, Awaloff Y, Arnarson EÖ, Craighead WE, Binder EB. FKBP5 moderation of the relationship between childhood trauma and maladaptive emotion regulation strategies in adolescents. Psychoneuroendocrinology 2017;84:61–5.
Ramo-Fernández L, Gumpp AM, Boeck C, Krause S, Bach AM, Waller C, et al. Associations between childhood maltreatment and DNA methylation of the oxytocin receptor gene in immune cells of mother-newborn dyads. Transl Psychiatry. 2021;11:449.
Ramo-Fernández L, Karabatsiakis A, Boeck C, Bach AM, Gumpp AM, Mavioglu RN, et al. Characterization of the effects of age and childhood maltreatment on ELOVL2 DNA methylation. Dev Psychopathol. 2022;34:864–74.
Bick J, Naumova O, Hunter S, Barbot B, Lee M, Luthar SS, et al. Childhood adversity and DNA methylation of genes involved in the hypothalamus-pituitary-adrenal axis and immune system: whole-genome and candidate-gene associations. Dev Psychopathol. 2012;24:1417–25.
Houtepen LC, Vinkers CH, Carrillo-Roa T, Hiemstra M, van Lier PA, Meeus W, et al. Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans. Nat Commun. 2016;7:10967.
Mehta D, Klengel T, Conneely KN, Smith AK, Altmann A, Pace TW, et al. Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder. Proc Natl Acad Sci USA. 2013;110:8302–7.
Breen MS, Tylee DS, Maihofer AX, Neylan TC, Mehta D, Binder EB, et al. PTSD blood transcriptome mega-analysis: Shared inflammatory pathways across biological sex and modes of trauma. Neuropsychopharmacology 2018;43:469–81.
Cole SW, Hawkley LC, Arevalo JM, Sung CY, Rose RM, Cacioppo JT. Social regulation of gene expression in human leukocytes. Genome Biol. 2007;8:R189.
Cole SW, Hawkley LC, Arevalo JMG, Cacioppo JT. Transcript origin analysis identifies antigen-presenting cells as primary targets of socially regulated gene expression in leukocytes. Proc Natl Acad Sci USA. 2011;108:3080–5.
O’Donovan A, Sun B, Cole SW, Rempel H, Lenoci M, Pulliam L, et al. Transcriptional control of monocyte gene expression in post-traumatic stress disorder. Dis Markers. 2011;30:123–32.
Miller GE, Murphy MLM, Cashman R, Ma R, Ma J, Arevalo JMG, et al. Greater inflammatory activity and blunted glucocorticoid signaling in monocytes of chronically stressed caregivers. Brain Behav Immun. 2014;41:191–9.
Miller GE, Chen E, Sze J, Marin T, Arevalo JMG, Doll R, et al. A functional genomic fingerprint of chronic stress in humans: Blunted glucocorticoid and increased NF-κB signaling. Biol Psychiatry. 2008;64:266–72.
Schwaiger M, Grinberg M, Moser D, Zang JCS, Heinrichs M, Hengstler JG, et al. Altered stress-induced regulation of genes in monocytes in adults with a history of childhood adversity. Neuropsychopharmacology 2016;41:2530–40.
Liu Y, Beyer A, Aebersold R. On the dependency of cellular protein levels on mRNA abundance. Cell 2016;165:535–50.
Schwanhäusser B, Busse D, Li N, Dittmar G, Schuchhardt J, Wolf J, et al. Global quantification of mammalian gene expression control. Nature 2011;473:337–42.
Vogel C, Marcotte EM. Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nat Rev Genet. 2012;13:227–32.
Kirschbaum C, Pirke KM, Hellhammer DH. The ‘Trier Social Stress Test’–a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 1993;28:76–81.
R Core Team. R: A language and environment for statistical computing. https://www.R-project.org/; 2017.
Ritchie ME, Phipson B, Di WU, Hu Y, Law CW, Shi W, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43:e47.
Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008;9:559.
Kuleshov MV, Jones MR, Rouillard AD, Fernandez NF, Duan Q, Wang Z, et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 2016;44:W90–7.
Alexa A, Rahnenfuhrer J. topGO: enrichment analysis for gene ontology. R package version 2.38.1.; 2019.
Yu G, Li F, Qin Y, Bo X, Wu Y, Wang S. GOSemSim: an R package for measuring semantic similarity among GO terms and gene products. Bioinformatics 2010;26:976–8.
Rath S, Sharma R, Gupta R, Ast T, Chan C, Durham TJ, et al. MitoCarta3.0: an updated mitochondrial proteome now with sub-organelle localization and pathway annotations: An updated mitochondrial proteome now with sub-organelle localization and pathway annotations. Nucleic Acids Res. 2021;49:D1541–D1547.
Langfelder P, Luo R, Oldham MC, Horvath S. Is my network module preserved and reproducible? PLoS Comput Biol. 2011;7:e1001057.
Hoffman GE, Schadt EE. variancePartition: interpreting drivers of variation in complex gene expression studies. BMC Bioinformatics. 2016;17:483.
Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A, et al. STRING v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res. 2012;41:D808–15.
Lou Y, Han M, Liu H, Niu Y, Liang Y, Guo J, et al. Essential roles of S100A10 in toll-like receptor signaling and immunity to infection. Cell Mol Immunol. 2019; 17:1053–1062.
Andrés Cerezo L, Šumová B, Prajzlerová K, Veigl D, Damgaard D, Nielsen CH, et al. Calgizzarin (S100A11): a novel inflammatory mediator associated with disease activity of rheumatoid arthritis. Arthritis Res Ther. 2017;19:79.
Tyrka AR, Parade SH, Price LH, Kao H-T, Porton B, Philip NS, et al. Alterations of mitochondrial DNA copy number and telomere length with early adversity and psychopathology. Biol Psychiatry. 2016;79:78–86.
Boeck C, Koenig AM, Schury K, Geiger ML, Karabatsiakis A, Wilker S, et al. Inflammation in adult women with a history of child maltreatment: The involvement of mitochondrial alterations and oxidative stress. Mitochondrion 2016;30:197–207.
Wohleb ES, McKim DB, Sheridan JF, Godbout JP. Monocyte trafficking to the brain with stress and inflammation: a novel axis of immune-to-brain communication that influences mood and behavior. Front Neurosci. 2014;8:447.
Wohleb ES, Delpech J-C. Dynamic cross-talk between microglia and peripheral monocytes underlies stress-induced neuroinflammation and behavioral consequences. Prog Neuropsychopharmacol Biol Psychiatry. 2017;79:40–8.
Gumpp AM, Boeck C, Behnke A, Bach AM, Ramo-Fernández L, Welz T, et al. Childhood maltreatment is associated with changes in mitochondrial bioenergetics in maternal, but not in neonatal immune cells. Proc Natl Acad Sci USA. 2020;117:24778–84.
Gyllenhammer LE, Picard M, McGill MA, Boyle KE, Vawter MP, Rasmussen JM, et al. Prospective association between maternal allostatic load during pregnancy and child mitochondrial content and bioenergetic capacity. Psychoneuroendocrinology 2022;144:105868.
