{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T05:58:18Z","timestamp":1781675898311,"version":"3.54.5"},"reference-count":100,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T00:00:00Z","timestamp":1631750400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T00:00:00Z","timestamp":1631750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100010583","name":"Universit\u00e4t Konstanz","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010583","id-type":"DOI","asserted-by":"publisher"}]},{"name":"vivo international e.V."},{"DOI":"10.13039\/501100010583","name":"Universit\u00e4t Konstanz","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100010583","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The aftermath of traumatization lives on in the neural and epigenetic traces creating a momentum of affliction in the psychological and social realm. Can psychotherapy reorganise these memories through changes in DNA methylation signatures? Using a randomised controlled parallel group design, we examined methylome-wide changes in saliva samples of 84 female former child soldiers from Eastern DR Congo before and six months after Narrative Exposure Therapy. Treatment predicted differentially methylated positions (DMPs) related to<jats:italic>ALCAM<\/jats:italic>,<jats:italic>RIPOR2<\/jats:italic>,<jats:italic>AFAP1<\/jats:italic>and<jats:italic>MOCOS<\/jats:italic>. In addition, treatment associations overlapped at gene level with baseline clinical and social outcomes. Treatment related DMPs are involved in memory formation\u2014the key agent in trauma focused treatments\u2014and enriched for molecular pathways commonly affected by trauma related disorders. Results were partially replicated in an independent sample of 53 female former child soldiers from Northern Uganda. Our results suggest a molecular impact of psychological treatment in women with war-related childhood trauma.<\/jats:p><jats:p><jats:bold>Trial registration<\/jats:bold>: Addressing Heightened Levels of Aggression in Traumatized Offenders With Psychotherapeutic Means (ClinicalTrials.gov Identifier: NCT02992561, 14\/12\/2016).<\/jats:p>","DOI":"10.1038\/s41598-021-98067-9","type":"journal-article","created":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T10:02:41Z","timestamp":1631786561000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["DNA methylation changes following narrative exposure therapy in a randomized controlled trial with female former child soldiers"],"prefix":"10.1038","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct02992561","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Samuel","family":"Carleial","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"N\u00e4tt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Untern\u00e4hrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Elbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katy","family":"Robjant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Wilker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanja","family":"Vukojevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris-Tatjana","family":"Kolassa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja C.","family":"Zeller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Koebach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,16]]},"reference":[{"key":"98067_CR1","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1007\/978-1-4419-5722-1_14","volume-title":"Trauma Rehabilitation After War and Conflict: Community and Individual Perspectives","author":"E Schauer","year":"2010","unstructured":"Schauer, E. & Elbert, T. In Trauma Rehabilitation After War and Conflict: Community and Individual Perspectives (ed. Erin, M.) 311\u2013360 (Springer, 2010)."},{"key":"98067_CR2","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1111\/j.1469-7610.2012.02620.x","volume":"54","author":"TS Betancourt","year":"2013","unstructured":"Betancourt, T. S. et al. Research review: Psychosocial adjustment and mental health in former child soldiers\u2014a systematic review of the literature and recommendations for future research. J. Child Psychol. Psychiatry 54, 17\u201336 (2013).","journal-title":"J. Child Psychol. Psychiatry"},{"key":"98067_CR3","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1027\/0044-3409\/a000018","volume":"218","author":"M Schauer","year":"2010","unstructured":"Schauer, M. & Elbert, T. Dissociation following traumatic stress\u2014etiology and treatment. Zeitschrift f\u00fcr Psychologie \/ J. Psychol. 218, 109\u2013127. https:\/\/doi.org\/10.1027\/0044-3409\/a000018 (2010).","journal-title":"Zeitschrift f\u00fcr Psychologie \/ J. Psychol."},{"key":"98067_CR4","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1007\/s00406-010-0144-8","volume":"260","author":"T Elbert","year":"2010","unstructured":"Elbert, T., Weierstall, R. & Schauer, M. Fascination violence: On mind and brain of man hunters. Eur. Arch. Psychiatry Clin. Neurosci. 260, 100\u2013105 (2010).","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"98067_CR5","volume-title":"The End of Stress as We Know It","author":"BS McEwen","year":"2002","unstructured":"McEwen, B. S. & Lasley, E. N. The End of Stress as We Know It (Joseph Henry Press, 2002)."},{"key":"98067_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/nrdp.2015.57","volume":"1","author":"R Yehuda","year":"2015","unstructured":"Yehuda, R. et al. Post-traumatic stress disorder. Nat. Rev. Dis. Primers. 1, 1\u201322 (2015).","journal-title":"Nat. Rev. Dis. Primers."},{"key":"98067_CR7","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/1471-244X-13-40","volume":"13","author":"H Gola","year":"2013","unstructured":"Gola, H. et al. Posttraumatic stress disorder is associated with an enhanced spontaneous production of pro-inflammatory cytokines by peripheral blood mononuclear cells. BMC Psychiatry 13, 40 (2013).","journal-title":"BMC Psychiatry"},{"key":"98067_CR8","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.mhp.2018.04.002","volume":"13","author":"ML Geiger","year":"2019","unstructured":"Geiger, M. L. et al. Investigating the effects of childhood maltreatment on pro-inflammatory signaling: The influence of cortisol and DHEA on cytokine secretion ex vivo. Mental Health Prevent. 13, 176\u2013186 (2019).","journal-title":"Mental Health Prevent."},{"key":"98067_CR9","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.mito.2016.08.006","volume":"30","author":"C Boeck","year":"2016","unstructured":"Boeck, C. et al. Inflammation in adult women with a history of child maltreatment: The involvement of mitochondrial alterations and oxidative stress. Mitochondrion 30, 197\u2013207 (2016).","journal-title":"Mitochondrion"},{"key":"98067_CR10","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s40303-015-0007-3","volume":"3","author":"A Karabatsiakis","year":"2015","unstructured":"Karabatsiakis, A. et al. Metabolite profiling in posttraumatic stress disorder. J. Mol. Psychiatry 3, 2 (2015).","journal-title":"J. Mol. Psychiatry"},{"key":"98067_CR11","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1016\/j.biopsych.2018.02.007","volume":"83","author":"SH Mellon","year":"2018","unstructured":"Mellon, S. H., Gautam, A., Hammamieh, R., Jett, M. & Wolkowitz, O. M. Metabolism, metabolomics, and inflammation in posttraumatic stress disorder. Biol. Psychiat. 83, 866\u2013875 (2018).","journal-title":"Biol. Psychiat."},{"key":"98067_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-018-21763-6","volume":"8","author":"AM Koenig","year":"2018","unstructured":"Koenig, A. M. et al. Serum profile changes in postpartum women with a history of childhood maltreatment: A combined metabolite and lipid fingerprinting study. Sci. Rep. 8, 1\u201310 (2018).","journal-title":"Sci. Rep."},{"key":"98067_CR13","doi-asserted-by":"publisher","first-page":"1553","DOI":"10.2217\/epi-2016-0083","volume":"8","author":"J Ryan","year":"2016","unstructured":"Ryan, J., Chaudieu, I., Ancelin, M.-L. & Saffery, R. Biological underpinnings of trauma and post-traumatic stress disorder: Focusing on genetics and epigenetics. Epigenomics 8, 1553\u20131569 (2016).","journal-title":"Epigenomics"},{"key":"98067_CR14","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1016\/j.neuron.2015.05.036","volume":"86","author":"T Klengel","year":"2015","unstructured":"Klengel, T. & Binder, E. B. Epigenetics of stress-related psychiatric disorders and gene \u00d7 environment interactions. Neuron 86, 1343\u20131357 (2015).","journal-title":"Neuron"},{"key":"98067_CR15","doi-asserted-by":"publisher","first-page":"593","DOI":"10.2217\/epi.15.11","volume":"7","author":"CH Vinkers","year":"2015","unstructured":"Vinkers, C. H. et al. Traumatic stress and human DNA methylation: A critical review. Epigenomics 7, 593\u2013608 (2015).","journal-title":"Epigenomics"},{"key":"98067_CR16","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1146\/annurev-clinpsy-050718-095530","volume":"16","author":"KJ O'Donnell","year":"2020","unstructured":"O\u2019Donnell, K. J. & Meaney, M. J. Epigenetics, development, and psychopathology. Annu. Rev. Clin. Psychol. 16, 327\u2013350 (2020).","journal-title":"Annu. Rev. Clin. Psychol."},{"key":"98067_CR17","doi-asserted-by":"publisher","first-page":"140","DOI":"10.3390\/genes10020140","volume":"10","author":"CJ Blacker","year":"2019","unstructured":"Blacker, C. J., Frye, M. A., Morava, E., Kozicz, T. & Veldic, M. A review of epigenetics of PTSD in comorbid psychiatric conditions. Genes 10, 140 (2019).","journal-title":"Genes"},{"key":"98067_CR18","doi-asserted-by":"publisher","first-page":"10274","DOI":"10.1523\/JNEUROSCI.1526-14.2014","volume":"34","author":"V Vukojevic","year":"2014","unstructured":"Vukojevic, V. et al. Epigenetic modification of the glucocorticoid receptor gene is linked to traumatic memory and post-traumatic stress disorder risk in genocide survivors. J. Neurosci. 34, 10274\u201310284 (2014).","journal-title":"J. Neurosci."},{"key":"98067_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-018-36689-2","volume":"9","author":"L Ramo-Fern\u00e1ndez","year":"2019","unstructured":"Ramo-Fern\u00e1ndez, L. et al. The effects of childhood maltreatment on epigenetic regulation of stress-response associated genes: An intergenerational approach. Sci. Rep. 9, 1\u201312 (2019).","journal-title":"Sci. Rep."},{"key":"98067_CR20","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2017.153","volume":"7","author":"F Serpeloni","year":"2017","unstructured":"Serpeloni, F. et al. Grandmaternal stress during pregnancy and DNA methylation of the third generation: An epigenome-wide association study. Transl. Psychiatry 7, e1202. https:\/\/doi.org\/10.1038\/tp.2017.153 (2017).","journal-title":"Transl. Psychiatry"},{"key":"98067_CR21","doi-asserted-by":"publisher","first-page":"269","DOI":"10.3389\/fgene.2019.00269","volume":"10","author":"F Serpeloni","year":"2019","unstructured":"Serpeloni, F. et al. Does prenatal stress shape postnatal resilience? An epigenome-wide study on violence and mental health in humans. Front. Genet. 10, 269. https:\/\/doi.org\/10.3389\/fgene.2019.00269 (2019).","journal-title":"Front. Genet."},{"key":"98067_CR22","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1080\/15592294.2015.1039221","volume":"10","author":"E Braithwaite","year":"2015","unstructured":"Braithwaite, E., Kundakovic, M., Ramchandani, P., Murphy, S. & Champagne, F. Maternal prenatal depressive symptoms predict infant NR3C1 1F and BDNF IV DNA methylation. Epigenetics 10, 408\u2013417 (2015).","journal-title":"Epigenetics"},{"key":"98067_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-018-05445-5","volume":"9","author":"B Horsthemke","year":"2018","unstructured":"Horsthemke, B. A critical view on transgenerational epigenetic inheritance in humans. Nat. Commun. 9, 1\u20134 (2018).","journal-title":"Nat. Commun."},{"key":"98067_CR24","doi-asserted-by":"publisher","first-page":"e86822","DOI":"10.1371\/journal.pone.0086822","volume":"9","author":"C Guillemin","year":"2014","unstructured":"Guillemin, C. et al. DNA methylation signature of childhood chronic physical aggression in T cells of both men and women. PLoS ONE 9, e86822 (2014).","journal-title":"PLoS ONE"},{"key":"98067_CR25","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1007\/s00702-018-1929-6","volume":"125","author":"C Ziegler","year":"2018","unstructured":"Ziegler, C. & Domschke, K. Epigenetic signature of MAOA and MAOB genes in mental disorders. J. Neural Transm. 125, 1581\u20131588 (2018).","journal-title":"J. Neural Transm."},{"key":"98067_CR26","first-page":"118","volume":"4","author":"R Yehuda","year":"2013","unstructured":"Yehuda, R. et al. Epigenetic biomarkers as predictors and correlates of symptom improvement following psychotherapy in combat veterans with PTSD. Front. Psych. 4, 118 (2013).","journal-title":"Front. Psych."},{"key":"98067_CR27","first-page":"1","volume":"2","author":"CH Vinkers","year":"2019","unstructured":"Vinkers, C. H. et al. Successful treatment of post-traumatic stress disorder reverses DNA methylation marks. Mol. Psychiatry 2, 1\u20138 (2019).","journal-title":"Mol. Psychiatry"},{"key":"98067_CR28","first-page":"113608","volume":"2","author":"KR Xulu","year":"2020","unstructured":"Xulu, K. R. et al. DNA methylation and psychotherapy response in trauma-exposed men with appetitive aggression. Psychiatry Res. 2, 113608 (2020).","journal-title":"Psychiatry Res."},{"key":"98067_CR29","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.biopsych.2012.01.034","volume":"72","author":"B Labonte","year":"2012","unstructured":"Labonte, B. et al. Differential glucocorticoid receptor exon 1B, 1C, and 1H expression and methylation in suicide completers with a history of childhood abuse. Biol. Psychiat. 72, 41\u201348 (2012).","journal-title":"Biol. Psychiat."},{"key":"98067_CR30","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.pharep.2018.10.004","volume":"71","author":"P Jaworska-Andryszewska","year":"2019","unstructured":"Jaworska-Andryszewska, P. & Rybakowski, J. K. Childhood trauma in mood disorders: Neurobiological mechanisms and implications for treatment. Pharmacol. Rep. 71, 112\u2013120 (2019).","journal-title":"Pharmacol. Rep."},{"key":"98067_CR31","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1038\/nn.2270","volume":"12","author":"PO McGowan","year":"2009","unstructured":"McGowan, P. O. et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat. Neurosci. 12, 342\u2013348 (2009).","journal-title":"Nat. Neurosci."},{"key":"98067_CR32","doi-asserted-by":"publisher","first-page":"103482","DOI":"10.1016\/j.brat.2019.103482","volume":"123","author":"K Robjant","year":"2019","unstructured":"Robjant, K. et al. The treatment of posttraumatic stress symptoms and aggression in female former child soldiers using adapted Narrative Exposure therapy\u2014a RCT in Eastern Democratic Republic of Congo. Behav. Res. Therapy 123, 103482 (2019).","journal-title":"Behav. Res. Therapy"},{"key":"98067_CR33","volume-title":"Narrative Exposure Therapy: A Short-Term Treatment for Traumatic Stress Disorders","author":"M Schauer","year":"2011","unstructured":"Schauer, M., Neuner, F. & Elbert, T. Narrative Exposure Therapy: A Short-Term Treatment for Traumatic Stress Disorders (Hogrefe Publishing, 2011)."},{"key":"98067_CR34","doi-asserted-by":"publisher","first-page":"28186","DOI":"10.3402\/ejpt.v6.28186","volume":"6","author":"U Schnyder","year":"2015","unstructured":"Schnyder, U. et al. Psychotherapies for PTSD: What do they have in common?. Eur. J. Psychotraumatol. 6, 28186 (2015).","journal-title":"Eur. J. Psychotraumatol."},{"key":"98067_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1017\/S1352465819000365","volume":"48","author":"M Hinsberger","year":"2020","unstructured":"Hinsberger, M. et al. Long-term effects of psychotherapy in a context of continuous community and gang violence: changes in aggressive attitude in high-risk South African adolescents. Behav. Cogn. Psychother. 48, 1\u201313 (2020).","journal-title":"Behav. Cogn. Psychother."},{"key":"98067_CR36","first-page":"255","volume-title":"Interventionen bei Gewalt- und Sexualstraft\u00e4tern: Risko-Management, Methoden und Konzepte der forensischen Therapie","author":"T Elbert","year":"2012","unstructured":"Elbert, T., Hermenau, K., Hecker, T., Weierstall, R. & Schauer, M. In Interventionen bei Gewalt- und Sexualstraft\u00e4tern: Risko-Management, Methoden und Konzepte der forensischen Therapie (eds Endras, J. et al.) 255\u2013276 (Medizinisch Wissenschaftliche Verlagsgesellschaft, 2012)."},{"key":"98067_CR37","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/978-3-319-07109-1_12","volume-title":"Evidence Based Treatments for Trauma-Related Psychological Disorders","author":"T Elbert","year":"2015","unstructured":"Elbert, T., Schauer, M. & Neuner, F. Evidence Based Treatments for Trauma-Related Psychological Disorders 229\u2013253 (Springer, 2015)."},{"key":"98067_CR38","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.neuropharm.2006.07.027","volume":"52","author":"G Lynch","year":"2007","unstructured":"Lynch, G., Rex, C. S. & Gall, C. M. LTP consolidation: Substrates, explanatory power, and functional significance. Neuropharmacology 52, 12\u201323 (2007).","journal-title":"Neuropharmacology"},{"key":"98067_CR39","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.brainres.2014.12.007","volume":"1621","author":"JW Rudy","year":"2015","unstructured":"Rudy, J. W. Actin dynamics and the evolution of the memory trace. Brain Res. 1621, 17\u201328 (2015).","journal-title":"Brain Res."},{"key":"98067_CR40","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/s10059-012-0097-z","volume":"34","author":"H Mun","year":"2012","unstructured":"Mun, H. & Jeon, T. J. Regulation of actin cytoskeleton by Rap1 binding to RacGEF1. Mol. Cells 34, 71\u201376 (2012).","journal-title":"Mol. Cells"},{"key":"98067_CR41","doi-asserted-by":"publisher","first-page":"E1946","DOI":"10.1073\/pnas.1501989112","volume":"112","author":"CR Bye","year":"2015","unstructured":"Bye, C. R., J\u00f6nsson, M. E., Bj\u00f6rklund, A., Parish, C. L. & Thompson, L. H. Transcriptome analysis reveals transmembrane targets on transplantable midbrain dopamine progenitors. Proc. Natl. Acad. Sci. 112, E1946\u2013E1955 (2015).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"98067_CR42","doi-asserted-by":"publisher","first-page":"6656","DOI":"10.1523\/JNEUROSCI.0278-19.2019","volume":"39","author":"CR Bye","year":"2019","unstructured":"Bye, C. R., Rytova, V., Alsanie, W. F., Parish, C. L. & Thompson, L. H. Axonal growth of midbrain dopamine neurons is modulated by the cell adhesion molecule ALCAM through trans-heterophilic interactions with L1cam, Chl1, and semaphorins. J. Neurosci. 39, 6656\u20136667 (2019).","journal-title":"J. Neurosci."},{"key":"98067_CR43","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1521\/soco.2008.26.5.593","volume":"26","author":"ND Daw","year":"2008","unstructured":"Daw, N. D. & Shohamy, D. The cognitive neuroscience of motivation and learning. Soc. Cogn. 26, 593\u2013620 (2008).","journal-title":"Soc. Cogn."},{"key":"98067_CR44","doi-asserted-by":"publisher","first-page":"E1652","DOI":"10.1073\/pnas.1502295112","volume":"112","author":"J Menezes","year":"2015","unstructured":"Menezes, J. et al. Facilitation of fear extinction by novelty depends on dopamine acting on D1-subtype dopamine receptors in hippocampus. Proc. Natl. Acad. Sci. 112, E1652\u2013E1658 (2015).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"98067_CR45","doi-asserted-by":"publisher","first-page":"e54936","DOI":"10.7554\/eLife.54936","volume":"9","author":"LX Cai","year":"2020","unstructured":"Cai, L. X. et al. Distinct signals in medial and lateral VTA dopamine neurons modulate fear extinction at different times. Elife 9, e54936 (2020).","journal-title":"Elife"},{"key":"98067_CR46","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.nlm.2008.09.001","volume":"91","author":"L Mantzur","year":"2009","unstructured":"Mantzur, L., Joels, G. & Lamprecht, R. Actin polymerization in lateral amygdala is essential for fear memory formation. Neurobiol. Learn. Mem. 91, 85\u201388 (2009).","journal-title":"Neurobiol. Learn. Mem."},{"key":"98067_CR47","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1002\/hipo.20915","volume":"22","author":"H Motanis","year":"2012","unstructured":"Motanis, H. & Maroun, M. Differential involvement of protein synthesis and actin rearrangement in the reacquisition of contextual fear conditioning. Hippocampus 22, 494\u2013500 (2012).","journal-title":"Hippocampus"},{"key":"98067_CR48","doi-asserted-by":"publisher","first-page":"E524","DOI":"10.1073\/pnas.1614336114","volume":"114","author":"M-A L\u00e9cuyer","year":"2017","unstructured":"L\u00e9cuyer, M.-A. et al. Dual role of ALCAM in neuroinflammation and blood\u2013brain barrier homeostasis. Proc. Natl. Acad. Sci. 114, E524\u2013E533 (2017).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"98067_CR49","doi-asserted-by":"publisher","first-page":"3212","DOI":"10.1182\/blood-2005-09-3881","volume":"107","author":"AW Zimmerman","year":"2006","unstructured":"Zimmerman, A. W. et al. Long-term engagement of CD6 and ALCAM is essential for T-cell proliferation induced by dendritic cells. Blood 107, 3212\u20133220 (2006).","journal-title":"Blood"},{"key":"98067_CR50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jpsychires.2014.03.016","volume":"54","author":"J Morath","year":"2014","unstructured":"Morath, J. et al. The effect of trauma-focused therapy on the altered T cell distribution in individuals with PTSD: Evidence from a randomized controlled trial. J. Psychiatr. Res. 54, 1\u201310 (2014).","journal-title":"J. Psychiatr. Res."},{"key":"98067_CR51","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1016\/j.bbi.2009.07.003","volume":"23","author":"A Sommershof","year":"2009","unstructured":"Sommershof, A. et al. Substantial reduction of naive and regulatory T cells following traumatic stress. Brain Behav. Immun. 23, 1117\u20131124 (2009).","journal-title":"Brain Behav. Immun."},{"key":"98067_CR52","doi-asserted-by":"publisher","first-page":"3567","DOI":"10.1016\/j.febslet.2013.09.020","volume":"587","author":"A Roy","year":"2013","unstructured":"Roy, A. & Pahan, K. Ankyrin repeat and BTB\/POZ domain containing protein-2 inhibits the aggregation of alpha-synuclein: Implications for Parkinson\u2019s disease. FEBS Lett. 587, 3567\u20133574 (2013).","journal-title":"FEBS Lett."},{"key":"98067_CR53","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1091\/mbc.E17-08-0495","volume":"29","author":"KM Janisch","year":"2018","unstructured":"Janisch, K. M., McNeely, K. C., Dardick, J. M., Lim, S. H. & Dwyer, N. D. Kinesin-6 KIF20B is required for efficient cytokinetic furrowing and timely abscission in human cells. Mol. Biol. Cell 29, 166\u2013179 (2018).","journal-title":"Mol. Biol. Cell"},{"key":"98067_CR54","doi-asserted-by":"publisher","first-page":"4672","DOI":"10.1242\/dev.093286","volume":"140","author":"KM Janisch","year":"2013","unstructured":"Janisch, K. M. et al. The vertebrate-specific Kinesin-6, Kif20b, is required for normal cytokinesis of polarized cortical stem cells and cerebral cortex size. Development 140, 4672\u20134682 (2013).","journal-title":"Development"},{"key":"98067_CR55","doi-asserted-by":"publisher","first-page":"E1825","DOI":"10.1073\/pnas.1621433114","volume":"114","author":"HK Romero","year":"2017","unstructured":"Romero, H. K. et al. Inhibition of \u03b19\u03b110 nicotinic acetylcholine receptors prevents chemotherapy-induced neuropathic pain. Proc. Natl. Acad. Sci. 114, E1825\u2013E1832 (2017).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"98067_CR56","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.bone.2018.11.003","volume":"120","author":"L Baumann","year":"2019","unstructured":"Baumann, L. et al. Deletion of nicotinic acetylcholine receptor alpha9 in mice resulted in altered bone structure. Bone 120, 285\u2013296 (2019).","journal-title":"Bone"},{"key":"98067_CR57","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13148-019-0656-7","volume":"11","author":"PD Fransquet","year":"2019","unstructured":"Fransquet, P. D., Wrigglesworth, J., Woods, R. L., Ernst, M. E. & Ryan, J. The epigenetic clock as a predictor of disease and mortality risk: A systematic review and meta-analysis. Clin. Epigenetics 11, 1\u201317 (2019).","journal-title":"Clin. Epigenetics"},{"key":"98067_CR58","doi-asserted-by":"publisher","first-page":"101348","DOI":"10.1016\/j.arr.2021.101348","volume":"2","author":"L Oblak","year":"2021","unstructured":"Oblak, L., van der Zaag, J., Higgins-Chen, A. T., Levine, M. E. & Boks, M. P. A systematic review of biological, social and environmental factors associated with epigenetic clock acceleration. Ageing Res. Rev. 2, 101348 (2021).","journal-title":"Ageing Res. Rev."},{"key":"98067_CR59","first-page":"2","volume":"2","author":"NS Ferreira","year":"2020","unstructured":"Ferreira, N. S., Tostes, R. C., Paradis, P. & Schiffrin, E. L. Aldosterone, inflammation, immune system, and hypertension. Am. J. Hypertens. 2, 2 (2020).","journal-title":"Am. J. Hypertens."},{"key":"98067_CR60","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1016\/j.arcmed.2005.03.046","volume":"36","author":"E Emanuele","year":"2005","unstructured":"Emanuele, E., Geroldi, D., Minoretti, P., Coen, E. & Politi, P. Increased plasma aldosterone in patients with clinical depression. Arch. Med. Res. 36, 544\u2013548 (2005).","journal-title":"Arch. Med. Res."},{"key":"98067_CR61","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/1471-244X-3-15","volume":"3","author":"H Murck","year":"2003","unstructured":"Murck, H. et al. The renin-angiotensin-aldosterone system in patients with depression compared to controls\u2014a sleep endocrine study. BMC Psychiatry 3, 15 (2003).","journal-title":"BMC Psychiatry"},{"key":"98067_CR62","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.psyneuen.2019.05.026","volume":"107","author":"J Terock","year":"2019","unstructured":"Terock, J. et al. Differential activation of the renin-angiotensin-aldosterone-system in response to childhood and adulthood trauma. Psychoneuroendocrinology 107, 232\u2013240 (2019).","journal-title":"Psychoneuroendocrinology"},{"key":"98067_CR63","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.neulet.2016.11.064","volume":"649","author":"LA Averill","year":"2017","unstructured":"Averill, L. A. et al. Glutamate dysregulation and glutamatergic therapeutics for PTSD: Evidence from human studies. Neurosci. Lett. 649, 147\u2013155 (2017).","journal-title":"Neurosci. Lett."},{"key":"98067_CR64","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/j.yhbeh.2011.12.003","volume":"61","author":"PS Churchland","year":"2012","unstructured":"Churchland, P. S. & Winkielman, P. Modulating social behavior with oxytocin: How does it work? What does it mean?. Horm. Behav. 61, 392\u2013399 (2012).","journal-title":"Horm. Behav."},{"key":"98067_CR65","doi-asserted-by":"publisher","first-page":"25965","DOI":"10.1074\/jbc.M004515200","volume":"275","author":"NA Elshourbagy","year":"2000","unstructured":"Elshourbagy, N. A. et al. Receptor for the pain modulatory neuropeptides FF and AF is an orphan G protein-coupled receptor. J. Biol. Chem. 275, 25965\u201325971 (2000).","journal-title":"J. Biol. Chem."},{"key":"98067_CR66","doi-asserted-by":"publisher","first-page":"1810","DOI":"10.3390\/ijms18081810","volume":"18","author":"Y-T Lin","year":"2017","unstructured":"Lin, Y.-T. et al. NPFFR2 activates the HPA axis and induces anxiogenic effects in rodents. Int. J. Mol. Sci. 18, 1810. https:\/\/doi.org\/10.3390\/ijms18081810 (2017).","journal-title":"Int. J. Mol. Sci."},{"key":"98067_CR67","first-page":"337","volume":"6","author":"XR Zhu","year":"1999","unstructured":"Zhu, X. R., Netzer, R., B\u00f6hlke, K., Liu, Q. & Pongs, O. Structural and functional characterization of Kv6.2 a new gamma-subunit of voltage-gated potassium channel. Receptors Channels 6, 337\u2013350 (1999).","journal-title":"Receptors Channels"},{"key":"98067_CR68","doi-asserted-by":"publisher","first-page":"27291","DOI":"10.1074\/jbc.m910126199","volume":"275","author":"R Inatome","year":"2000","unstructured":"Inatome, R. et al. Identification of CRAM, a novel unc-33 gene family protein that associates with CRMP3 and protein-tyrosine kinase(s) in the developing rat brain. J. Biol. Chem. 275, 27291\u201327302. https:\/\/doi.org\/10.1074\/jbc.m910126199 (2000).","journal-title":"J. Biol. Chem."},{"key":"98067_CR69","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1747-1028-1-21","volume":"1","author":"TA Groothuis","year":"2006","unstructured":"Groothuis, T. A., Dantuma, N. P., Neefjes, J. & Salomons, F. A. Ubiquitin crosstalk connecting cellular processes. Cell Div. 1, 1\u20137 (2006).","journal-title":"Cell Div."},{"key":"98067_CR70","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0217885","volume":"14","author":"PRT Bowman","year":"2019","unstructured":"Bowman, P. R. T., Smith, G. L. & Gould, G. W. GLUT4 expression and glucose transport in human induced pluripotent stem cell-derived cardiomyocytes. PLoS ONE 14, e0217885. https:\/\/doi.org\/10.1371\/journal.pone.0217885 (2019).","journal-title":"PLoS ONE"},{"key":"98067_CR71","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1038\/nature02633","volume":"429","author":"M Kaneda","year":"2004","unstructured":"Kaneda, M. et al. Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature 429, 900\u2013903 (2004).","journal-title":"Nature"},{"key":"98067_CR72","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1016\/j.cell.2017.09.047","volume":"171","author":"H Stroud","year":"2017","unstructured":"Stroud, H. et al. Early-life gene expression in neurons modulates lasting epigenetic states. Cell 171, 1151\u20131164 (2017).","journal-title":"Cell"},{"key":"98067_CR73","doi-asserted-by":"publisher","first-page":"991","DOI":"10.3390\/genes6040991","volume":"6","author":"AM Andersen","year":"2015","unstructured":"Andersen, A. M., Dogan, M. V., Beach, S. R. & Philibert, R. A. Current and future prospects for epigenetic biomarkers of substance use disorders. Genes 6, 991\u20131022 (2015).","journal-title":"Genes"},{"key":"98067_CR74","first-page":"55","volume":"7","author":"R Philibert","year":"2016","unstructured":"Philibert, R. et al. Reversion of AHRR demethylation is a quantitative biomarker of smoking cessation. Front. Psych. 7, 55 (2016).","journal-title":"Front. Psych."},{"key":"98067_CR75","doi-asserted-by":"publisher","first-page":"821","DOI":"10.3390\/genes5030821","volume":"5","author":"T Mikeska","year":"2014","unstructured":"Mikeska, T. & Craig, J. M. DNA methylation biomarkers: Cancer and beyond. Genes 5, 821\u2013864 (2014).","journal-title":"Genes"},{"key":"98067_CR76","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/nrg2341","volume":"9","author":"MM Suzuki","year":"2008","unstructured":"Suzuki, M. M. & Bird, A. DNA methylation landscapes: Provocative insights from epigenomics. Nat. Rev. Genet. 9, 465\u2013476 (2008).","journal-title":"Nat. Rev. Genet."},{"key":"98067_CR77","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2020.533357","author":"K Robjant","year":"2020","unstructured":"Robjant, K. et al. Trauma, aggression, and post conflict perpetration of community violence in female former child soldiers\u2014A study in eastern DR congo. Front. Psychiatry https:\/\/doi.org\/10.3389\/fpsyt.2020.533357 (2020).","journal-title":"Front. Psychiatry"},{"key":"98067_CR78","unstructured":"Foa, E. & Capaldi, S. Manual for the administration and scoring of the PTSD symptom scale\u2013interview for DSM-5 (PSS-I-5). (2013)."},{"key":"98067_CR79","doi-asserted-by":"publisher","first-page":"509","DOI":"10.3928\/0048-5713-20020901-06","volume":"32","author":"K Kroenke","year":"2002","unstructured":"Kroenke, K. & Spitzer, R. L. The PHQ-9: A new depression diagnostic and severity measure. Psychiatr. Ann. 32, 509\u2013515 (2002).","journal-title":"Psychiatr. Ann."},{"key":"98067_CR80","doi-asserted-by":"publisher","first-page":"8430","DOI":"10.3402\/ejpt.v2i0.8430","volume":"2","author":"R Weierstall","year":"2011","unstructured":"Weierstall, R. & Elbert, T. The appetitive aggression scale\u2014development of an instrument for the assessment of human\u2019s attraction to violence. Eur. J. Psychotraumatol. 2, 8430 (2011).","journal-title":"Eur. J. Psychotraumatol."},{"key":"98067_CR81","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1177\/2167702614534239","volume":"3","author":"A Crombach","year":"2015","unstructured":"Crombach, A. & Elbert, T. Controlling offensive behavior using narrative exposure therapy: A randomized controlled trial of former street children. Clin. Psychol. Sci. 3, 270\u2013282 (2015).","journal-title":"Clin. Psychol. Sci."},{"key":"98067_CR82","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1007\/BF02229056","volume":"17","author":"ES Kubany","year":"1995","unstructured":"Kubany, E. S. et al. Initial examination of a multidimensional model of trauma-related guilt: Applications to combat veterans and battered women. J. Psychopathol. Behav. Assess. 17, 353\u2013376 (1995).","journal-title":"J. Psychopathol. Behav. Assess."},{"key":"98067_CR83","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1023\/B:JOTS.0000038484.15488.3d","volume":"17","author":"A Maercker","year":"2004","unstructured":"Maercker, A. & M\u00fcller, J. Social acknowledgment as a victim or survivor: A scale to measure a recovery factor of PTSD. J. Trauma. Stress 17, 345\u2013351 (2004).","journal-title":"J. Trauma. Stress"},{"key":"98067_CR84","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/j.fsigss.2019.10.034","volume":"7","author":"AM Burrows","year":"2019","unstructured":"Burrows, A. M., Kasu, M. & D\u2019Amato, M. E. Preservation of DNA integrity in biological material. Forens. Sci. Int. Genet. Suppl. Ser. 7, 416\u2013418 (2019).","journal-title":"Forens. Sci. Int. Genet. Suppl. Ser."},{"key":"98067_CR85","doi-asserted-by":"publisher","first-page":"3435","DOI":"10.1093\/bioinformatics\/btu566","volume":"30","author":"M van Iterson","year":"2014","unstructured":"van Iterson, M. et al. MethylAid: visual and interactive quality control of large Illumina 450k datasets. Bioinformatics 30, 3435\u20133437 (2014).","journal-title":"Bioinformatics"},{"key":"98067_CR86","doi-asserted-by":"publisher","first-page":"3156","DOI":"10.1186\/gb-2013-14-10-r115","volume":"14","author":"S Horvath","year":"2013","unstructured":"Horvath, S. DNA methylation age of human tissues and cell types. Genome Biol. 14, 3156 (2013).","journal-title":"Genome Biol."},{"key":"98067_CR87","unstructured":"Suderman, M., Hemani, G. & Min, J. meffil: efficient algorithms for DNA methylation. R package version 1.1.1. https:\/\/github.com\/perishky\/meffil. (2020)."},{"key":"98067_CR88","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","volume":"2","author":"Y Benjamini","year":"1995","unstructured":"Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: A practical and powerful approach to multiple testing. J. R. Stat. Soc. Ser. B 2, 289\u2013300 (1995).","journal-title":"J. R. Stat. Soc. Ser. B"},{"key":"98067_CR89","unstructured":"lme4: mixed-effects modeling with R (Berlin, 2010)."},{"key":"98067_CR90","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).","journal-title":"Nucleic Acids Res."},{"key":"98067_CR91","unstructured":"R: a language and environment for statistical computing (R Foundation for Statistical Computing, Vienna, Austria, 2018)."},{"key":"98067_CR92","unstructured":"RStudio: integrated development for R. RStudio, Inc., Boston, MA. URL: https:\/\/www.rstudio.com (2019)."},{"key":"98067_CR93","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1093\/bioinformatics\/btu049","volume":"30","author":"MJ Aryee","year":"2014","unstructured":"Aryee, M. J. et al. minfi: A flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics 30, 1363\u20131369. https:\/\/doi.org\/10.1093\/bioinformatics\/btu049 (2014).","journal-title":"Bioinformatics"},{"key":"98067_CR94","first-page":"e22","volume":"45","author":"W Zhou","year":"2017","unstructured":"Zhou, W., Laird, P. W. & Shen, H. Comprehensive characterization, annotation and innovative use of Infinium DNA methylation BeadChip probes. Nucleic Acids Res. 45, e22\u2013e22 (2017).","journal-title":"Nucleic Acids Res."},{"key":"98067_CR95","doi-asserted-by":"publisher","first-page":"D607","DOI":"10.1093\/nar\/gky1131","volume":"47","author":"D Szklarczyk","year":"2019","unstructured":"Szklarczyk, D. et al. STRING v11: Protein\u2013protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 47, D607\u2013D613 (2019).","journal-title":"Nucleic Acids Res."},{"key":"98067_CR96","doi-asserted-by":"publisher","first-page":"1789323","DOI":"10.1080\/20008198.2020.1789323","volume":"11","author":"A Schneider","year":"2020","unstructured":"Schneider, A. et al. Does cumulative exposure to traumatic stressors predict treatment outcome of community-implemented exposure-based therapy for PTSD?. Eur. J. Psychotraumatol. 11, 1789323 (2020).","journal-title":"Eur. J. Psychotraumatol."},{"key":"98067_CR97","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41398-020-00899-y","volume":"10","author":"V Vukojevic","year":"2020","unstructured":"Vukojevic, V. et al. Evolutionary conserved role of neural cell adhesion molecule-1 in memory. Transl. Psychiatry 10, 1\u201313 (2020).","journal-title":"Transl. Psychiatry"},{"key":"98067_CR98","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1037\/pas0000258","volume":"28","author":"EB Foa","year":"2016","unstructured":"Foa, E. B. et al. Psychometric properties of the posttraumatic diagnostic scale for DSM\u20135 (PDS\u20135). Psychol. Assess. 28, 1166 (2016).","journal-title":"Psychol. Assess."},{"key":"98067_CR99","first-page":"79","volume-title":"Psychological Measurements in Psychopharmacology","author":"LR Derogatis","year":"1974","unstructured":"Derogatis, L. R., Lipman, R. S., Rickels, K., Uhlenhuth, E. H. & Covi, L. In Psychological Measurements in Psychopharmacology Vol. 7 (eds Pichot, P. & Olivier-Martin, R.) 79\u2013110 (Karger, 1974)."},{"key":"98067_CR100","doi-asserted-by":"publisher","first-page":"28306","DOI":"10.3402\/ejpt.v6.28306","volume":"6","author":"S Wilker","year":"2015","unstructured":"Wilker, S. et al. How to quantify exposure to traumatic stress? Reliability and predictive validity of measures for cumulative trauma exposure in a post-conflict population. Eur. J. Psychotraumatol. 6, 28306 (2015).","journal-title":"Eur. J. Psychotraumatol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-98067-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-98067-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-98067-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,8]],"date-time":"2024-09-08T13:00:27Z","timestamp":1725800427000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-98067-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,16]]},"references-count":100,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["98067"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-98067-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,16]]},"assertion":[{"value":"7 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 September 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 September 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18493"}}