{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T23:13:47Z","timestamp":1793402027897,"version":"4.5.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T00:00:00Z","timestamp":1619395200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T00:00:00Z","timestamp":1619395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004189","name":"Max-Planck-Gesellschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004189","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Psychiatry"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In search of the neural basis of severe trauma exposure and post-traumatic stress disorder (PTSD), a multitude of cross-sectional studies have been conducted, most of them pointing at structural deficits in the hippocampus and medial prefrontal cortex including the anterior cingulate cortex (ACC) and ventromedial prefrontal cortex (vmPFC). Since cross-sectional studies are silent to causality, the core question remains: which brain structural alterations constitute a risk factor for disease and therewith precede the stressor, and which brain regions may undergo alterations as a consequence of exposure to the stressor. We assessed 121 soldiers before and after deployment to regions of war and 40 soldiers as controls, who were not deployed. Analysis using voxel-based morphometry revealed volumetric reductions in the ACC, vmPFC (region of interest analysis, effect does not survive conservative multiple test correction) and in bilateral thalamus (whole-brain analysis) in the deployment group. Remarkably, the ACC and vmPFC volume decrease was not limited to the period of deployment, but continued over the following 6 months after deployment. Volumetric reductions did not correlate with increases in PTSD symptoms. The volume decreases in medial prefrontal cortex and thalamus seem to be driven by trauma exposure rather than a vulnerability factor for PTSD. However, data indicate that the volume decrease in medial prefrontal cortex surpasses the time period of deployment. This may hint at an initiated pathobiological process below a symptom threshold, potentially paving the way to future mental health problems.<\/jats:p>","DOI":"10.1038\/s41398-021-01356-0","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T16:05:06Z","timestamp":1619453106000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["The brain at war: effects of stress on brain structure in soldiers deployed to a war zone"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6823-7969","authenticated-orcid":false,"given":"Simone","family":"K\u00fchn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oisin","family":"Butler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2267-6389","authenticated-orcid":false,"given":"Gerd","family":"Willmund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2537-2148","authenticated-orcid":false,"given":"Ulrich","family":"Wesemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Zimmermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Gallinat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,26]]},"reference":[{"key":"1356_CR1","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1038\/138032a0","volume":"138","author":"H Selye","year":"1936","unstructured":"Selye, H. A syndrome produced by diverse nocuous agents. Nature 138, 32 (1936).","journal-title":"Nature"},{"key":"1356_CR2","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1038\/s41380-019-0383-7","volume":"24","author":"G Rakesh","year":"2019","unstructured":"Rakesh, G. et al. Resilience as a translational endpoint in the treatment of PTSD. Mol. Psychiatry 24, 1268\u201383 (2019).","journal-title":"Mol. Psychiatry"},{"key":"1356_CR3","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1056\/NEJMsa013404","volume":"346","author":"S Galea","year":"2002","unstructured":"Galea, S. et al. Psychological sequelae of the September 11 terrorist attacks in New York City. N. Engl. J. Med. 346, 982\u2013987 (2002).","journal-title":"N. Engl. J. Med."},{"key":"1356_CR4","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.biopsych.2012.06.029","volume":"73","author":"S K\u00fchn","year":"2013","unstructured":"K\u00fchn, S. & Gallinat, J. Gray matter correlates of posttraumatic stress disorder: a quantitative meta-analysis. Biol. Psychiatry 73, 70\u201374 (2013).","journal-title":"Biol. Psychiatry"},{"key":"1356_CR5","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.neubiorev.2014.04.003","volume":"43","author":"L Li","year":"2014","unstructured":"Li, L. et al. Grey matter reduction associated with posttraumatic stress disorder and traumatic stress. Neurosci. Biobehav. Rev. 43, 163\u201372 (2014).","journal-title":"Neurosci. Biobehav. Rev."},{"key":"1356_CR6","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1001\/archgenpsychiatry.2011.70","volume":"68","author":"IK Lyoo","year":"2011","unstructured":"Lyoo, I. K. et al. The neurobiological role of the dorsolateral prefrontal cortex in recovery from trauma. Longitudinal brain imaging study among survivors of the South Korean subway disaster. Arch. Gen. Psychiatry 68, 701\u201313 (2011).","journal-title":"Arch. Gen. Psychiatry"},{"key":"1356_CR7","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1176\/appi.ajp.158.8.1248","volume":"158","author":"O Bonne","year":"2001","unstructured":"Bonne, O. et al. Longitudinal MRI study of hippocampal volume in trauma survivors with PTSD. Am. J. Psychiatry 158, 1248\u201351 (2001).","journal-title":"Am. J. Psychiatry"},{"key":"1356_CR8","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1038\/nn958","volume":"5","author":"MW Gilbertson","year":"2002","unstructured":"Gilbertson, M. W. et al. Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma. Nat. Neurosci. 5, 1242\u20131247 (2002).","journal-title":"Nat. Neurosci."},{"key":"1356_CR9","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1016\/j.biopsych.2007.06.022","volume":"63","author":"K Kasai","year":"2008","unstructured":"Kasai, K. et al. Evidence for acquired pregenual anterior cingulate gray matter loss from a twin study of combat-related posttraumatic stress disorder. Biol. Psychiatry 63, 550\u2013556 (2008).","journal-title":"Biol. Psychiatry"},{"key":"1356_CR10","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/j.neuropharm.2011.03.012","volume":"62","author":"WS Kremen","year":"2012","unstructured":"Kremen, W. S., Koenen, K. C., Afari, N. & Lyons, M. J. Twin studies of posttraumatic stress disorder: differentiating vulnerability factors from sequelae. Neuropharmacology 62, 647\u201353 (2012).","journal-title":"Neuropharmacology"},{"key":"1356_CR11","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1038\/mp.2010.132","volume":"16","author":"GA van Wingen","year":"2011","unstructured":"van Wingen, G. A., Geuze, E., Vermetten, E. & Fernandez, G. Perceived threat predicts the neural sequelae of combat stress. Mol. Psychiatry 16, 664\u201371 (2011).","journal-title":"Mol. Psychiatry"},{"key":"1356_CR12","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1038\/mp.2011.110","volume":"17","author":"GA van Wingen","year":"2012","unstructured":"van Wingen, G. A., Geuze, E., Vermetten, E. & Fernandez, G. The neural consequences of combat stress: long-term follow-up. Mol. Psychiatry 17, 116\u2013118 (2012).","journal-title":"Mol. Psychiatry"},{"key":"1356_CR13","doi-asserted-by":"publisher","first-page":"15508","DOI":"10.1073\/pnas.1206330109","volume":"109","author":"GA van Wingen","year":"2012","unstructured":"van Wingen, G. A. et al. Persistent and reversible consequences of combat stress on the mesofrontal circuit and cognition. Proc. Natl Acad. Sci. USA 109, 15508\u201313 (2012).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1356_CR14","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1038\/mp.2014.28","volume":"20","author":"A Sekiguchi","year":"2015","unstructured":"Sekiguchi, A. et al. Resilience after 3\/11: structural brain changes 1 year after the Japanese earthquake. Mol. Psychiatry 20, 553\u2013554 (2015).","journal-title":"Mol. Psychiatry"},{"key":"1356_CR15","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1037\/1040-3590.9.4.445","volume":"9","author":"EB Foa","year":"1997","unstructured":"Foa, E. B., Cashman, L., Jaycox, L. & Perry, K. The validation of a self-report measure of posttraumatic stress disorder: The Posttraumatic Diagnostic Scale. Psychological Assess. 9, 445 (1997).","journal-title":"Psychological Assess."},{"key":"1356_CR16","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-5 (PDS-5). Psychol. Assess. 28, 1166\u201371 (2016).","journal-title":"Psychol. Assess."},{"key":"1356_CR17","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1080\/08897077.2014.891555","volume":"35","author":"LE Winters","year":"2014","unstructured":"Winters, L. E. et al. Psychometric properties of the Posttraumatic Diagnostic Scale (PDS) in alcohol-dependent patients. Subst. Abus. 35, 262\u2013267 (2014).","journal-title":"Subst. Abus."},{"key":"1356_CR18","doi-asserted-by":"publisher","first-page":"464","DOI":"10.3758\/s13428-019-01246-w","volume":"52","author":"P Mair","year":"2020","unstructured":"Mair, P. & Wilcox, R. Robust statistical methods in R using the WRS2 package. Behav. Res. Methods 52, 464\u201388 (2020).","journal-title":"Behav. Res. Methods"},{"key":"1356_CR19","unstructured":"Brett, M, Anton, J.-C., Valabreuge, R & Poline, J. B. Region of interest analysis using an SPM toolbox. Presented at the 8th International Conference on Functional Mapping of the Human Brain, Sendai, Japan (2002)."},{"key":"1356_CR20","doi-asserted-by":"crossref","unstructured":"Tzourio-Mazoyer, N. et al. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage 15, 273\u2013289 (2002).","DOI":"10.1006\/nimg.2001.0978"},{"key":"1356_CR21","doi-asserted-by":"crossref","unstructured":"Hayasaka, S. & Nichols, T. E. Combining voxel intensity and cluster extent with permutation test framework. NeuroImage 23, 54\u201363 (2004).","DOI":"10.1016\/j.neuroimage.2004.04.035"},{"key":"1356_CR22","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/s10862-012-9309-2","volume":"35","author":"J Roelofs","year":"2012","unstructured":"Roelofs, J. et al. Norms for the Beck Depression Inventory (BDI-II) in a large Dutch community sample. J. Psychopathol. Behav. Assess. 35, 93\u201398 (2012).","journal-title":"J. Psychopathol. Behav. Assess."},{"key":"1356_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.288","volume":"7","author":"O Butler","year":"2017","unstructured":"Butler, O. et al. Military deployment correlates with smaller prefrontal gray matter volume and psychological symptoms in a subclinical population. Transl. Psychiatry 7, e1031 (2017).","journal-title":"Transl. Psychiatry"},{"key":"1356_CR24","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.psychres.2017.08.028","volume":"258","author":"N R\u00fcsch","year":"2017","unstructured":"R\u00fcsch, N. et al. Attitudes towards disclosing a mental illness among German soldiers and their comrades. Psychiatry Res. 258, 200\u2013206 (2017).","journal-title":"Psychiatry Res."},{"key":"1356_CR25","first-page":"559","volume":"109","author":"HU Wittchen","year":"2012","unstructured":"Wittchen, H. U. et al. Traumatic experiences and posttraumatic stress disorder in soldiers following deployment abroad: how big is the hidden problem? Dtsch. Arztebl. Int. 109, 559\u201368 (2012).","journal-title":"Dtsch. Arztebl. Int."},{"key":"1356_CR26","doi-asserted-by":"publisher","first-page":"134","DOI":"10.21706\/tg-12-2-134","volume":"12","author":"P Zimmermann","year":"2018","unstructured":"Zimmermann, P. et al. Depressivit\u00e4t und Wert\u00adorientierungen im Verlauf von milit\u00e4rischen Auslands\u00adeins\u00e4tzen. Trauma und Gewalt 12, 134\u201350 (2018).","journal-title":"Trauma und Gewalt"},{"key":"1356_CR27","doi-asserted-by":"crossref","unstructured":"Papagni, S. A. et al. Effects of stressful life events on human brain structure: a longitudinal voxel-based morphometry study. Stress 14, 227\u2013232 (2011).","DOI":"10.3109\/10253890.2010.522279"},{"key":"1356_CR28","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1093\/cercor\/bhi104","volume":"16","author":"JJ Radley","year":"2006","unstructured":"Radley, J. J. et al. Repeated stress induces dendritic spine loss in the rat medial prefrontal cortex. Cereb. Cortex 16, 313\u201320 (2006).","journal-title":"Cereb. Cortex"},{"key":"1356_CR29","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1038\/mp.2012.51","volume":"18","author":"A Sekiguchi","year":"2013","unstructured":"Sekiguchi, A. et al. Brain structural changes as vulnerability factors and acquired signs of post-earthquake stress. Mol. Psychiatry 18, 618\u201323 (2013).","journal-title":"Mol. Psychiatry"},{"key":"1356_CR30","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1016\/j.biopsych.2006.06.004","volume":"60","author":"SL Rauch","year":"2006","unstructured":"Rauch, S. L., Shin, L. M. & Phelps, E. A. Neurocircuitry models of posttraumatic stress disorder and extinction: human neuroimaging research\u2013past, present, and future. Biol. Psychiatry 60, 376\u201382 (2006).","journal-title":"Biol. Psychiatry"},{"key":"1356_CR31","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.neuron.2016.09.039","volume":"92","author":"I Liberzon","year":"2016","unstructured":"Liberzon, I. & Abelson, J. L. Context processing and the neurobiology of post-traumatic stress disorder. Neuron 92, 14\u201330 (2016).","journal-title":"Neuron"},{"key":"1356_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pscychresns.2015.01.002","volume":"232","author":"DC O\u2019Doherty","year":"2015","unstructured":"O\u2019Doherty, D. C., Chitty, K. M., Saddiqui, S., Bennett, M. R. & Lagopoulos, J. A systematic review and meta-analysis of magnetic resonance imaging measurement of structural volumes in posttraumatic stress disorder. Psychiatry Res. 232, 1\u201333 (2015).","journal-title":"Psychiatry Res."},{"key":"1356_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-12917-z","volume":"7","author":"T Yoshii","year":"2017","unstructured":"Yoshii, T. et al. Brain atrophy in the visual cortex and thalamus induced by severe stress in animal model. Sci. Rep. 7, 12731 (2017).","journal-title":"Sci. Rep."},{"key":"1356_CR34","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.neubiorev.2016.09.028","volume":"71","author":"HC Bergstrom","year":"2016","unstructured":"Bergstrom, H. C. The neurocircuitry of remote cued fear memory. Neurosci. Biobehav. Rev. 71, 409\u201317 (2016).","journal-title":"Neurosci. Biobehav. Rev."},{"key":"1356_CR35","doi-asserted-by":"crossref","unstructured":"LeDoux, J. The emotional brain, fear, and the amygdala. Cell. Mol. Neurobiol. 23, 727\u2013738 (2003).","DOI":"10.1023\/A:1025048802629"},{"key":"1356_CR36","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.neuron.2019.03.017","volume":"102","author":"SA Maddox","year":"2019","unstructured":"Maddox, S. A., Hartmann, J., Ross, R. A. & Ressler, K. J. Deconstructing the Gestalt: mechanisms of fear, threat, and trauma memory encoding. Neuron 102, 60\u201374 (2019).","journal-title":"Neuron"},{"key":"1356_CR37","doi-asserted-by":"publisher","first-page":"e83967","DOI":"10.1371\/journal.pone.0083967","volume":"9","author":"A Sekiguchi","year":"2014","unstructured":"Sekiguchi, A. et al. White matter microstructural changes as vulnerability factors and acquired signs of post-earthquake distress. PLoS ONE 9, e83967 (2014).","journal-title":"PLoS ONE"},{"key":"1356_CR38","doi-asserted-by":"publisher","first-page":"157","DOI":"10.7205\/MILMED.172.2.157","volume":"172","author":"TM Greene-Shortridge","year":"2007","unstructured":"Greene-Shortridge, T. M., Britt, T. W. & Castro, C. A. The stigma of mental health problems in the military. Mil. Med. 172, 157\u201361 (2007).","journal-title":"Mil. Med."},{"key":"1356_CR39","doi-asserted-by":"crossref","unstructured":"Morey, R. D. Confidence intervals from normalized data: a correction to Cousineau (2005). Tutor. Quant. Methods Psychol. 4, 61\u201364 (2008).","DOI":"10.20982\/tqmp.04.2.p061"}],"container-title":["Translational Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41398-021-01356-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-021-01356-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-021-01356-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T08:01:28Z","timestamp":1669881688000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41398-021-01356-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,26]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["1356"],"URL":"https:\/\/doi.org\/10.1038\/s41398-021-01356-0","relation":{},"ISSN":["2158-3188"],"issn-type":[{"value":"2158-3188","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,26]]},"assertion":[{"value":"11 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 March 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 March 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 April 2021","order":4,"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":"Conflict of interest"}}],"article-number":"247"}}