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To study predisposing effects of mild ELS on stress sensitivity, we examined in a healthy human population the impact of a history of ELS on acute stress\u2010related changes in corticolimbic circuits involved in emotional processing (i.e., amygdala, hippocampus and ventromedial prefrontal cortex [vmPFC]). Healthy young male participants (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009120) underwent resting\u2010state functional magnetic resonance imaging (fMRI) in two separate sessions (stress induction vs. control). The Childhood Trauma Questionnaire (CTQ) was administered to index self\u2010reported ELS, and stress induction was verified using salivary cortisol, blood pressure, heart rate and subjective affect. Our findings show that self\u2010reported ELS was negatively associated with baseline cortisol, but not with the acute stress\u2010induced cortisol response. Critically, individuals with more self\u2010reported ELS exhibited an exaggerated reduction of functional connectivity in corticolimbic circuits under acute stress. A mediation analysis showed that the association between ELS and stress\u2010induced changes in amygdala\u2013hippocampal connectivity became stronger when controlling for basal cortisol. Our findings show, in a healthy sample, that the effects of mild ELS on functioning of corticolimbic circuits only become apparent when exposed to an acute stressor and may be buffered by adaptations in hypothalamic\u2013pituitary\u2013adrenal axis function. Overall, our findings might reveal a potential mechanism whereby even mild ELS might confer vulnerability to exposure to stressors later in adulthood.\n                  <\/jats:p>","DOI":"10.1111\/ejn.15538","type":"journal-article","created":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T20:56:08Z","timestamp":1637614568000},"page":"2122-2141","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Mild early\u2010life stress exaggerates the impact of acute stress on corticolimbic resting\u2010state functional connectivity"],"prefix":"10.1111","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7598-6247","authenticated-orcid":false,"given":"Huan","family":"Wang","sequence":"first","affiliation":[{"name":"Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center, Radboud University  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7105-0038","authenticated-orcid":false,"given":"Judith M. C.","family":"van Leeuwen","sequence":"additional","affiliation":[{"name":"Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center, Radboud University  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lycia D.","family":"de Voogd","sequence":"additional","affiliation":[{"name":"Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center, Radboud University  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robbert\u2010Jan","family":"Verkes","sequence":"additional","affiliation":[{"name":"Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center, Radboud University  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7013-2111","authenticated-orcid":false,"given":"Benno","family":"Roozendaal","sequence":"additional","affiliation":[{"name":"Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center, Radboud University  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5522-0604","authenticated-orcid":false,"given":"Guill\u00e9n","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center, Radboud University  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1339-8639","authenticated-orcid":false,"given":"Erno J.","family":"Hermans","sequence":"additional","affiliation":[{"name":"Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center, Radboud University  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2013.05.005"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2018.01.020"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10608-014-9659-z"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2004.08.019"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-5215.2011.00610.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1961.01710120031004"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2016.01.016"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004583-199703000-00012"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2015.252"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/da.22291"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.150.2.235"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1440.011"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-017-0032-3"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3257"},{"key":"e_1_2_10_17_1","first-page":"20","volume-title":"Bodily changes in pain, hunger, fear, and rage, ed2","author":"Cannon W. 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