{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:53:06Z","timestamp":1785405186163,"version":"3.56.0"},"reference-count":29,"publisher":"Cambridge University Press (CUP)","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"unspecified","delay-in-days":280,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100009077","name":"ITEA3","doi-asserted-by":"publisher","award":["21016"],"award-info":[{"award-number":["21016"]}],"id":[{"id":"10.13039\/501100009077","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Psychol. Med."],"published-print":{"date-parts":[[2025]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"S0033291725101797_sec1\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Heightened reactivity in the amygdala measured by functional magnetic resonance imaging during emotional processing is considered a potential biomarker for clinical depression. Still, it is unknown whether this is also true for depressive symptoms in the general population, and \u2013 when in remission after recurrent depressive episodes \u2013 it is associated with future episodes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291725101797_sec2\" sec-type=\"methods\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using the UK Biobank population study (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a011,334), we investigated the association of amygdala reactivity during negative facial stimuli, focusing on lifetime depression (trait), depressive symptoms (state), and the modulating effect of antidepressant (AD) treatment thereof. We employed normative modeling (NM) to better incorporate population heterogeneity of the amygdala activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291725101797_sec3\" sec-type=\"results\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In line with a previous study, depressive symptoms (state) over the last 2 weeks were not associated with the amygdala reactivity signal. Rather, our results indicate a significant positive association (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.03,\n                      <jats:italic>\u03c9<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a00.001) between amygdala response and the recurrence of depressive episodes (trait). Longitudinal analysis revealed that the group that had experienced a single depressive episode before showed a significantly increased amygdala response after additional episodes (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.03,\n                      <jats:italic>\u03c9<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a00.017). ADs were not associated with amygdala response directly, but decreased associations within episode recurrence severity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291725101797_sec4\" sec-type=\"conclusions\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The amygdala response to negative stimuli was associated with an individual\u2019s risk of recurrence of depressive episodes, and AD treatment reduced these associations. This study highlights the relevance of amygdala reactivity as a trait, but not a state biomarker for (recurrent) depression. Moreover, it demonstrates the benefit of applying NM in the context of population data.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1017\/s0033291725101797","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:16:28Z","timestamp":1759918588000},"update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":2,"title":["Normative amygdala fMRI response during emotional processing as a trait of depressive symptoms in the UK Biobank"],"prefix":"10.1017","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2124-9721","authenticated-orcid":false,"given":"Jerke J.","family":"van den Berg","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03t4gr691","id-type":"ROR","asserted-by":"publisher"}],"name":"Amsterdam UMC Location AMC, University of Amsterdam"},{"id":[{"id":"https:\/\/ror.org\/03t4gr691","id-type":"ROR","asserted-by":"publisher"}],"name":"Amsterdam UMC Location AMC, University of Amsterdam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6072-0358","authenticated-orcid":false,"given":"Henricus G.","family":"Ruh\u00e9","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01yb10j39","id-type":"ROR","asserted-by":"publisher"}],"name":"Radboud UMC"},{"name":"Radboud University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1414-6313","authenticated-orcid":false,"given":"Henk A.","family":"Marquering","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03t4gr691","id-type":"ROR","asserted-by":"publisher"}],"name":"Amsterdam UMC Location AMC, University of Amsterdam"},{"id":[{"id":"https:\/\/ror.org\/03t4gr691","id-type":"ROR","asserted-by":"publisher"}],"name":"Amsterdam UMC Location AMC, University of Amsterdam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5912-9971","authenticated-orcid":false,"given":"Liesbeth","family":"Reneman","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03t4gr691","id-type":"ROR","asserted-by":"publisher"}],"name":"Amsterdam UMC Location AMC, University of Amsterdam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5162-8880","authenticated-orcid":false,"given":"Matthan W. A.","family":"Caan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03t4gr691","id-type":"ROR","asserted-by":"publisher"}],"name":"Amsterdam UMC Location AMC, University of Amsterdam"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"S0033291725101797_r1","unstructured":"Dunlop, B. W. , & Mayberg, H. S. (2017). Neuroimaging advances for depression. 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Published by Cambridge University Press","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http:\/\/creativecommons.org\/licenses\/by\/4.0), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}],"article-number":"e304"}}