{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:35:26Z","timestamp":1790804126200,"version":"4.1.0"},"reference-count":95,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T00:00:00Z","timestamp":1669161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["PP00P3_176985"],"award-info":[{"award-number":["PP00P3_176985"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Leenards Nested Project","award":["3642"],"award-info":[{"award-number":["3642"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Stress is a well-known risk factor to develop a functional neurological disorder, a frequent neuropsychiatric medical condition in which patients experience a variety of disabling neurological symptoms. Only little is known about biological stress regulation, and how it interacts with predisposing biological and psychosocial risk factors. Dysregulation of the hypothalamic\u2013pituitary\u2013adrenal axis in patients with functional neurological disorders has been postulated, but its relationship to preceding psychological trauma and brain anatomical changes remains to be elucidated. We set out to study the hypothalamic\u2013pituitary\u2013adrenal axis analysing the cortisol awakening response and diurnal baseline cortisol in 86 patients with mixed functional neurological symptoms compared to 76 healthy controls. We then examined the association between cortisol regulation and the severity and duration of traumatic life events. Finally, we analysed volumetric brain alterations in brain regions particularly sensitive to psychosocial stress, acting on the assumption of the neurotoxic effect of prolonged cortisol exposure.<\/jats:p>\n               <jats:p>Overall, patients had a significantly flatter cortisol awakening response (P &amp;lt; 0.001) and reported longer (P = 0.01) and more severe (P &amp;lt; 0.001) emotional neglect as compared to healthy controls. Moreover, volumes of the bilateral amygdala and hippocampus were found to be reduced in patients. Using a partial least squares correlation, we found that in patients, emotional neglect plays a role in the multivariate pattern between trauma history and hypothalamic\u2013pituitary\u2013adrenal axis dysfunction, while cortisol did not relate to reduced brain volumes. This suggests that psychological stress acts as a precipitating psychosocial risk factor, whereas a reduced brain volume rather represents a biological predisposing trait marker for the disorder. Contrarily, an inverse relationship between brain volume and cortisol was found in healthy controls, representing a potential neurotoxic effect of cortisol. These findings support the theory of reduced subcortical volumes representing a predisposing trait factor in functional neurological disorders, rather than a state effect of the illness. In summary, this study supports a stress\u2013diathesis model for functional neurological disorders and showed an association between different attributes of trauma history and abnormalities in hypothalamus\u2013pituitary\u2013adrenal axis function. Moreover, we suggest that reduced hippocampal and amygdalar volumes represent a biological \u2018trait marker\u2019 for functional neurological disorder patients, which might contribute to a reduced resilience to stress.<\/jats:p>","DOI":"10.1093\/brain\/awac442","type":"journal-article","created":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T18:39:45Z","timestamp":1669228785000},"page":"2627-2641","source":"Crossref","is-referenced-by-count":58,"title":["Identification of biopsychological trait markers in functional neurological disorders"],"prefix":"10.1093","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2689-2938","authenticated-orcid":false,"given":"Samantha","family":"Weber","sequence":"first","affiliation":[{"name":"Department of Neurology, Psychosomatic Medicine Unit, Inselspital Bern University Hospital, University of Bern , 3012 Bern , Switzerland"},{"name":"Translational Imaging Center (TIC), Swiss Institute for Translational and Entrepreneurial Medicine , 3010 Bern , Switzerland"},{"name":"Graduate School for Cellular and Biomedical Sciences (GCB), University of Bern , 3010 Bern , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0318-8371","authenticated-orcid":false,"given":"Janine","family":"B\u00fchler","sequence":"additional","affiliation":[{"name":"Department of Neurology, Psychosomatic Medicine Unit, Inselspital Bern University Hospital, University of Bern , 3012 Bern , Switzerland"},{"name":"Translational Imaging Center (TIC), Swiss Institute for Translational and Entrepreneurial Medicine , 3010 Bern , Switzerland"},{"name":"Graduate School for Health Sciences (GHS), University of Bern , 3012 Bern , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Vanini","sequence":"additional","affiliation":[{"name":"Department of Neurology, Psychosomatic Medicine Unit, Inselspital Bern University Hospital, University of Bern , 3012 Bern , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1878-7054","authenticated-orcid":false,"given":"Serafeim","family":"Loukas","sequence":"additional","affiliation":[{"name":"Department of Neurology, Psychosomatic Medicine Unit, Inselspital Bern University Hospital, University of Bern , 3012 Bern , Switzerland"},{"name":"Division of Development and Growth, Department of Pediatrics, University of Geneva , 1211 Geneva , Switzerland"},{"name":"Institute of Bioengineering, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL) , 1015 Lausanne , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9374-5890","authenticated-orcid":false,"given":"Rupert","family":"Bruckmaier","sequence":"additional","affiliation":[{"name":"Veterinary Physiology, Vetsuisse Faculty, University of Bern , 3012 Bern , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7877-6760","authenticated-orcid":false,"given":"Selma","family":"Aybek","sequence":"additional","affiliation":[{"name":"Department of Neurology, Psychosomatic Medicine Unit, Inselspital Bern University Hospital, University of Bern , 3012 Bern , Switzerland"},{"name":"Translational Imaging Center (TIC), Swiss Institute for Translational and Entrepreneurial Medicine , 3010 Bern , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,11,23]]},"reference":[{"key":"2023060100313089000_awac442-B1","first-page":"28","article-title":"A practical review of functional neurological disorder (FND) for the general physician","volume":"21","author":"Bennett","year":"2021","journal-title":"Clin Med J R Coll Physicians London"},{"key":"2023060100313089000_awac442-B2","first-page":"47","volume-title":"Handbook of clinical 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