{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T09:01:46Z","timestamp":1785315706757,"version":"3.55.0"},"reference-count":46,"publisher":"Royal College of Psychiatrists","issue":"2","license":[{"start":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T00:00:00Z","timestamp":1738540800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MRC MR\/K002643\/1"],"award-info":[{"award-number":["MRC MR\/K002643\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Br J Psychiatry"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec id=\"S0007125024002599_sec_a1\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Anxiety symptoms are elevated among people with joint hypermobility. The underlying neural mechanisms are attributed theoretically to effects of variant connective tissue on the precision of interoceptive representations contributing to emotions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125024002599_sec_a2\">\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To investigate the neural correlates of anxiety and hypermobility using functional neuroimaging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125024002599_sec_a3\" sec-type=\"methods\">\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      We used functional magnetic resonance neuroimaging to quantify regional brain responses to emotional stimuli (facial expressions) in people with generalised anxiety disorder (GAD) (\n                      <jats:italic>N<\/jats:italic>\n                      = 30) and a non-anxious comparison group (\n                      <jats:italic>N<\/jats:italic>\n                      = 33). All participants were assessed for joint laxity and were classified (using Brighton Criteria) for the presence and absence of hypermobility syndrome (HMS: now considered hypermobility spectrum disorder).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125024002599_sec_a4\" sec-type=\"results\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Participants with HMS showed attenuated neural reactivity to emotional faces in specific frontal (inferior frontal gyrus, pre-supplementary motor area), midline (anterior mid and posterior cingulate cortices) and parietal (precuneus and supramarginal gyrus) regions. Notably, interaction between HMS and anxiety was expressed in reactivity of the left amygdala (a region implicated in threat processing) and mid insula (primary interoceptive cortex) where activity was amplified in people with HMS with GAD. Severity of hypermobility in anxious, compared with non-anxious, individuals correlated with activity within the anterior insula (implicated as the neural substrate linking anxious feelings to physiological state). Amygdala-precuneus functional connectivity was stronger in participants with HMS, compared with non-HMS participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125024002599_sec_a5\" sec-type=\"conclusions\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The predisposition to anxiety in people with variant connective tissue reflects dynamic interactions between neural centres processing threat (amygdala) and representing bodily state (insular and parietal cortices). Correspondingly, interventions to regulate amygdala reactivity while enhancing interoceptive precision may have therapeutic benefit for symptomatic hypermobile individuals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1192\/bjp.2024.259","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T02:32:21Z","timestamp":1738549941000},"page":"101-107","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":2,"title":["Neural processes linking joint hypermobility and anxiety: key roles for the amygdala and insular cortex"],"prefix":"10.1192","volume":"228","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4311-2830","authenticated-orcid":false,"given":"Christina N.","family":"Kampoureli","sequence":"first","affiliation":[{"name":"Brighton & Sussex Medical School"},{"name":"University of Sussex"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4503-4971","authenticated-orcid":false,"given":"Charlotte L.","family":"Rae","sequence":"additional","affiliation":[{"name":"University of Sussex"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8584-4637","authenticated-orcid":false,"given":"Cassandra","family":"Gould Van Praag","sequence":"additional","affiliation":[{"name":"The Alan Turing Institute, British Library"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9584-3769","authenticated-orcid":false,"given":"Neil A.","family":"Harrison","sequence":"additional","affiliation":[{"name":"University of Cardiff"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5961-1012","authenticated-orcid":false,"given":"Sarah N.","family":"Garfinkel","sequence":"additional","affiliation":[{"name":"University College London, London"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2445-9284","authenticated-orcid":false,"given":"Hugo D.","family":"Critchley","sequence":"additional","affiliation":[{"name":"Brighton & Sussex Medical School"},{"name":"Sussex Partnership NHS Foundation Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0062-1216","authenticated-orcid":false,"given":"Jessica A.","family":"Eccles","sequence":"additional","affiliation":[{"name":"Brighton & Sussex Medical School"},{"name":"Sussex Partnership NHS Foundation Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"170","published-online":{"date-parts":[[2025,2,3]]},"reference":[{"key":"S0007125024002599_ref31","doi-asserted-by":"publisher","DOI":"10.1038\/nrn894"},{"key":"S0007125024002599_ref19","first-page":"22","article-title":"The Mini-international neuropsychiatric interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10","volume":"59","author":"Sheehan","year":"1998","journal-title":"J Clin Psychiatry"},{"key":"S0007125024002599_ref20","doi-asserted-by":"publisher","DOI":"10.1136\/ard.32.5.413"},{"key":"S0007125024002599_ref42","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2021.101042"},{"key":"S0007125024002599_ref27","unstructured":"27 MATLAB. The MathWorks Inc, 2018."},{"key":"S0007125024002599_ref6","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2021.786916"},{"key":"S0007125024002599_ref39","doi-asserted-by":"publisher","DOI":"10.1016\/j.cortex.2014.08.017"},{"key":"S0007125024002599_ref29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1602413113"},{"key":"S0007125024002599_ref41","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-008-0077-9"},{"key":"S0007125024002599_ref30","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2007.03.060"},{"key":"S0007125024002599_ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.03.042"},{"key":"S0007125024002599_ref24","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-8119(09)72001-4"},{"key":"S0007125024002599_ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpr.2009.08.008"},{"key":"S0007125024002599_ref7","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keh279"},{"key":"S0007125024002599_ref44","doi-asserted-by":"publisher","DOI":"10.1017\/S1092852923002420"},{"key":"S0007125024002599_ref38","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-020-0790-9"},{"key":"S0007125024002599_ref28","doi-asserted-by":"publisher","DOI":"10.1089\/brain.2012.0073"},{"key":"S0007125024002599_ref3","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31539"},{"key":"S0007125024002599_ref4","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ket317"},{"key":"S0007125024002599_ref22","doi-asserted-by":"publisher","DOI":"10.1037\/0022-006X.56.6.893"},{"key":"S0007125024002599_ref2","first-page":"1777","article-title":"The revised (Brighton 1998) criteria for the diagnosis of benign joint hypermobility syndrome (BJHS)","volume":"27","author":"Grahame","year":"2000","journal-title":"J Rheumatol"},{"key":"S0007125024002599_ref21","doi-asserted-by":"publisher","DOI":"10.1002\/art.30435"},{"key":"S0007125024002599_ref34","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31957"},{"key":"S0007125024002599_ref15","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.111.092460"},{"key":"S0007125024002599_ref11","doi-asserted-by":"publisher","DOI":"10.5498\/wjp.v11.i10.805"},{"key":"S0007125024002599_ref23","volume-title":"IBM SPSS Statistics","year":"2022"},{"key":"S0007125024002599_ref8","first-page":"158","article-title":"Joint hypermobility syndrome and dysautonomia: expanding spectrum of disease presentation and manifestation","volume":"10","author":"Bohora","year":"2010","journal-title":"Indian Pacing Electrophysiol J"},{"key":"S0007125024002599_ref46","first-page":"8","article-title":"Neurovault.org: a web-based repository for collecting and sharing unthresholded statistical maps of the human brain","volume":"9","author":"Hill","year":"2015","journal-title":"Front Neuroinf"},{"key":"S0007125024002599_ref5","doi-asserted-by":"publisher","DOI":"10.1186\/s12888-016-0922-6"},{"key":"S0007125024002599_ref43","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-021-05555-4"},{"key":"S0007125024002599_ref25","doi-asserted-by":"publisher","DOI":"10.1080\/02699930701626582"},{"key":"S0007125024002599_ref26","volume-title":"Statistical Parametric Mapping: The Analysis of Functional Brain Images","author":"Penny","year":"2007"},{"key":"S0007125024002599_ref37","doi-asserted-by":"publisher","DOI":"10.31887\/DCNS.2017.19.2\/gfonzo"},{"key":"S0007125024002599_ref9","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2011.187"},{"key":"S0007125024002599_ref16","doi-asserted-by":"publisher","DOI":"10.1186\/2045-5380-3-7"},{"key":"S0007125024002599_ref14","first-page":"1162","article-title":"Neuroimaging and psychophysiological investigation of the link between anxiety, enhanced affective reactivity and interoception in people with joint hypermobility","volume":"5","author":"Mallorqu\u00ed-Bagu\u00e9","year":"2014","journal-title":"Front Psychol"},{"key":"S0007125024002599_ref36","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2020.07.004"},{"key":"S0007125024002599_ref45","doi-asserted-by":"publisher","DOI":"10.1016\/j.ssmqr.2023.100237"},{"key":"S0007125024002599_ref10","first-page":"4","article-title":"Neurovisceral phenotypes in the expression of psychiatric symptoms","volume":"10","author":"Eccles","year":"2015","journal-title":"Front Neurosci"},{"key":"S0007125024002599_ref18","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.2007.164.2.318"},{"key":"S0007125024002599_ref35","doi-asserted-by":"publisher","DOI":"10.1111\/bdi.13341"},{"key":"S0007125024002599_ref40","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3507-13.2014"},{"key":"S0007125024002599_ref17","doi-asserted-by":"publisher","DOI":"10.1139\/jpn.0939"},{"key":"S0007125024002599_ref33","doi-asserted-by":"publisher","DOI":"10.1016\/j.copsyc.2017.04.020"},{"key":"S0007125024002599_ref32","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2555"},{"key":"S0007125024002599_ref1","volume-title":"Hypermobility Syndrome","author":"Keer","year":"2003"}],"container-title":["The British Journal of Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0007125024002599","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T08:31:06Z","timestamp":1785313866000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0007125024002599\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,3]]},"references-count":46,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["S0007125024002599"],"URL":"https:\/\/doi.org\/10.1192\/bjp.2024.259","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.10.10.24315234","asserted-by":"object"}]},"ISSN":["0007-1250","1472-1465"],"issn-type":[{"value":"0007-1250","type":"print"},{"value":"1472-1465","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,3]]},"assertion":[{"value":"\u00a9 The Author(s), 2025. Published by Cambridge University Press on behalf of Royal College of Psychiatrists","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"}]}}