{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:37:40Z","timestamp":1792798660456,"version":"4.5.0"},"reference-count":49,"publisher":"BMJ","issue":"10","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"unspecified","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Fondation Force University Hospital of Strasbourg","id":[{"id":"https:\/\/ror.org\/04bckew43","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100020320","name":"Institut pour la Recherche en Sant\u00e9 Publique","doi-asserted-by":"publisher","award":["IIRESP-AAPSPA2021-V1-03"],"award-info":[{"award-number":["IIRESP-AAPSPA2021-V1-03"]}],"id":[{"id":"10.13039\/501100020320","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Agence R\u00e9gionale de Sant\u00e9 Grand Est"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,9,16]]},"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Opioid use disorder (OUD) is a chronic and severe psychiatric condition defined by a level of opioid use which significantly impairs interpersonal and social functioning. In the biopsychosocial model of addiction, research has shown that psychiatric, sociological and neurobiological factors individually affect OUD severity. However, how these factors interact in the determination of OUD severity remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method and analysis<\/jats:title>\n                    <jats:p>The Epigenetic Bonds of Opioid Use Profiles are a multidisciplinary project whose primary objective is to characterise psychiatric and social factors of OUD in a large cohort of patients. The secondary objectives are, first, to correlate psychosocial severity with blood-derived epigenetic biomarkers to provide a deeper understanding of determinants of OUD and, second, to examine over a 2\u2009year follow-up the correlation between the evolution of OUD and psychosocial severity with epigenetic biomarkers at inclusion. An additional objective is to analyse the impact of drug consumption rooms on access to care for most severely affected patients with OUD. In total, 300 opioid users will be recruited at supervised injection sites in Strasbourg and Paris and at addiction care centres in Strasbourg and Lyon to explore four psychiatric (substance use disorders beyond opioids, depression, anxiety, post-traumatic stress disorder) and five social (social support and status, traumatic experiences, housing, imprisonment, access to care) factors. Opioid users will be followed for 24 months and reassessed for psychosocial factors at 3, 6, 12, 18 and 24 months. Opioid consumption will be measured in all subjects using questionnaires, complemented by toxicological screenings (mass spectrometry). Finally, DNA methylation and gene expression will be characterised in capillary blood using next-generation sequencing. Mixed models will be used to model the primary and secondary outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This ongoing study was approved by the French Ethics Committee \u2018Sud M\u00e9diterran\u00e9e III\u2019 of University Hospital of N\u00eemes (approval 2023\u20132024, protocol IDRCB number 2022-A02477-36) and authorised by the French Data Protection Authority (authorisation decision DR-2023\u2013277 in December 2023). Results will be presented in international and national conferences and published in peer-reviewed international journals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT06021548\">NCT06021548<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-093358","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T16:15:14Z","timestamp":1760372114000},"page":"e093358","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Integrative exploration of bio-psycho-social determinants of DSM-5 severity levels of opioid use disorder: the BEBOP cohort study 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