{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T09:48:45Z","timestamp":1791625725673,"version":"4.3.4"},"reference-count":55,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Oral Rehabilitation"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Burning mouth syndrome (BMS) is a chronic, idiopathic and debilitating orofacial pain disorder, increasingly discussed within oral dysaesthesia and nociplastic pain frameworks, in which psychological distress and stress\u2010related mechanisms are frequently implicated. Vitamin B6, homocysteine and adrenocorticotropic hormone (ACTH) reflect biologically interconnected micronutrient, one\u2010carbon\u2010metabolic and neuroendocrine pathways, but their relevance to BMS and particularly their interrelationships within patients remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To compare plasma vitamin B6, homocysteine and ACTH concentrations between patients with BMS and controls, and to characterise the relationships among these biomarkers and with anxiety and depression within each group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this exploratory case\u2013control ancillary analysis of the OPIODYN study, plasma pyridoxal 5\u2032\u2010phosphate (PLP; vitamin B6), homocysteine and ACTH were measured in 21 patients with BMS and 17 controls, and anxiety and depression were assessed with the Hospital Anxiety and Depression Scale (HADS). Between\u2010group comparisons used 2\u2010sided Mann\u2013Whitney\n                      <jats:italic>U<\/jats:italic>\n                      tests with Hodges\u2013Lehmann median differences and 95% confidence intervals (CIs). Within\u2010group Spearman correlations and between\u2010group differences in correlation strength (\u0394\u03c1, Monte Carlo permutation) were computed, with Benjamini\u2013Hochberg control of the false discovery rate within pre\u2010declared families.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      No statistically significant between\u2010group differences were observed for PLP, homocysteine or ACTH concentrations. Median differences were +5.35\u2009nmol\/L (95% CI, \u221214.88 to 26.78;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.567) for PLP, \u22120.13\u2009\u03bcmol\/L (95% CI, \u22121.81 to 1.49;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.907) for homocysteine and \u22120.66\u2009pmol\/L (95% CI, \u22121.61 to 0.35;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.186) for ACTH. Most participants in both groups had adequate PLP and within\u2010range homocysteine and basal ACTH. Homocysteine and ACTH were strongly correlated in patients with BMS (\u03c1\u2009=\u20090.806; 95% CI 0.562\u20130.891) but not in controls (\u03c1\u2009=\u20090.204; 95% CI, \u22120.344 to 0.668), with a significant between\u2010group difference in correlation strength (\u0394\u03c1\u2009=\u20090.602;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.018). Among patients with BMS, both HADS subscales showed positive correlations with homocysteine and ACTH (\u03c1\u2009=\u20090.61\u20130.64; all\n                      <jats:italic>q<\/jats:italic>\n                      \u2009=\u20090.010), whereas no corresponding correlation was significant in controls, and PLP was not correlated with HADS or with the other biomarkers in either group. No single biomarker discriminated BMS from control status (AUC, 0.51\u20130.63).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These exploratory findings do not support vitamin B6, homocysteine, or ACTH as stand\u2010alone biomarkers of BMS. Rather, they suggest that psychological distress maps onto a homocysteine\u2013ACTH correlation axis in patients with BMS, from which PLP appears dissociated, and support a shift in BMS biomarker research from isolated concentrations towards the relationships among metabolic, neuroendocrine and affective dimensions. Larger studies are needed to test the reproducibility of this pattern and its potential value for identifying clinically meaningful BMS subgroups.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/joor.70253","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:54:22Z","timestamp":1783472062000},"page":"2053-2063","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of Vitamin\n                    <scp>B6<\/scp>\n                    and Homocysteine\u2013\n                    <scp>ACTH<\/scp>\n                    Coupling With Depressive and Anxiety Symptoms in Burning Mouth Syndrome: An Exploratory Case\u2013Control Study"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7869-3650","authenticated-orcid":false,"given":"Ashley","family":"Lebel","sequence":"first","affiliation":[{"name":"Department of Orofacial Pain Institute of Dental Surgery, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP)  Paris France"},{"name":"Gene Regulation and Adaptive Behaviors, Center for Neuroscience Sorbonne University (NeuroSU) UMR CNRS 8265, Inserm 1341, Sorbonne Universit\u00e9  Paris France"},{"name":"Laboratory of Orofacial Neurobiology, Inserm UMR 1333 Oral Health, Universit\u00e9 Paris Cit\u00e9  Montrouge France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8989-8229","authenticated-orcid":false,"given":"Charlotte","family":"Guillouet","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry Rothschild Hospital, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP)  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Porporatti","sequence":"additional","affiliation":[{"name":"Department of Orofacial Pain Institute of Dental Surgery, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP)  Paris France"},{"name":"Laboratory of Orofacial Neurobiology, Inserm UMR 1333 Oral Health, Universit\u00e9 Paris Cit\u00e9  Montrouge France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6182-0860","authenticated-orcid":false,"given":"Yves","family":"Boucher","sequence":"additional","affiliation":[{"name":"Department of Orofacial Pain Institute of Dental Surgery, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP)  Paris France"},{"name":"Laboratory of Orofacial Neurobiology, Inserm UMR 1333 Oral Health, Universit\u00e9 Paris Cit\u00e9  Montrouge France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102417738202"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102419893823"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102417694883"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001090"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/joor.12795"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/03331024211036152"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/joor.70020"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/joor.70051"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002243"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/joor.13123"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/joor.13945"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/25158163251339141"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/03331024261455835"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/03331024261452682"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102416646769"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/joor.13964"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/joor.13536"},{"key":"e_1_2_12_19_1","first-page":"927","volume-title":"Handbook of Clinical Neurology","author":"Reynolds E. 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