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However, diagnosis and clinical progress have been hindered by challenges in reliably measuring OXT. Neurophysin I (NP-I), an equimolarly co-released cleavage product of the OXT precursor peptide, offers a promising alternative biomarker due to its stability, although it requires validation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Materials\/methods<\/jats:title>\n                  <jats:p>Analysis of a double-blind, placebo-controlled, cross-over study including 15 patients with hypothalamic-posterior-pituitary dysfunction and 15 healthy controls matched according to age (\u00b13), sex, body mass index (\u00b12), and menopause\/hormonal contraceptives. Participants received a single oral dose of the strong OXT stimulator 3,4-methylenedioxymethamphetamine (MDMA, 100\u2005mg) and placebo in random order, with a wash-out period of 2 weeks between both experimental sessions. NP-I and OXT levels were measured at 6 time points over 5 h after drug intake. Subjective drug effects were assessed using visual analog scales ranging from 0 = \u201cnot at all\u201d to 100 = \u201cextremely,\u201d or were bidirectionally ranging from \u221250 to +50 mm, with 0 being the neutral measure = \u201cno effect.\u201d The primary endpoint\u2014net incremental area under the curve (AUC) of NP-I from 0 to 300 min\u2014was analyzed using a linear mixed-effects model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In healthy controls, MDMA induced an 8-fold increase in OXT (peak: 624 pM [235-959]) and a 20-fold increase in NP-I (peak: 1508 pM [911-2233]). In contrast, in patients, MDMA induced no notable increase in OXT (peak: 92 pM [79-110]) and only a mild increase in NP-I (peak: 263 pM [140-300]). The AUC of NP-I after MDMA was 2279 pM\u00b75\u2005h [1087-3696] and 97 pM\u00b75\u2005h [50-241] in healthy controls and patients, respectively, with a significant difference (2340 pM\u00b75\u2005h (95% CI, 1462-3218; P &amp;lt; .0001). NP-I increase correlated with OXT increase (R = 0.92) and increases in subjective effects, eg, \u201cgood effect,\u201d \u201cliking effect,\u201d \u201cfeeling high,\u201d \u201ctrust,\u201d and \u201cfear reduction\u201d (all R &amp;gt; 0.5).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>These results validate NP-I as a biomarker for endogenous OXT secretion after stimulation with MDMA, addressing long-standing challenges in direct OXT measurement. NP-I offers novel opportunities for research in conditions where reduced OXT levels or disruptions in signaling are implicated, such as autism spectrum disorder, anxiety, and depression.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejendo\/lvaf078","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T19:40:51Z","timestamp":1744314051000},"page":"502-510","source":"Crossref","is-referenced-by-count":15,"title":["Neurophysin I: a reliable, novel, and robust biomarker for oxytocin"],"prefix":"10.1093","volume":"192","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5442-7304","authenticated-orcid":false,"given":"Cihan","family":"Atila","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel , 4031 Basel ,","place":["Switzerland"]},{"name":"Department of Clinical Research, University of Basel, University Hospital Basel , 4031 Basel 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