Neurophysin I: a reliable, novel, and robust biomarker for oxytocin.
Cihan Atila, Andi Nikaj, Svenja Leibnitz, Matthias E. Liechti, Mirjam Christ-Crain
European Journal of Endocrinology March 27, 2025 DOI: 10.1093/ejendo/lvaf078 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, placebo-controlled, crossover study Peer reviewed |
|---|---|
| Sample size | 30 |
| Population | Patients with hypothalamic-posterior-pituitary dysfunction and healthy controls matched by age, sex, body mass index, and menopause/hormonal contraceptive use |
| Intervention | MDMA |
| Dose | 100 mg |
| Duration | Single dose, measurements over 5 hours, with a 2-week wash-out period between sessions |
| Topics | MDMA |
| Keywords | Avp deficiency Biomarker Copeptin Diagnostic Hypopituitarism Oxytocin deficiency Posterior pituitary Vasopressin Neurophysin i markers Hormone measurement Drug stimulation tests Provocation testing |
| Citations | 9 |
| Key points | NP-I is validated as a biomarker for endogenous oxytocin secretion after MDMA stimulation, showing a significant difference in response between patients and healthy controls. |
Abstract
Oxytocin (OXT) deficiency is a recently identified novel psycho-neuroendocrine entity associated with anxiety and reduced prosocial behavior. 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. 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 (±3), sex, body mass index (±2), and menopause/hormonal contraceptives. Participants received a single oral dose of the strong OXT stimulator 3,4-methylenedioxymethamphetamine (MDMA, 100 mg) 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 = "not at all" to 100 = "extremely," or were bidirectionally ranging from -50 to +50 mm, with 0 being the neutral measure = "no effect." The primary endpoint-net incremental area under the curve (AUC) of NP-I from 0 to 300 min-was analyzed using a linear mixed-effects model. 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·5 h [1087-3696] and 97 pM·5 h [50-241] in healthy controls and patients, respectively, with a significant difference (2340 pM·5 h (95% CI, 1462-3218; P 0.5). 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.
Comparable studies
Other randomized controlled trials on MDMA, most cited first.
Citations in the library
Cited by 2
Cites 2
- Oxytocin and the Role of Fluid Restriction in MDMA-Induced Hyponatremia: A Secondary Analysis of 4 Randomized Clinical Trials. JAMA Network Open November 4, 2024
- Oxytocin in response to MDMA provocation test in patients with arginine vasopressin deficiency (central diabetes insipidus): a single-centre, case-control study with nested, randomised, double-blind, placebo-controlled crossover trial. The lancet. Diabetes & endocrinology July 2023