SAT-044 Neurophysin I: A Reliable, Novel, and Robust Biomarker for OxytocinAn Analysis of a Double-Blind Placebo-Controlled Cross-Over Trial
Bibliographic record
Abstract
Abstract Disclosure: C. Atila: None. A. Nikaj: None. S. Leibnitz: None. M. Liechti: None. M. Christ-Crain: None. Background: Oxytocin (OXT) deficiency is a recently identified new neuroendocrine entity associated with anxiety and reduced prosocial behavior. However, diagnosis and clinical progress have been hindered by challenges in reliably measuring OXT due to its instability and short half-life. Neurophysin I (NP-I), an equimolarly co-released cleavage product of the OXT precursor peptide, offers a promising alternative biomarker due to its stability and longer half-life, though it requires validation. Methods: Analysis of a double-blind, placebo-controlled, cross-over study including 15 patients with hypothalamic-posterior-pituitary dysfunction and 15 matched healthy controls (according to age (+/-3), sex, body mass index [BMI] (+/-2), and menopause/hormonal contraceptives). Participants received a single oral of the strong OXT stimulator 3,4-methylenedioxymethamphetamine (MDMA, 100mg) and placebo, separated by two weeks. NP-I and OXT levels were measured at six time points over five hours. Subjective drug effects were assessed using visual analog scales. The area under the curve (AUC) in plasma NP-I from 0 to 300 minutes between both groups was analyzed using linear mixed-effects regression model. The AUC in receiver-operating characteristics curve (ROC) was assessed for MDMA-stimulated NP-I and OXT in differentiating patients from healthy controls. Results: The median age was 34 years [IQR 25-46] in patients and 35 years [IQR 26-48] in controls, with both groups consisting of 53% (n=8) females.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, 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·5h [1087-3696] in healthy controls and 97 pM·5h [50-241] in patients, with a significant difference of 2340 pM·5h (95%-CI [1462-3218]; p<0.0001). NP-I strongly correlated with OXT (R=0.92) and increases in subjective effects, e.g., ‘liking effect,’ ‘feeling high,’ ‘trust,’ and ‘fear reduction’ (all R>0.5). MDMA-stimulated NP-1 demonstrated strong diagnostic performance in differentiating patients with OXT deficiency from healthy controls with a ROC-AUC of 100%. Conclusion: These results validate NP-I as a novel biomarker for endogenous OXT secretion, 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. Presentation: Saturday, July 12, 2025
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.007 | 0.004 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".