Neurophysin I: a reliable, novel, and robust biomarker for oxytocin.

Atila C, Nikaj A, Leibnitz S, Liechti ME, Christ-Crain M

European journal of endocrinology1 Mar 2025Cited by 8 (Europe PMC)

PMID40209095DOI10.1093/ejendo/lvaf078PepBankPUB-40209095

Publisher page PubMedAsk about this study

Summary

IntroductionOxytocin (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.Materials/methodsAnalysis 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.ResultsIn 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 < .0001). NP-I increase correlated with OXT increase (R = 0.92) and increases in subjective effects, eg, "good effect," "liking effect," "feeling high," "trust," and "fear reduction" (all R > 0.5).ConclusionThese 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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

No result from this study comes from a test of the peptide.

Natural levels measured7

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

01HumanEndogenous levelRandomized controlled trialOther
After MDMA, the neurophysin I area under the curve was higher in healthy controls than in patients with hypothalamic-posterior-pituitary dysfunction.
In plain wordsAfter MDMA, healthy people had a much larger rise in neurophysin I, a marker of the body's own oxytocin, than patients.
Peptide
Oxytocin
Outcome
IncreaseNP-I AUC after MDMA, healthy controls versus patients
Study
n = 30
Comparator
Patients
Analysis
Primary
Outcome group
Endogenous peptide levels · Endocrine and hormones
Measurements
NP-I AUC
2279 pM·5 h
healthy controls
NP-I AUC
97 pM·5 h
patients
AUC difference
2340 pM·5 h
controls vs patients
Source sentences
Summary
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 < .0001).
2 context sentences(design, population, supporting numbers)
Summary · context
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.
Summary · context
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.
This result measures the body's own Oxytocin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4020909505
02HumanEndogenous levelRandomized controlled trialOther
After MDMA, the increase in neurophysin I correlated strongly with the increase in oxytocin.
In plain wordsAfter MDMA, neurophysin I rose together with the body's own oxytocin, so it can serve as a marker.
Peptide
Oxytocin
Outcome
Not applicableCorrelation of NP-I increase with OXT increase
Study
n = 30
Outcome group
Endogenous peptide levels · Endocrine and hormones
Measurements
correlation R
0.92
NP-I vs OXT increase
Source sentences
Summary
NP-I increase correlated with OXT increase (R = 0.92) and increases in subjective effects, eg, "good effect," "liking effect," "feeling high," "trust," and "fear reduction" (all R > 0.5).
2 context sentences(design, population, supporting numbers)
Summary · context
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.
Summary · context
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.
This result measures the body's own Oxytocin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4020909506
03HumanEndogenous levelRandomized controlled trialOther
After MDMA, the increase in neurophysin I correlated with increases in subjective effects such as good effect, liking, feeling high, trust and fear reduction.
In plain wordsAfter MDMA, bigger rises in a marker of the body's own oxytocin were linked to stronger feelings such as liking, trust and feeling high.
Peptide
Oxytocin
Outcome
Not applicableCorrelation of NP-I increase with subjective drug effects
Study
n = 30
Outcome group
Endogenous peptide levels · Endocrine and hormones
Source sentences
Summary
NP-I increase correlated with OXT increase (R = 0.92) and increases in subjective effects, eg, "good effect," "liking effect," "feeling high," "trust," and "fear reduction" (all R > 0.5).
2 context sentences(design, population, supporting numbers)
Summary · context
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.
Summary · context
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.
This result measures the body's own Oxytocin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4020909507
04HumanEndogenous levelRandomized controlled trialOther
In healthy adults, MDMA induced an 8-fold increase in plasma oxytocin.
In plain wordsIn healthy adults, MDMA raised the body's own oxytocin about 8-fold.
Peptide
Oxytocin
Outcome
IncreasePlasma OXT after MDMA in healthy controls
Study
n = 15
Outcome group
Endogenous peptide levels · Endocrine and hormones
Measurements
OXT peak
624 pM
healthy controls after MDMA
OXT fold increase
8 fold
healthy controls after MDMA
Source sentences
Summary
In healthy controls, MDMA induced an 8-fold increase in OXT (peak: 624 pM [235-959])
2 context sentences(design, population, supporting numbers)
Summary · context
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.
Summary · context
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.
This result measures the body's own Oxytocin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4020909501
05HumanEndogenous levelRandomized controlled trialOther
In healthy adults, MDMA induced a 20-fold increase in neurophysin I, a co-released product of the oxytocin precursor.
In plain wordsIn healthy adults, MDMA raised neurophysin I, a marker released with the body's own oxytocin, about 20-fold.
Peptide
Oxytocin
Outcome
IncreasePlasma NP-I after MDMA in healthy controls
Study
n = 15
Outcome group
Endogenous peptide levels · Endocrine and hormones
Measurements
NP-I peak
1508 pM
healthy controls after MDMA
NP-I fold increase
20 fold
healthy controls after MDMA
Source sentences
Summary
and a 20-fold increase in NP-I (peak: 1508 pM [911-2233]).
2 context sentences(design, population, supporting numbers)
Summary · context
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.
Summary · context
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.
This result measures the body's own Oxytocin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4020909502
06HumanEndogenous levelRandomized controlled trialOther
In patients with hypothalamic-posterior-pituitary dysfunction, MDMA induced no notable increase in plasma oxytocin.
In plain wordsIn patients with hypothalamic-pituitary dysfunction, MDMA did not notably raise the body's own oxytocin.
Peptide
Oxytocin
Outcome
No significant changePlasma OXT after MDMA in patients
Study
n = 15
Outcome group
Endogenous peptide levels · Endocrine and hormones
Measurements
OXT peak
92 pM
patients after MDMA
Source sentences
Summary
In contrast, in patients, MDMA induced no notable increase in OXT (peak: 92 pM [79-110])
2 context sentences(design, population, supporting numbers)
Summary · context
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.
Summary · context
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.
This result measures the body's own Oxytocin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4020909503
07HumanEndogenous levelRandomized controlled trialOther
In patients with hypothalamic-posterior-pituitary dysfunction, MDMA induced only a mild increase in neurophysin I.
In plain wordsIn patients with hypothalamic-pituitary dysfunction, MDMA raised neurophysin I, a marker of the body's own oxytocin, only a little.
Peptide
Oxytocin
Outcome
IncreasePlasma NP-I after MDMA in patients
Study
n = 15
Outcome group
Endogenous peptide levels · Endocrine and hormones
Measurements
NP-I peak
263 pM
patients after MDMA
Source sentences
Summary
and only a mild increase in NP-I (peak: 263 pM [140-300]).
2 context sentences(design, population, supporting numbers)
Summary · context
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.
Summary · context
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.
This result measures the body's own Oxytocin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4020909504

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Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
11 Oct 2026, 00:50 UTC
Study results updated
Version 1
9 Oct 2026, 02:48 UTC
First added · source update from Europe PMC

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