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

IF 5.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Cihan Atila, Andi Nikaj, Svenja Leibnitz, Matthias E Liechti, Mirjam Christ-Crain
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引用次数: 0

Abstract

Introduction: 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.

Materials/methods: 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.

Results: 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 < .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).

Conclusion: 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.

Neurophysin I:一种可靠、新颖、强大的催产素生物标志物。
引言:催产素(OXT)缺乏是最近发现的一种新的心理-神经内分泌实体,与焦虑和亲社会行为减少有关。然而,诊断和临床进展受到可靠测量OXT的挑战的阻碍。Neurophysin I (NP-I)是OXT前体肽的等量共释放裂解产物,由于其稳定性,它提供了一个有希望的替代生物标志物,尽管它需要验证。材料/方法:对一项双盲、安慰剂对照、交叉研究进行分析,该研究包括15名下丘脑-垂体后叶功能障碍患者和15名按年龄(±3)、性别、体重指数(±2)、更年期/激素避孕药匹配的健康对照组。参与者随机接受单次口服强OXT刺激剂3,4-亚甲基二氧基甲基苯丙胺(MDMA, 100毫克)和安慰剂,两次实验之间有2周的洗脱期。在给药后5h的6个时间点测量NP-I和OXT水平。使用视觉模拟量表评估主观药物效应,范围从0 =“完全没有”到100 =“非常”,或者双向范围从-50到+50毫米,其中0为中性测量=“无效果”。采用线性混合效应模型分析NP-I在0 ~ 300 min期间的主要终点曲线下净增量面积(AUC)。结果:在健康对照中,MDMA诱导OXT增加8倍(峰值:624 pM [235-959]), NP-I增加20倍(峰值:1508 pM[911-2233])。相比之下,在患者中,MDMA没有引起OXT的显著增加(峰值:92 pM[79-110]),只有轻微的NP-I增加(峰值:263 pM[140-300])。健康对照组和患者MDMA后NP-I AUC分别为2279 pM·5 h[1087-3696]和97 pM·5 h[50-241],差异有统计学意义(2340 pM·5 h (95% CI, 1462-3218;P < 0.0001)。NP-I的增加与OXT的增加相关(R = 0.92),与“好效果”、“喜欢效果”、“感觉高”、“信任”、“恐惧减少”等主观效果的增加相关(R均为0.5)。结论:这些结果验证了NP-I是MDMA刺激后内源性OXT分泌的生物标志物,解决了长期以来直接测量OXT的挑战。NP-I为涉及OXT水平降低或信号中断的情况(如自闭症谱系障碍、焦虑和抑郁)的研究提供了新的机会。
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来源期刊
European Journal of Endocrinology
European Journal of Endocrinology 医学-内分泌学与代谢
CiteScore
9.80
自引率
3.40%
发文量
354
审稿时长
1 months
期刊介绍: European Journal of Endocrinology is the official journal of the European Society of Endocrinology. Its predecessor journal is Acta Endocrinologica. The journal publishes high-quality original clinical and translational research papers and reviews in paediatric and adult endocrinology, as well as clinical practice guidelines, position statements and debates. Case reports will only be considered if they represent exceptional insights or advances in clinical endocrinology. Topics covered include, but are not limited to, Adrenal and Steroid, Bone and Mineral Metabolism, Hormones and Cancer, Pituitary and Hypothalamus, Thyroid and Reproduction. In the field of Diabetes, Obesity and Metabolism we welcome manuscripts addressing endocrine mechanisms of disease and its complications, management of obesity/diabetes in the context of other endocrine conditions, or aspects of complex disease management. Reports may encompass natural history studies, mechanistic studies, or clinical trials. Equal consideration is given to all manuscripts in English from any country.
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