Oxytocin, vasopressin, and cortisol are widely used as biomarkers to assess the temperament or emotional state of dogs. Typically, these levels are measured in blood; however, this invasive procedure can induce acute pain and stress. Considering the welfare of dogs, it is necessary to replace these procedures with noninvasive methods. Saliva sampling has emerged as a promising, noninvasive alternative for measuring hormonal levels. Nonetheless, it remains unclear whether saliva samples accurately reflect plasma hormonal levels in dogs. The objective of this study was to evaluate the correlations of oxytocin, vasopressin, and cortisol levels between plasma and saliva samples. We simultaneously collected blood and saliva samples from fifteen beagles, aged six, including eleven females and four sterilized males. Due to the limited availability of saliva samples, each analysis was performed on 5-11 dogs. Hormonal levels were quantified using commercial ELISA kits. Linear regression analysis and Pearson's correlation coefficient were used for statistical analysis. Our findings revealed no significant correlation between oxytocin or vasopressin levels in the plasma and salivary samples. However, a significant positive correlation was observed between cortisol levels in plasma and saliva samples. Additionally, oxytocin and vasopressin levels were positively correlated in both plasma and saliva samples. A positive correlation was found between the plasma cortisol and oxytocin levels, whereas no correlation was observed between the salivary cortisol and oxytocin levels. This study provides a foundation for understanding hormonal relationships across different matrices, contributing to the development of alternative sampling methods that prioritize animal welfare.

Complex mechanisms govern the transport and action of oxytocin (Oxt), a neuropeptide and hormone that mediates diverse physiologic processes. While Oxt exerts site-specific and rapid effects in the brain via axonal and somatodendritic release, volume transmission via CSF and the neurovascular interface can act as an additional mechanism to distribute Oxt signals across distant brain regions on a slower timescale. This review focuses on modes of Oxt transport and action in the CNS, with particular emphasis on the roles of perivascular spaces, the blood-brain barrier (BBB), and circumventricular organs in coordinating the triadic interaction among circulating blood, CSF, and parenchyma. Perivascular spaces, critical conduits for CSF flow, play a pivotal role in Oxt diffusion and distribution within the CNS and reciprocally undergo Oxt-mediated structural and functional reconstruction. While the BBB modulates the movement of Oxt between systemic and cerebral circulation in a majority of brain regions, circumventricular organs without a functional BBB can allow for diffusion, monitoring, and feedback regulation of bloodborne peripheral signals such as Oxt. Recognition of these additional transport mechanisms provides enhanced insight into the systemic propagation and regulation of Oxt activity.

The development of oxytocin as a therapeutic agent outside of obstetrics has been hampered by antibody-based assays that lack specificity, leading to inconsistent and incompletely reported pharmacokinetic models to guide drug dosing. This study describes the population plasma pharmacokinetics of intravenous and intranasal oxytocin using a sensitive and specific liquid chromatography-tandem mass spectroscopy (LC/MS) assay.

Two studies in healthy adult men and nonpregnant women were performed, the first with intravenous oxytocin 16.7 μg over 1 or 10 min and the second with intravenous oxytocin 13.7 μg over 30 min and, on a separate day, intranasal oxytocin 100 μg (n=24). Venous plasma oxytocin concentration was measured using LC/MS and enzyme-linked immunosorbent assay. Pharmacokinetic parameters were estimated using NONMEM.

The pharmacokinetics of intravenous oxytocin were well described by a two-compartment model (0% bias, 18% median inaccuracy). The two-compartment model for intranasal oxytocin was characterised by substantial subject-to-subject variability (9% median bias, 47% median inaccuracy). Nasal oxytocin bioavailability was 0.7%. Oxytocin samples assayed with LC/MS were systematically higher than simultaneous samples assayed with enzyme-linked immunosorbent assay.

The pharmacokinetics of intravenous oxytocin are well described by a two-compartment model. The low bioavailability (<1%) and large intersubject variability in plasma oxytocin after intranasal dosing could partially explain the inconsistent reports of oxytocin efficacy in the clinical literature with this delivery method. A publicly available simulator was created to guide oxytocin dosing in future studies.

NCT03929367 (Study 1) and NCT05672667 (Study 2).

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 < .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).

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.

This study examines how different concentrations of arginine vasopressin (AVP) and its preservative chlorobutanol (ClB) impact the immune functions of human polymorphonuclear neutrophils (PMNs), which are crucial in the immune response, particularly in sepsis. Using a model to simulate the physiological, sepsis-related, and therapeutic AVP levels in plasma, we analysed how AVP and ClB affect PMN activities, including reactive oxygen species (ROS) production, NETosis, antigen expression, and migration. PMNs were isolated from whole human blood and assessed using flow cytometry and live cell imaging. The results indicated that neither AVP nor ClB significantly affected PMN viability, antigen expression, NETosis, or ROS production in response to N-Formylmethionine-leucyl-phenylalanine, or fMLP, and tumour necrosis factor alpha. In the migration assays, concentration-dependent effects were observed. At physiological AVP levels, PMN migration showed no reduction, while the sepsis-associated AVP levels initially reduced migration before returning to the baseline or even increasing. The therapeutic AVP concentrations showed similar migration to that in the controls, while high concentrations progressively inhibited migration. ClB, regardless of its concentration, enhanced PMN migration. These findings suggest that AVP during sepsis may impair PMN migration, potentially contributing to tissue damage and systemic complications. This highlights AVP's role as a possible immune modulator in complex immune responses.

Two lines of research, on outcome moderators and on novel treatment targets, seek to improve the overall efficacy of child anxiety treatment, with mixed results. We propose that an integration of both lines of research can lead to improved treatment efficacy. In a first proof of concept of this approach, we studied whether the interaction between baseline levels and targeted changes in peripheral oxytocin (OT) can predict differential responses to two childhood anxiety treatments.

A total of 124 mother-child dyads participated in the study. Children's salivary OT levels were measured at baseline and again, immediately after an experimental dyadic interaction in the lab. Dyads were subsequently randomized to receive one of two treatments, differing in their targets: SPACE (Supportive Parenting for Anxious Childhood Emotions) and CBT (cognitive-behavioral therapy). Treatment outcomes were assessed using the Childhood Anxiety Related Emotional Disorders scale, reported by both mother and child.

The findings suggest that in SPACE, where the mother is the main agent of change, higher baseline levels of child OT, coupled with increases in OT following a positive mother-child interaction, predicted greater treatment efficacy. By contrast, in CBT, where the child is the main agent of change, higher baseline levels of child OT, coupled with a decrease in OT following the interaction, predicted greater treatment efficacy.

The findings highlight the importance of the integration between moderators and targets of treatments for progress toward improving treatment efficacy through precision medicine.

Music therapy has been in practice for years. However, the mechanism of action of music or music therapy is not well understood. It is only recently that the neuroendocrinological basis of therapeutic relationships has become the subject of growing research interest. The aim of this pilot study (Clinical Trial No: DRKS00035174) is to investigate whether oxytocin is usable and feasible as a biomarker of attachment to demonstrate the development of therapeutic alliance between therapist and patient in a dyadic music therapy setting.

In a single-measure crossover design, children aged 6-12 years from a special school for social and emotional disorders, were randomly with either music therapy followed by a waiting list control group that performed silent work, or vice versa. The respective interventions were conducted on the school premises on different days over a period of 1 month. The primary outcome was salivary oxytocin, with tests performed immediately before and after each 30-min intervention.

Thirty-two children were included in the study, resulting in n = 16 children per allocation sequence. During the implementation of the study, difficulties were encountered with protocol adherence both in terms of the duration of the music therapy and the implementation of the silent work in the control group. There were no dropouts, however, only 28 children were included in the final data analysis as two participants in each group were excluded due to large fluctuations in oxytocin levels. Between-group comparison and within-group comparisons showed no significant changes in oxytocin levels. However, the music therapist showed a significant increase in oxytocin levels in the before after measurement. No side effects or adverse events were reported during the trial.

The findings indicated a responsiveness of oxytocin to musical stimulation. Although feasibility of oxytocin measurement was clearly demonstrated, evaluation of the results is difficult against the background of many remaining questions regarding individual and contextual factors influencing the oxytocinergic system. Moreover, the clinical significance of changes in oxytocin levels remains a topic for further research to better understand the role of oxytocin in the attachment formation between therapist and patient in music therapy.

Increasing evidence supports the presence of oxytocin deficiency (OXT-D) in patients with hypopituitarism and hypothalamic damage (HHD), that might be associated with neuropsychological deficits and sexual dysfunction, leading to worse quality of life (QoL). Therefore, identifying a provocative test to diagnose an OXT-D will be important. Corticotropin-releasing hormone (CRH) is a candidate for such a test as it increases oxytocin secretion in animal models. This study aimed to examine the effects of CRH on oxytocin release in HHD compared to healthy controls (HC) and to describe the psychopathology, sexual function and QoL and their associations with oxytocin. This is a single-blind, randomized, placebo-controlled, proof-of-concept study (NCT04902235) with crossover assignment (CRH vs. placebo). Nineteen HHD patients (10 females) and 20 HC (11 females) completed two visits, receiving CRH or placebo in random order and completed validated questionnaires to assess psychopathology, sexual function and QoL. Samples were collected over 120 min to assess oxytocin. Linear mixed-effects regression model evaluated the change in oxytocin after CRH/placebo in HHD vs. HC. CRH administration did not impact oxytocin concentrations across groups over time (p = 0.97). HHD had greater psychopathology (most ps < 0.05), sexual dysfunction (p < 0.03) and worse QoL (p < 0.001) compared to HC, nevertheless, baseline oxytocin concentrations and area under the curve of oxytocin were not significantly associated with psychopathology, sexual function or QoL, neither in HHD or HC. In conclusion, CRH administration does not appear to be a suitable provocative test for diagnosing OXT-D in HHD. Identifying a reliable diagnostic test for OXT-D remains crucial. Alternative provocative tests or biomarkers should be explored.

Craniopharyngioma is a benign tumour affecting the hypothalamic and pituitary regions, which are involved in the production and secretion of oxytocin. We conducted a systematic review to assess dysregulation of the oxytocin system in craniopharyngioma and associations with neurobehavioural, eating, and metabolic abnormalities. Eight studies (n = 72 patients) were included. Evidence for dysfunction of the endogenous oxytocin system in craniopharyngioma is limited and mixed. While no significant differences in baseline salivary oxytocin concentrations were reported between patients with craniopharyngioma and controls, patients with craniopharyngioma were found to have blunted salivary oxytocin response following exercise stimulation and this was associated with greater state anxiety and higher BMI. Studies administering exogenous oxytocin are sparse and do not meet required standards. Hypothalamic damage may pose an additional mechanism of oxytocin dysregulation. Improving understanding of the oxytocin system in craniopharyngioma could be pivotal for exploring the potential therapeutic role of exogenous oxytocin in this condition.

Individuals diagnosed with functional neurological disorder experience abnormal movement, gait, sensory processing or functional seizures, for which research into the pathophysiology identified psychosocial contributing factors as well as promising biomarkers. Recent pilot studies suggested that (epi-)genetic variants may act as vulnerability factors, for example, on the oxytocin pathway. This study set out to explore endogenous oxytocin hormone levels in saliva in a cohort of 59 functional neurological disorder patients and 65 healthy controls comparable in sex and age. First, we examined the association between salivary oxytocin levels with the genetic allelic variant (rs53576) of the oxytocin receptor gene (OXTR), its epigenetic changes indicated by methylation rates, and clinical variables-including childhood trauma. Second, due to previously reported effects of oxytocin changing the volume and functional connectivity of the amygdala, as well as the known involvement of the amygdala in the pathophysiology of functional neurological disorders, we further looked at both structural and functional imaging of the amygdala. While patients did not significantly differ from healthy control in their peripheral oxytocin levels, there was a specific interaction of OXTR methylation and peripheral oxytocin dependent on group: higher methylation rates correlated with higher salivary oxytocin in patients only, while this was not the case in healthy control [F(1109) = 8.92, P = 0.003, d = 0.541]. Moreover, patients with the AA-genotype (minor allele) of the rs53576 genetic variant of the OXTR gene presented with higher OXTR methylation levels [F(2106) = 10.25, P < 0.0001, d = 0.58]. Lastly, amygdalar connectivity to the hippocampus, the posterior cingulate cortex, the inferior parietal cortex and the inferior temporal cortex as well as smaller amygdalar volume were correlated to peripheral oxytocin levels in patients only [F(2,38) = 5.36, P  = 0.025,  d = 0.431], but not in healthy control. No significant interactions with childhood trauma were identified. Our study revealed a significant interplay between peripheral oxytocin and OXTR methylation in patients only, potentially influenced by genotype. One could hypothesize that higher peripheral oxytocin denotes a compensatory mechanisms for the increased methylation of the OXTR, which might affect amygdalar functional connectivity. These findings help to further understand underlying pathophysiological mechanisms, considering oxytocin's involvement in functional patients and could offer a potential site of treatment for future studies.

The development of fetal organs can be impacted by systemic changes in maternal circulation, with the placenta playing a pivotal role in maintaining pregnancy homeostasis and nutrient exchange. In clinical obstetrics, oxytocin (OXT) is commonly used to induce labor. To explore the potential role of OXT in the placental homeostasis of OXT, we compared OXT levels in neonatal cord blood among neonates (23-42 weeks gestation) whose mothers either received prenatal OXT or experienced spontaneous labor. Our previous research revealed that the oxytocin receptor (OXTR), essential in forming the blood-retina barrier, is expressed in the retinal pigment epithelium (RPE). We hypothesized that perinatal OXT administration might influence the development of the neural retina and its vasculature, offering therapeutic potential for retinal diseases such as retinopathy of prematurity (ROP). Plasma OXT levels were measured using a commercial OXT ELISA kit. Human fetal RPE (hfRPE) cells treated with OXT (10 µM) were assessed for gene expression via RNA sequencing, revealing 14 downregulated and 32 upregulated genes. To validate these differentially expressed genes (DEGs), hfRPE cells were exposed to OXT (0.01, 0.1, 1, or 10 µM) for 12 h, followed by RNA analysis via real-time PCR. Functional, enrichment, and network analyses (Gene Ontology term, FunRich, Cytoscape) were performed to predict the affected pathways. This translational study suggests that OXT likely crosses the placenta, altering fetal OXT concentrations. RNA sequencing identified 46 DEGs involved in vital metabolic and signaling pathways and critical cellular components. Our results indicate that the perinatal administration of OXT may affect neural retina and retinal vessel development, making OXT a potential therapeutic option for developmental eye diseases, including ROP.

Oxytocin has various effects ranging from promoting labor in pregnant women to alleviating stress. Recently, we reported the hair growth-promoting effects of oxytocin in hair follicle organoids. However, its clinical application faces challenges such as rapid degradation in vivo and poor permeability due to its large molecular weight. Therefore, in this study, we investigated the effects of the oxytocin receptor (OXTR) agonists WAY267464 and LIT001 as alternatives to oxytocin on hair growth. Human dermal papilla (DP) cells were cultured in WAY267464 or LIT001-supplemented medium. The addition of WAY267464 and LIT001 increased the expression of hair growth-related genes in DP cells. We tested the hair growth-promoting effects of WAY267464 and LIT001 using hair follicle organoids in vitro and found that they significantly promoted hair follicle sprouting. Thus, our findings indicate that WAY267464 and LIT001 are potential hair growth agents and may encourage further research on the development of novel hair growth agents targeting OXTR in patients with alopecia.

Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. To prevent PPH, the WHO recommends administration of oxytocin (OT) immediately after birth, i.e. during the third stage of labour (TSL). Previous studies demonstrate that methods to quantify OT in biological matrices, e.g. enzyme-linked immunosorbent assays (ELISA), radioimmunoassays (RIA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) lack the specificity and/or sensitivity to accurately quantify OT in plasma from women administered OT during TSL. This is due to increased metabolic clearance of OT in late-stage pregnancy and at the time of childbirth, resulting in extremely low OT plasma concentrations. This study describes the development of an ultra-sensitive bioanalytical method that overcomes the issues previously reported and enables accurate pharmacokinetic analyses of exogenously administered OT in TSL.

A selective and sensitive assay to quantify OT in TSL plasma was developed. Immunoprecipitation (IP) was applied to selectively extract OT from the TSL plasma, thereby generating clean extracts compatible with nanoflow LC (nLC). nLC-MS/MS was chosen for its high sensitivity and ability to differentiate between OT and potentially co-captured OT-like immunoreactive products.

The presented methodology is accurate and precise, with a good linear fit between 100-10 000 fg mL-1 OT. TSL plasma samples from a clinical phase 1 study (NCT02999100) were analysed successfully, enabling OT quantification down to 100 fg mL-1.

The presented IP-nLC-MS/MS method succeeded in overcoming the sensitivity challenge related to the assay of OT in TSL plasma and thereby revealing the PK profiles of OT in TSL plasma clinical study samples.

This paper presents an aptameric graphene nanosensor for rapid and sensitive measurement of arginine vasopressin (AVP) toward continuous monitoring of critical care patients. The nanosensor is a field-effect transistor (FET) with monolayer graphene as the conducting channel and is functionalized with a new custom-designed aptamer for specific AVP recognition. Binding between the aptamer and AVP induces a change in the carrier density in the graphene and resulting in measurable changes in FET characteristics for determination of the AVP concentration. The aptamer, based on the natural enantiomer D-deoxyribose, possess optimized kinetic binding properties and is attached at an internal position to the graphene for enhanced sensitivity to low concentrations of AVP. Experimental results show that this aptameric graphene nanosensor is highly sensitive (with a limit of detection of 0.3 pM and a resolution of 0.1 pM) to AVP, and rapidly responsive (within 90 s) to both increasing and decreasing AVP concentration changes. The device is also reversable (within 4%), repeatable (within 4%) and reproducible (within 5%) in AVP measurements.

Oxytocin and cortisol are hormones that can influence cognition and behavior, but the relationships between endogenous concentrations and individual differences in cognitive and behavioral phenotypes remain poorly understood. Across mammals, oxytocin has important roles in diverse social behaviors, and in dogs, it has been implicated in human-oriented behaviors such as social gaze and point-following. Cortisol, an end-product of the hypothalamic-pituitary-adrenal (HPA) axis, is often studied in relation to temperament and emotional reactivity, but it is also known to modulate executive functions. In this study, we measured basal fecal cortisol (n = 247) and plasma oxytocin (n = 249) in dog puppies from a pedigreed population (Canine Companions ®). We collected cognitive and behavioral data from these subjects (n = 247), including measures of human-oriented social cognition, memory, inhibitory control, perceptual discriminations, and temperament. Oxytocin concentrations were estimated to be very highly heritable (h2 = 0.90-0.99) and cortisol concentrations were estimated to be moderately-highly heritable (h2 = 0.43-0.47). Bayesian mixed models controlling for relatedness revealed that oxytocin concentrations were positively associated with spatial working memory and displayed a negative quadratic relationship with behavioral laterality, but no credible associations were seen for social measures. Cortisol concentrations exhibited a negative linear relationship with performance on an inhibitory control task and a negative quadratic relationship with bold behavioral reactions to a novel object. Collectively, our results suggest that individual differences in oxytocin and cortisol concentrations are under strong genetic control in dogs and are associated with phenotypic variation in aspects of temperament, behavioral laterality, and executive function.

Hormones are specific molecules measured in biological fluids by elaborate analytical systems requiring meticulous attention. Variation between laboratories can be expected. However, recently published measurements of AVP, OXT, and BNP in human plasma under basal/control conditions include numbers which, between publications, vary by 100-10 000-fold. Generally, the methods descriptions are scant, at best, and provide no information about quality control measures. Clearly, two results describing the same basal hormone concentration by numbers three orders of magnitude apart are incongruent providing reason for concern. Basal concentrations of bioactive AVP, OXT, and BNP in human plasma are in the order of 1-10 pmol/L. Therefore, assay systems applied to plasma must be able to measure concentrations of less than 1 pmol/L with appropriate specificity and accuracy. Basal concentrations of AVP, OXT, and BNP above 100 pmol/L should be reconsidered, as such results do not reflect bioactive hormone levels in humans, rats, or mice. Any concentration above 1000 pmol/L is of concern because such levels of bioactive hormone may be seen only under extreme conditions, if at all.

Polyuria-polydipsia syndrome can be caused by central diabetes insipidus, nephrogenic diabetes insipidus or primary polydipsia. To avoid confusion with diabetes mellitus, the name 'central diabetes insipidus' was changed in 2022 to arginine vasopressin (AVP) deficiency and 'nephrogenic diabetes insipidus' was renamed as AVP resistance. To differentiate the three entities, various osmotic and non-osmotic copeptin-based stimulation tests have been introduced in the past decade. The hypertonic saline test plus plasma copeptin measurement emerged as the test with highest diagnostic accuracy, replacing the water deprivation test as the gold standard in differential diagnosis of the polyuria-polydipsia syndrome. The mainstay of treatment for AVP deficiency is AVP replacement with desmopressin, a synthetic analogue of AVP specific for AVP receptor 2 (AVPR2), which usually leads to rapid improvements in polyuria and polydipsia. The main adverse effect of desmopressin is dilutional hyponatraemia, which can be reduced by regularly performing the so-called desmopressin escape method. Evidence from the past few years suggests an additional oxytocin deficiency in patients with AVP deficiency. This potential deficiency should be further evaluated in future studies, including feasible provocation tests for clinical practice and interventional trials with oxytocin substitution.

Oxytocin (OXT), a neuropeptide consisting of only nine amino acids, is synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. Although OXT is best known for its role in lactation and parturition, recent research has shown that it also has a significant impact on social behaviors in mammals. However, a comprehensive review of this topic is still lacking. In this paper, we systematically reviewed the effects of OXT on social behavior in mammals. These effects of OXT from the perspective of five key behavioral dimensions were summarized: parental behavior, anxiety, aggression, attachment, and empathy. To date, researchers have agreed that OXT plays a positive regulatory role in a wide range of social behaviors, but there have been controversially reported results. In this review, we have provided a detailed panorama of the role of OXT in social behavior and, for the first time, delved into the underlying regulatory mechanisms, which may help better understand the multifaceted role of OXT. Levels of OXT in previous human studies were also summarized to provide insights for diagnosis of mental disorders.

Oxytocin (OT) is a peptide hormone synthesized in the hypothalamus and released into systemic circulation or other areas of the brain. Its physiological roles include action as a hormone with stimulation of uterine contractions and that as a neuromodulator with involvement in social behaviors and regulation of mood. Its small size and low levels within biological matrices make it challenging to accurately measure. The goal of this study was to demonstrate the specificity of the antibody, sensitivity, and reproducibility of the Phoenix Pharmaceuticals (PP) OT radioimmunoassay (RIA) for use in human urine, serum, and saliva. Specificity of the antibody was assessed by high pressure liquid chromatography with ultraviolet (HPLC-UV) separation and assay of the fractions. Immunoreactivity was evaluated using the percent OT bound, and the fraction retention times were compared to the retention time of an intact OT standard to determine which fractions contained OT in the extracted samples. Reproducibility was assessed by running replicates of pools of each biomatrix over several assays. Sensitivity was assessed by repeated measurement of physiologically relevant low-concentration specimens. In all tested specimens the greatest reactivity in assay corresponded to the same fraction(s) as the OT standard. Only minimal reactivity was found in the other fractions, suggesting that in an unfractionated sample the antibody reacts mostly with intact OT. Reproducibility was acceptable for all specimens and the coefficient of variation (CV) ranged from 3.72 to 8.04% and 5.89-12.8%, for intra and inter-assay, respectively. The limits of quantitation (LOQ) were sufficient for measurement of normal values in urine (0.643 & 1.43 pg/mL), serum (1.90 pg/mL), and saliva pools (0.485 & 4.42 pg/mL). In conclusion, the PP OT RIA is specific and sensitive enough for reproducible measurement of intact OT in human peripheral biological matrices.

Given its putative roles in mediating prosocial behavior, attachment bonds, and stress physiology, oxytocin modulation has been hypothesized to be a biological correlate of the salubrious effects of meditation practice. Here we investigated the effects of a month-long silent meditation retreat on changes in oxytocin, and the related hormone and vasopressin, in relation to psychosocial changes in attachment style, anxiety, personality measures, and feelings of social connectedness with fellow meditators.

Plasma oxytocin and vasopressin and self-report questionnaires were measured in retreat participants (n = 28) at the beginning of, and 3 weeks into, a residential meditation retreat. Control participants (n = 34), who were similar in age, gender, and meditation experience, were also assessed across a 3-week interval. Linear mixed effects models were used to assess outcomes.

The retreat group showed a small but significant decrease in oxytocin compared to controls who showed no change. In the retreat group, higher openness to experience at Time 1 predicted greater reductions in oxytocin during the retreat, and lower oxytocin at Time 2 was related to stronger feelings of personal connection with fellow meditators. The changes in oxytocin were not related to attachment style or anxiety. Vasopressin decreased over time across both groups, suggesting no specific effect of retreat.

These preliminary findings suggest that meditation training in the context of a silent residential retreat may reduce circulating levels of oxytocin. We interpret this finding from multiple theoretical perspectives, discussing key measurement limitations and proposing future study designs that may help to differentiate the effects of different meditation practices and contexts on oxytocin signaling.

Equine-assisted services (EAS) has received attention as a potential treatment strategy for post-traumatic stress disorder (PTSD), as existing literature indicates that symptoms may decrease following EAS. Relatively little is known about the mechanisms at play during lessons and if physiological measures are impacted. The objectives of this pilot study were to 1) explore the effects of adaptive horsemanship (AH) lessons on symptoms of PTSD, hormone concentrations, and social motor synchrony; 2) determine if physiological changes occur as veterans interact with horses; and 3) explore if the interaction between veteran and horse changes over the 8-week session.

Veterans with PTSD were randomly assigned to control (CON, n = 3) or AH (n = 6) groups for an 8-week period (clinical trial; NCT04850573; clinicaltrials.gov). Veterans completed the PTSD Checklist (PCL-5) and Brief Symptom Inventory (BSI) at pre-, post-, and 2- and 6-month follow-up time points. They also completed a social motor synchrony test (pendulum swinging) and blood draw at pre- and post-time points. In weeks 1, 4, and 8, blood samples were drawn at 0 min, 3 min, 5 min, 25 min, and 30 min during the 30-min AH lessons. Veterans completed the Human-Animal Interaction Scale (HAIS) after each lesson. Blood samples were assayed for plasma cortisol, epinephrine, norepinephrine, and oxytocin. Data were analyzed with repeated measure ANOVAs. Changes in PTSD symptoms from pre- to post-time point were analyzed with paired t-tests.

Changes in PCL-5 scores tended to differ (p = 0.0989), and global BSI scores differed (p = 0.0266) between AH (-11.5 ± 5.5, mean ± SE; -0.5 ± 0.2) and CON (5.3 ± 5.4; 0.4 ± 0.2) groups. Social motor synchrony and hormone concentrations did not differ between groups or time points (p > 0.05). Cortisol, norepinephrine, and oxytocin concentrations did not differ across sessions (p > 0.05). Epinephrine concentrations tended (p = 0.0744) to decrease from week 1 to 4 of sessions. HAIS scores increased (p ≥ 0.0437) in week 3 and remained elevated as compared to week 1.

Participant recruitment was the greatest challenge. These preliminary results agree with the literature suggesting that EAS can reduce symptoms of PTSD.

Little literature exists on horses in adaptive horsemanship (AH) despite concerns about their well-being. The study objective was to evaluate behavioral and physiological responses of horses to ground-based AH lessons for veterans with post-traumatic stress disorder (PTSD). Lessons were expected to alter horses' hormone concentrations, behavior, and muscle activity. Geldings were assigned to AH (n=6; 20.3 ± 1.9 yrs., mean ± SE) or control (CON; stall in arena, n=6; 13.8 ± 1.7 yrs.) conditions for 8-week sessions based on current occupation (AH = equine-assisted services; CON = recreational riding). Plasma cortisol, epinephrine, norepinephrine, and oxytocin concentrations from samples at 0 (start of lesson), 3, 5, 25, and 30 (end) min were determined using assays validated in horses. Surface electromyography (sEMG) (masseter and brachiocephalic; Noraxon, Scottsdale, AZ, USA) and video were recorded continuously. Average rectified values (ARV) and median frequency (MF) were calculated (100 ms) after sEMG data were normalized, rectified, and filtered. The number, number of unique, and duration of stress related behaviors (ethogram) were recorded by three trained (ĸ ≥ 0.7) observers. Data were analyzed with repeated measures ANOVAs (significance P ≤ 0.05) with fixed effects of treatment, time point, week, and their interactions as appropriate and random effect of horse. CON horses had elevated cortisol concentrations (P = 0.0023) at 25 and 30 min. AH horses displayed fewer (P ≤ 0.0491) stress related and unique behaviors. CON horses were described as more (P < 0.0001) anxious, nervous, and stressed than AH horses (calm, comfortable, patient, and relaxed) in qualitative behavior analysis (22 observers). AH horses were less stressed than CON horses.

Although best known for its established role in mediating parturition and lactation, the highly-conserved neuropeptide hormone oxytocin also mediates a range of social and stress-buffering processes across mammalian species. Measurements of peripheral oxytocin in plasma have long been considered the gold standard, but there is increasing interest in developing methods to detect oxytocin non-invasively in saliva. Here we present an analytical and biological validation of a novel method to measure salivary oxytocin (sOXT) in an under-studied research group: farm animals. Given their similarities with humans in physiology and brain, methods that can identify valued social contexts and social relationships for farm animals and investigate their function have implications for clinical research as well as for animal welfare science. However, current methods to measure sOXT vary greatly in terms of sample collection, pre-measurement processing and measurement and more rigorous standardization and validation of methods is critical to determine the utility of sOXT as a biomarker of salient social events and related emotions. We optimized a method for extracting sOXT in pigs and horses and measured sOXT in extracted samples using a commercially available enzyme-immunoassay. Extracted samples were within acceptable ranges for precision (CVs < 15.2%), parallelism and recovery (94%-99%) in both species. Salivary oxytocin increased in samples collected during birth in pigs (Friedmans, p = 0.02) and horses (Wilcoxon, p = 0.02). Salivary oxytocin tended to decrease in sows after a 90-min separation from their piglets (Wilcoxon, p = 0.08). We conclude that sOXT can be reliably linked to physiological events that are mediated by the oxytocinergic system in farm animals, but that more research is needed to determine whether sOXT is a reliable trait marker for more general oxytocin system activation in response to salient social events. Future research should characterize how individual attributes and salivary parameters influence sOXT measurement and should emphasize reporting of analytical and biological validations to increase acceptance of non-invasive methods.

Oxytocin is a pleiotropic neuropeptide that plays roles in biological processes ranging from birth, lactation, and social bonding to immune function, cardiovascular repair, and regulation of appetite. Although measurements of endogenous oxytocin concentrations have been performed for more than 50 years, the ability to measure oxytocin accurately poses notable challenges. One potential solution for overcoming these challenges involves measurement of oxytocin's carrier molecule - neurophysin I (NP-1) - as a surrogate biomarker. NP-1 is secreted in equimolar concentrations with oxytocin but has a longer half-life, circulates in higher concentrations, and can be measured using a sandwich immunoassay. We report experiments that 1) analytically validate a commercially available NP-1 sandwich immunoassay for use with human plasma and urine samples, 2) confirm the specificity of this assay, based on detection of NP-1 in plasma from wild-type but not oxytocin knockout mice, 3) demonstrate that NP-1 concentrations are markedly elevated in late pregnancy, consistent with studies showing substantial increases in plasma oxytocin throughout gestation, and 4) establish strong correlation between NP-1 and plasma oxytocin concentrations when oxytocin is measured in extracted (but not non-extracted) plasma. The NP-1 assay used in this study has strong analytical properties, does not require time-intensive extraction protocols, and the assay itself can be completed in < 2 h (compared to 16-24 h for a competitive oxytocin immunoassay). Our findings suggest that much like copeptin has become a useful surrogate biomarker in studies of vasopressin, measurements of NP-1 have similar potential to advance oxytocin research.

Oxytocin is a reproductive hormone implicated in the process of parturition and widely used during labor. Oxytocin is produced within the supraoptic nucleus and paraventricular nucleus of the hypothalamus and released from the posterior pituitary lobe into the circulation. Oxytocin is released in pulses with increasing frequency and amplitude in the first and second stages of labor, with a few pulses released in the third stage of labor. During labor, the fetus exerts pressure on the cervix of the uterus, which activates a feedforward reflex-the Ferguson reflex-which releases oxytocin. When myometrial contractions activate sympathetic nerves, it decreases oxytocin release. When oxytocin binds to specific myometrial oxytocin receptors, it induces myometrial contractions. High levels of circulating estrogen at term make the receptors more sensitive. In addition, oxytocin stimulates prostaglandin synthesis and release in the decidua and chorioamniotic membranes by activating a specific type of oxytocin receptor. Prostaglandins contribute to cervical ripening and uterine contractility in labor. The oxytocin system in the brain has been implicated in decreasing maternal levels of fear, pain, and stress, and oxytocin release and function during labor are stimulated by a social support. Moreover, studies suggest, but have not yet proven, that labor may be associated with long-term, behavioral and physiological adaptations in the mother and infant, possibly involving epigenetic modulation of oxytocin production and release and the oxytocin receptor. In addition, infusions of synthetic oxytocin are used to induce and augment labor. Oxytocin may be administered according to different dose regimens at increasing rates from 1 to 3 mIU/min to a maximal rate of 36 mIU/min at 15- to 40-minute intervals. The total amount of synthetic oxytocin given during labor can be 5 to 10 IU, but lower and higher amounts of oxytocin may also be given. High-dose infusions of oxytocin may shorten the duration of labor by up to 2 hours compared with no infusion of oxytocin; however, it does not lower the frequency of cesarean delivery. When synthetic oxytocin is administered, the plasma concentration of oxytocin increases in a dose-dependent way: at infusion rates of 20 to 30 mIU/min, plasma oxytocin concentration increases approximately 2- to 3-fold above the basal level. Synthetic oxytocin administered at recommended dose levels is not likely to cross the placenta or maternal blood-brain barrier. Synthetic oxytocin should be administered with caution as high levels may induce tachystole and uterine overstimulation, with potentially negative consequences for the fetus and possibly the mother. Of note, 5 to 10 IU of synthetic oxytocin is often routinely given as an intravenous or intramuscular bolus administration after delivery to induce uterine contractility, which, in turn, induces uterine separation of the placenta and prevents postpartum hemorrhage. Furthermore, it promotes the expulsion of the placenta.

Considerable global demand exists for the development of novel drugs for the treatment of alopecia. A recent report demonstrated that oxytocin promotes hair growth activity in human dermal papilla (DP) cells; however, its application in drugs or cosmetic products is challenging because rapid degradation and relatively large molecular weight prevent long-term topical administration on the scalp. Here, we examined cinnamic acid, a small molecule activator for oxytocin receptor (OXTR) expression. Treatment with cinnamic acid led to upregulation of OXTR and trichogenic gene expression in human DP cells. Furthermore, inhibition of OXTR with an antagonist, L-371,257, suppressed hair growth-related gene expression in DP cells. These findings suggest that cinnamic acid enhances the hair growth ability of DP cells via oxytocin signaling. Additionally, we tested the hair growth-promoting effects of cinnamic acid using hair follicle organoids in vitro and observed that cinnamic acid significantly promoted the growth of hair peg-like sprouting. These promising results may be useful for developing hair growth-promoting products targeting oxytocin.

Diabetes insipidus (DI) is a group of disorders that lead to inappropriate production of large volumes of dilute urine. The three main forms are central DI (CDI), nephrogenic DI (NDI) and primary polydipsia (PP). Differentiating CDI/NDI from PP is important as patients with true DI are at risk of severe dehydration without treatment. Biochemical testing is key in the diagnosis of DI. The indirect water deprivation test (WDT) is commonly used in the investigation of DI but has drawbacks including being cumbersome and sometimes producing equivocal results. Direct measurement of AVP has theoretical advantages but has generally only been used in specialist centres. Disadvantages include the requirement to measure AVP under hypertonic stimulation and pre-analytical/analytical challenges. Copeptin (CT-proAVP) is a proxy marker for AVP that is more stable, easier to measure and has been studied more widely in recent years. Historically, the evidence supporting the diagnostic performance of these tests has been relatively poor, being based on a few small, usually single-centre studies. However more recent, well-designed prospective studies are improving the evidence base for investigation of DI. These studies have focused on the utility of copeptin measurements during stimulation tests. There is evidence that measurement of copeptin under stimulation offers improved diagnostic performance compared to the WDT. There is currently a lack of systematic, evidence-based guidelines on the diagnosis of DI, but as the quality of the evidence defining the diagnostic performance of tests for DI continues to improve, a clearer consensus on the optimal approach should become achievable.

Aim This official guideline was coordinated and published by the German Society of Gynaecology and Obstetrics (DGGG). The guideline aims to provide a consensus-based overview of the diagnosis and management of peripartum bleeding based on an evaluation of the relevant literature. Methods This S2k-guideline was developed by representative members from different medical professions on behalf of the guidelines commission of the DGGG, OEGGG and SGGG using a structured consensus process. Recommendations Recommendations for the definition, risk stratification, prevention, treatment (general emergency procedures, medications, uterine tamponade, surgical measures, interventional-radiological procedures, haemostasis, and coagulation management), transportation, documentation and debriefing as well as training are presented. In addition, a PPH algorithm for action, "PPH 2022", is recommended.

To examine the role of ex vivo oxytocin metabolism in post-dose peptide measurements.

The stability of oxytocin (Study 1) and oxytocinase activity (Study 2) in late-stage pregnancy blood was quantified using liquid-chromatography tandem mass-spectrometry (LC-MS/MS) and a fluorogenic assay, respectively. Analyses were conducted using blood from pregnant women (>36 weeks gestation) evaluated in lithium heparin (LH), ethylenediaminetetraacetic acid (EDTA) and BD P100 blood collection tubes with or without protease inhibitors. In addition, plasma oxytocin concentrations following administration of oxytocin 240 IU inhaled, 5 IU intravenous or 10 IU intramuscular in women in third stage of labour (TSL) were analysed using enzyme-linked immunosorbent assay (ELISA) and LC-MS/MS to understand how quantified peptide concentrations differ between these analytical methods (Study 3).

Study 1: Oxytocin was stable in blood collected into EDTA tubes with or without protease inhibitors but not in LH tubes. Study 2: Blood collected into all EDTA-containing collection tubes led to near-complete inhibition of oxytocinase (≤100 min). In plasma, a 35% reduction in oxytocinase activity was observed in LH tubes with EDTA added. In plasma from late-stage pregnancy compared to nonpregnant participants, the oxytocinase activity was approximately 11-fold higher. Study 3: Plasma oxytocin concentrations from nonpregnant or women in TSL following exogenous oxytocin administration were ≤33 times higher when analysed using ELISA vs. LC-MS/MS methods.

Collection of blood from late-stage pregnant women into tubes containing EDTA inhibits oxytocinase effectively stabilizing oxytocin, suggesting low concentrations of oxytocin after dose administration reflect rapid in vivo metabolism.

Social information gathering is a complex process influenced by neuroendocrine-modulated neural plasticity. Oxytocin (OXT) is a key regulator of social decision-making processes such as information gathering, as it contextually modulates social salience and can induce long-term structural plasticity, including neurogenesis. Understanding the link between OXT-induced plasticity and communicative awareness is crucial, particularly because OXT is being considered for treatment of social pathologies. We investigated the role of chronic OXT-dependent plasticity in attention to novel social information by manipulating the duration of time following cessation of intranasal treatment to allow for the functional integration of adult-born neurons resulting from OXT treatment. Following a 3-week delay, chronic intranasal OXT (IN-OXT) increased approach behavior of both female and male mice towards aggressive vocal playbacks of two unseen novel conspecifics, while no effect was observed after a 3-day delay. Immature neurons increased in the ventral hippocampus of females and males treated with chronic IN-OXT after the 3-week delay, indicating a potential association between ventral hippocampal neurogenesis and approach/acoustic eavesdropping. The less the mouse approached, the higher the level of neurogenesis. Contrary to expectations, the correlation between ventral hippocampal neurogenesis and approach behavior was not affected by IN-OXT, suggesting that other plasticity mechanisms underlie the long-term effects of chronic OXT on social approach. Furthermore, we found a negative correlation between ventral hippocampal neurogenesis and freezing behavior. Overall, our results demonstrate that chronic IN-OXT-induced long-term plasticity can influence approach to vocal information and we further reinforced the link between neurogenesis and anxiety.

Prematurity is a major risk factor for perinatal stress and neonatal complications leading to systemic inflammation and abnormal mother-infant interactions. Oxytocin (OT) is a neuropeptide regulating the inflammatory response and promoting mother-infant bonding. The release of this hormone might be influenced by either vocal or tactile stimulation. The main objective of the current randomized, crossover, clinical trial was to assess the salivary OT/cortisol balance in mothers following the exposure of their baby born preterm to two types of sensorial interventions: maternal voice without or with contingent tactile stimulation provided by the mother to her infant. Among the 26 mothers enrolled, maternal voice intervention alone had no effect on OT and cortisol levels in the mothers, but when associated with tactile stimulation, it induced a significant increase in maternal saliva oxytocin (38.26 ± 30.26 pg/mL before vs 53.91 ± 48.84 pg/mL after, p = 0.02), particularly in the mothers who delivered a female neonate. Maternal voice intervention induced a significant reduction in cortisol and an increase in OT levels in mothers when the maternal voice with a tactile stimulation intervention was performed first. In conclusion, exposure to the maternal voice with a contingent tactile stimulation was associated with subtle changes in the maternal hormonal balance between OT and cortisol. These findings need to be confirmed in a larger sample size and may ultimately guide caregivers in providing the best intervention to reduce parental stress following preterm delivery.

The relationship between copeptin and the severity of circulatory dysfunction and systemic stress response in patients with chronic liver disease (CLD) has been established. Nevertheless, the potential of serum copeptin levels to predict the prognosis of CLD patients remains unclear.

To conduct a systematic review and meta-analysis to investigate the correlation between serum copeptin and transplant-free survival (TFS) in this population.

To achieve the objective of the meta-analysis, PubMed, Embase, the Cochrane Library, and the Web of Science were searched to identify observational studies with longitudinal follow-up. The Cochrane Q test was utilized to assess between-study heterogeneity, and the I2 statistic was estimated. Random-effects models were employed to combine the outcomes, taking into account the potential influence of heterogeneity.

Ten datasets including 3133 patients were involved. The follow-up durations were 1 to 48 mo (mean: 12.5 mo). Overall, it was shown that a high level of serum copeptin was associated with a poor TFS [risk ratio (RR): 1.82, 95% confidence interval: 1.52-2.19, P < 0.001; I2 = 0%]. In addition, sensitivity analysis by omitting one dataset at a time showed consistent results (RR: 1.73-2.00, P < 0.05). Finally, subgroup analyses according to study country, study design, patient diagnosis, cutoff of copeptin, follow-up duration, and study quality score also showed similar results (P for subgroup difference all > 0.05).

Patients with CLD who have high serum copeptin concentrations may be associated with a poor clinical prognosis.

To evaluate the association between maternal body mass index (BMI) and plasma oxytocin (OT) levels at different OT infusion rates in labor.

A prospective observational study analyzing serial plasma samples in laboring women with OT infusion. The women were categorized into three groups, women with non-obesity (BMI 18.5-29.9, n = 12), obesity (BMI 30.0-34.9, n = 13), and morbid obesity (BMI ≥ 35.0, n = 15). Plasma OT was analyzed using tandem mass spectrometry.

Except for a low positive correlation between OT levels and BMI and significantly increased plasma OT levels in women with morbid obesity at the OT infusion rate of 3.3 mU/min, no significant differences in OT levels between the BMI groups were found. Further, the inter-individual differences in OT levels were large and no dose-dependent increase of OT levels was seen.

Other factors than plasma OT levels may be more likely to determine the clinical response of OT infusion in women with obesity. Perhaps the observed clinical need and individual response would be a better predictor of plasma OT levels than a pre-determined OT infusion rate. The OT dosage guidelines for labor augmentation should be individualized according to clinical response rather than generalized.

Clinical trial registration: ClinicalTrials.gov ID NCT04093479.

Oxytocin has traditionally been known for its physiological effects on muscle contraction associated with birth and lactation, but in the last years is widely used as a biomarker of "positive experiences" in psychology and behavior. Different types of samples have been used for oxytocin measurements with saliva samples having the particular advantage of an easy and non-stressful collection. However, the low concentration of oxytocin in saliva can represent a limitation for its use. For this reason, sensitive assays and even a previous sample treatment in some cases are required for saliva oxytocin quantification. In addition, the lack of standardized and generally agreed-upon approach to peripheral oxytocin measurement leads to large discrepancies between different laboratories, that use different sample treatment protocols and different assays. The main objectives of this review are to describe the current status of the use of saliva for oxytocin measurement, provide details of the different sample processing techniques that can be applied and inform about the analytical techniques and assays available in different animal species, and also in humans for comparative purposes. It is expected that this information can contribute to an increase in the knowledge about the measurements of oxytocin in saliva and to its wider use in the future.

Disruptions of the hypothalamic-pituitary axis can cause an arginine vasopressin deficiency, also known as central diabetes insipidus. Patients with this condition are at high risk of additional oxytocin deficiency owing to the close anatomical proximity of oxytocin-producing neurons; however, no conclusive evidence for such a deficiency has been reported. We aimed to use 3,4-methylenedioxymethamphetamine (MDMA, also known as ecstasy), a strong activator of the central oxytocinergic system, as a biochemical and psychoactive provocation test to investigate oxytocin deficiency in patients with arginine vasopressin deficiency (central diabetes insipidus).

This single-centre, case-control study with nested, randomised, double-blind, placebo-controlled crossover trial included patients with arginine vasopressin deficiency (central diabetes insipidus) and healthy controls (matched 1:1 by age, sex, and BMI) and was conducted at the University Hospital Basel, Basel, Switzerland. We used block randomisation to assign participants to receive either a single oral dose of MDMA (100 mg) or placebo in the first experimental session; patients received the opposite treatment at the next session, with a wash-out period of at least 2 weeks between the two sessions. Participants and investigators assessing the outcomes were masked to assignment. Oxytocin concentrations were measured at 0, 90, 120, 150, 180, and 300 min after MDMA or placebo. The primary outcome was the area under the plasma oxytocin concentration curve (AUC) after drug intake. The AUC was compared between groups and conditions using a linear mixed-effects model. Subjective drug effects were assessed throughout the study using ten-point visual analogue scales. Acute adverse effects were assessed before and 360 min after drug intake using a 66-item list of complaints. This trial is registered with ClinicalTrials.gov, NCT04648137.

Between Feb 1, 2021, and May 1, 2022, we recruited 15 patients with arginine vasopressin deficiency (central diabetes insipidus) and 15 healthy controls. All participants completed the study and were included in the analyses. In healthy controls, median plasma oxytocin concentration was 77 pg/mL (IQR 59-94) at baseline and increased by 659 pg/mL (355-914) in response to MDMA, resulting in an AUC of 102 095 pg/mL (41 782-129 565); in patients, baseline oxytocin concentration was 60 pg/mL (51-74) and only slightly increased by 66 pg/mL (16-94) in response to MDMA, resulting in an AUC of 6446 pg/mL (1291-11 577). The effect of MDMA on oxytocin was significantly different between groups: the AUC for oxytocin was 82% (95% CI 70-186) higher in healthy controls than in patients (difference 85 678 pg/mL [95% CI 63 356-108 000], p<0·0001). The increase in oxytocin in healthy controls was associated with typical strong subjective prosocial, empathic, and anxiolytic effects, whereas only minimal subjective effects were observed in patients, in agreement with the lack of increase in oxytocin concentrations. The most frequently reported adverse effects were fatigue (eight [53%] healthy controls and eight [53%] patients), lack of appetite (ten [67%] healthy controls and eight [53%] patients), lack of concentration (eight [53%] healthy controls and seven [47%] patients), and dry mouth (eight [53%] healthy controls and eight [53%] patients). In addition, two (13%) healthy controls and four (27%) patients developed transient mild hypokalaemia.

These findings are highly suggestive of clinically meaningful oxytocin deficiency in patients with arginine vasopressin deficiency (central diabetes insipidus), laying the groundwork for a new hypothalamic-pituitary disease entity.

Swiss National Science Foundation, Swiss Academy of Medical Sciences, and the G&J Bangerter-Rhyner Foundation.

The reproductive hormone oxytocin facilitates labour, birth and postpartum adaptations for women and newborns. Synthetic oxytocin is commonly given to induce or augment labour and to decrease postpartum bleeding.

To systematically review studies measuring plasma oxytocin levels in women and newborns following maternal administration of synthetic oxytocin during labour, birth and/or postpartum and to consider possible impacts on endogenous oxytocin and related systems.

Systematic searches of PubMed, CINAHL, PsycInfo and Scopus databases followed PRISMA guidelines, including all peer-reviewed studies in languages understood by the authors. Thirty-five publications met inclusion criteria, including 1373 women and 148 newborns. Studies varied substantially in design and methodology, so classical meta-analysis was not possible. Therefore, results were categorized, analysed and summarised in text and tables.

Infusions of synthetic oxytocin increased maternal plasma oxytocin levels dose-dependently; doubling the infusion rate approximately doubled oxytocin levels. Infusions below 10 milliunits per minute (mU/min) did not raise maternal oxytocin above the range observed in physiological labour. At high intrapartum infusion rates (up to 32 mU/min) maternal plasma oxytocin reached 2-3 times physiological levels. Postpartum synthetic oxytocin regimens used comparatively higher doses with shorter duration compared to labour, giving greater but transient maternal oxytocin elevations. Total postpartum dose was comparable to total intrapartum dose following vaginal birth, but post-caesarean dosages were higher. Newborn oxytocin levels were higher in the umbilical artery vs. umbilical vein, and both were higher than maternal plasma levels, implying substantial fetal oxytocin production in labour. Newborn oxytocin levels were not further elevated following maternal intrapartum synthetic oxytocin, suggesting that synthetic oxytocin at clinical doses does not cross from mother to fetus.

Synthetic oxytocin infusion during labour increased maternal plasma oxytocin levels 2-3-fold at the highest doses and was not associated with neonatal plasma oxytocin elevations. Therefore, direct effects from synthetic oxytocin transfer to maternal brain or fetus are unlikely. However, infusions of synthetic oxytocin in labour change uterine contraction patterns. This may influence uterine blood flow and maternal autonomic nervous system activity, potentially harming the fetus and increasing maternal pain and stress.

To evaluate the effect of delivery in a vertical birth chair (VBC) and traditional delivery table (DT) supported by women's movement during labor on the labor process, fetal outcome, maternal hormone levels, birth comfort, and satisfaction. This randomized controlled trial was conducted with 1:1:1 allocation. Group 1: in the VBC in upright position, Group 2: on the DT in supine position, these groups supported by freedom of movement, control group: on the DT in supine position, labor in bed. The duration of second stage of labor was not different between the groups (p = 0.246). The occurrence of instrumental birth, episiotomy, and perineal laceration was also not different among the groups (p = 0.772, p = 0.953, and p = 0.124). The use of uterotonic was observed in control group (p = 0.001). 1 and 5 APGAR scores of newborns were not different in all groups (p = 0.121, p = 0.268). The lowest pain score was observed in Group 1 (p = 0.001). Birth comfort and satisfaction were higher in Group 1 (p = 0.001 and p = 0.001). Decreased postpartum prolactin levels and increased postpartum oxytocin levels were observed in the control and Group 1 (p = 0.004, p = 0.006). Freedom of movement during labor and delivery using VBC in upright position can play birth-promoting and supporting role. There were no negative effects on the fetal outcome.

Older adults are increasingly lonely and at risk for hypertension. Endogenous oxytocin levels are associated with lowering blood pressure (BP), suggesting value in increasing oxytocin. Regular practice of Tai Chi improves BP and mood; we explored a single session of Tai Chi Easy (TCE) with older adults and feasibility of measuring oxytocin as a key biomarker.

In a single-arm pre-post design pilot study, 21 older adults (age 55-80) with mild-moderate hypertension practiced a single session (50-min) TCE. BP, psychosocial measures, and saliva samples were collected pre/post to examine feasibility of acute measures of oxytocin and explore effect sizes of outcomes. Participants (N = 21; 19 % Latinx, 76.2 % female, mean age 66.76).

BP systolic: 138.43-134.86; diastolic 78.48-78.00 (p > .05; Cohen's d -0.23; -0.08 respectively). Total Mood Disturbance (TMD) and Connection (CN) improved [TMD mean pre 41.891 (SD=19.60) to post 35.00 (SD=10.21), p = .01; Cohen's d - 0.67); CN mean 7.85 (SD=2.01) to post 9.05 (SD=1.00), p = .01; Cohen's d 0.70]. Baseline oxytocin was positively correlated with baseline loneliness (N = 14, r = .599); pre/post oxytocin changes were negatively correlated with baseline loneliness (N = 14, r = -.585). BP decrease was associated with characteristics of the intervention: "flow" (coef=.=0.58N = 17) and meditative/breath focus (coef=-1.78; N = 17).

Medium to large effect sizes indicating change in mood and connection were found for this single session intervention. Knowing that Tai Chi improves BP when practiced over time, this TCE intervention shows promise for planning a fully powered, randomized controlled study of BP, mood and perceptions of connection in hypertensive older adults. Feasibility of assessing acute salivary oxytocin is less promising. Increase in oxytocin levels occurred for those less lonely, but declined for lonelier participants. With different responses based on baseline loneliness scores, no mean change in oxytocin levels was found. Seemingly unstable levels (possibly related to interaction with study staff) suggests the need for further testing in more controlled study designs. Finally, BP associations with meditative/breath focus and flow could be further explored in future study designs addressing mediation.