Unlocking potential of oxytocin: improving intracranial lymphatic drainage for Alzheimer's disease treatment.

Background: The impediment to ß-amyloid (Aß) clearance caused by the invalid intracranial lymphatic drainage in Alzheimer's disease is pivotal to its pathogenesis, and finding reliable clinical available solutions to address this challenge remains elusive. Methods: The potential role and underlying mechanisms of intranasal oxytocin administration, an approved clinical intervention, in improving intracranial lymphatic drainage in middle-old-aged APP/PS1 mice were investigated by live mouse imaging, ASL/CEST-MRI scanning, in vivo two-photon imaging, immunofluorescence staining, ELISA, RT-qPCR, Western blotting, RNA-seq analysis, and cognitive behavioral tests. Results: Benefiting from multifaceted modulation of cerebral hemodynamics, aquaporin-4 polarization, meningeal lymphangiogenesis and transcriptional profiles, oxytocin administration normalized the structure and function of both the glymphatic and meningeal lymphatic systems severely impaired in middle-old-aged APP/PS1 mice. Consequently, this intervention facilitated the efficient drainage of Aß from the brain parenchyma to the cerebrospinal fluid and then to the deep cervical lymph nodes for efficient clearance, as well as improvements in cognitive deficits. Conclusion: This work broadens the underlying neuroprotective mechanisms and clinical applications of oxytocin medication, showcasing its promising therapeutic prospects in central nervous system diseases with intracranial lymphatic dysfunction.

Intramyometrial and intravenous oxytocin compared to intravenous carbetocin for prevention of postpartum hemorrhage in elective cesarean section-A quasi-randomized controlled phase IV non-inferiority interventional trial.

INTRODUCTION: Our objective was to assess non-inferiority of the unique approach used in our institution of combined 10 IU IM (intramyometrial) and 10 IU IV (intravenous) oxytocin to carbetocin IV in preventing severe postpartum blood loss in elective cesarean sections. The design was a prospective controlled phase IV non-inferiority interventional trial. The setting was a tertiary center at University Hospital, Zurich, Switzerland. MATERIAL AND METHODS: The population consisted of 550 women undergoing elective cesarean section after 36 completed weeks of gestation at low risk for postpartum hemorrhage (PPH). Participants were assigned to either combined oxytocin regimen (10 IU IM and 10 IU IV) or carbetocin (100 µg IV). Non-inferiority for oxytocin for severe PPH was assessed with a 0.05 margin using the Newcombe-Wilson score method. The main outcome measures were severe postpartum blood loss defined as delta hemoglobin (∆Hb, Hb prepartum-Hb postpartum) ≥30 g/L. RESULTS: Non-inferiority of combined oxytocin (IM/IV) in preventing severe postpartum blood loss was not shown (17 women in the oxytocin group vs. 7 in the carbetocin group). The number needed to treat when using carbetocin was 28. The risk difference for ∆Hb ≥30 g/L was 0.04 (oxytocin 0.06 vs. 0.03), 95% confidence interval (CI) (0.00-0.08). No significant difference was observed for ∆Hb (median 12 [IQR 7.0-19.0] vs. 11 [5.0-17.0], p = 0.07), estimated blood loss (median 500 [IQR 400-600] vs. 500 [400-575], p = 0.38), or the PPH rate defined as estimated blood loss ≥1000 mL (12[4.5] vs. 5 [2.0], risk difference 0.03, 95% CI (-0.01 to 0.06), p = 0.16). More additional uterotonics were administered in the oxytocin group compared to the carbetocin group (15.2% vs. 5.9%, p = 0.001). Total case costs were non-significantly different in the oxytocin group (US $ 10 146 vs. 9621, mean difference 471.4, CI (-476.5 to 1419.3), p = 0.33). CONCLUSIONS: Combined (IM/IV) oxytocin is not non-inferior to carbetocin regarding severe postpartum blood loss defined as postpartum Hb decrease ≥30 g/L in elective cesarean sections. We recommend carbetocin for use in clinical practice for elective cesarean sections.

Inpatient's, therapist's and staff's expectations regarding treatment and their effects on placebo response in the psychiatric ward - results from an add-on oxytocin RCT.

OBJECTIVES: Patient's and therapist's expectations are considered an important factor influencing placebo response in experimental and therapeutic settings. Nevertheless, the placebo effects of common neurological facilitators that promote treatment efficacy have not been explored. In the present study we examined the estimations of patients, therapists, and staff members, regarding their treatment type and assessed their influence on the facilitating effects of oxytocin. METHODS: Patients (N = 87) were randomized and double-blindly allocated to receive either oxytocin or placebo, twice daily for a period of four weeks, as part of a larger randomized, double-blind, placebo-controlled trial. Patient's, therapist's and staff's expectations were assessed based on their estimation of treatment type (agent or placebo). Multilevel modeling and univariate and multivariate regression analysis were performed to assess the effects of patient's, therapist's, and staff's estimations on treatment outcome beyond the effects of treatment type. RESULTS: Staff's, therapist's, and patient's estimations were significantly associated with treatment outcomes. Nevertheless, only therapist's and patient's estimations significantly predicted improvement beyond actual administration, with therapist's and patient's estimations associated with improvement in trait anxiety (STAI-T, B=-1.80, p < .05, and B=-2.02, p < .05, respectively); therapist's estimations were associated with improvement in general distress (OQ-45, B=-3.71, p < .05), and patient's estimations were associated with symptom relief (HSCL-11, B=-0.13, p < .05). Overall, patient's estimations had a higher relative contribution to treatment success, with standardized coefficients across scales ranging from - 0.06 to -0.26. CONCLUSIONS: The neurobiological factors that promote treatment success are also influenced by patient's and therapist's expectations. Future studies should consider these effects when examining their impact in inpatient settings.

Revealed masks: Facial mimicry after oxytocin administration in forensic psychopathic patients.

Facial mimicry serves as an evolutionarily rooted important interpersonal communication process that touches on the concepts of socialization and empathy. Facial electromyography (EMG) of the corrugator muscle and the zygomaticus muscle was recorded while male forensic psychopathic patients and controls watched morphed angry or happy facial expressions. We tested the hypothesis that psychopathic patients would show weaker short latency facial mimicry (that is, within 600 ms after stimulus onset) than controls. Exclusively in the group of 20 psychopathic patients, we tested in a placebo-controlled crossover within-subject design the hypothesis that oxytocin would enhance short-latency facial mimicry. Compared with placebo, we found no oxytocin-related significant short-latency responses of the corrugator and the zygomaticus. However, compared with 19 normal controls, psychopathic patients in the placebo condition showed significantly weaker short-latency zygomaticus responses to happy faces, while there was a trend toward significantly weaker short-latency corrugator responses to angry faces. These results are consistent with a recent study of facial EMG responses in adolescents with psychopathic traits. We therefore posit a lifetime developmental deficit in psychopathy pertaining short-latency mimicry of emotional facial expressions. Ultimately, this deficit in mimicking angry and happy expressions may hinder the elicitation of empathy, which is known to be impaired in psychopathy.

Impact of different obstetric interventions and types of delivery on breastfeeding: a nationwide cross-sectional survey of Hungarian women.

BACKGROUND: We assessed the effect of different obstetric interventions and types of delivery on breastfeeding. METHODS: A quantitative, cross-sectional study was carried out using an online questionnaire. Data collection was performed in 2021 in Hungary. We included biological mothers who had raised their at least 5-year-old child(ren) at home (N = 2,008). The questionnaire was completed anonymously and voluntarily. In addition to sociodemographic data (age, residence, marital status, education, occupation, income status, number of biological children, and anthropometric questions about the child and the mother), we asked about the interventions used during childbirth, and the different ways of infant feeding used. Statistical analysis was carried out using Microsoft Excel 365 and SPSS 25.0. Descriptive statistics, two-sample t tests, χ2 tests and ANOVA were used to analyse the relationship or differences between the variables (p < 0,05). RESULTS: We found that in deliveries where synthetic oxytocin was used for both induction and acceleration, there was a higher incidence of emergency cesarean section. However, the occurrence of vaginal deliveries was significantly higher in cases where oxytocin administration was solely for the purpose of accelerating labour (p < 0.001).Mothers who received synthetic oxytocin also received analgesics (p < 0.001). Women giving birth naturally who used oxytocin had a lower success of breastfeeding their newborn in the delivery room (p < 0.001). Children of mothers who received obstetric analgesia had a higher rate of complementary formula feeding (p < 0.001). Newborns born naturally had a higher rate of breastfeeding in the delivery room (p < 0.001) and less formula feeding in the hospital (p < 0.001). Infants who were breastfed in the delivery room were breastfed for longer periods (p < 0.001). Exclusive breastfeeding up to six months was longer for infants born naturally (p = 0.005), but there was no difference in the length of breastfeeding (p = 0.081). CONCLUSIONS: Obstetric interventions may increase the need for further interventions and have a negative impact on early or successful breastfeeding. TRIAL REGISTRATION: Not relevant.

Variations in the use of oxytocin for augmentation of labour in Sweden: a population-based cohort study.

National Swedish data shows substantial variation in the use of oxytocin for augmentation of spontaneous labour between obstetric units. This study aimed to investigate if variations in the use of oxytocin augmentation are associated with maternal and infant characteristics or clinical factors. We used a cohort design including women allocated to Robson group 1 (nulliparous women, gestational week ≥ 37 + 0, with singleton births in cephalic presentation and spontaneous onset of labour) and 3 (parous women, gestational week ≥ 37 + 0, with singleton births in cephalic presentation, spontaneous onset of labour, and no previous caesarean birth). Crude and adjusted logistic regression models with marginal standardisation were used to estimate risk ratios (RR) and risk differences (RD) with 95% confidence intervals (CI) for oxytocin use by obstetric unit. An interaction analysis was performed to investigate the potential modifying effect of epidural. The use of oxytocin varied between 47 and 73% in Robson group 1, and 10% and 33% in Robson group 3. Compared to the remainder of Sweden, the risk of oxytocin augmentation ranged from 13% lower (RD - 13.0, 95% CI - 15.5 to - 10.6) to 14% higher (RD 14.0, 95% CI 12.3-15.8) in Robson group 1, and from 6% lower (RD - 5.6, 95% CI - 6.8 to - 4.5) to 18% higher (RD 17.9, 95% CI 16.5-19.4) in Robson group 3. The most notable differences in risk estimates were observed among women in Robson group 3 with epidural. In conclusion, variations in oxytocin use remained despite adjusting for risk factors. This indicates unjustified differences in use of oxytocin in clinical practice.

A clustering approach identifies an Autism Spectrum Disorder subtype more responsive to chronic oxytocin treatment.

Over the last decade, a number of clinical trials have reported effects of chronic treatment with intranasal oxytocin on autistic symptoms but with inconsistent findings. Autism is a heterogeneous disorder and one factor which may influence treatment outcome is whether a subtype of individuals is more sensitive to oxytocin. In a recent cross-over trial on 41 young autistic children we reported that 44% showed a reliable improvement in clinical symptoms (Autism Diagnostic Observation Schedule, ADOS-2) after a placebo-controlled, 6-week intranasal oxytocin intervention where treatment was given every other day followed by a period of positive social interaction. In the current re-assessment of the data, we used an unsupervised data-driven cluster analysis approach to identify autism subtypes using 23 different demographic, social subtype, endocrine, eye-tracking and clinical symptom measures taken before treatment and this revealed an optimum of two different subtypes. We then assessed the proportion of identified responders to oxytocin and found that while 61.5% of one subtype included responders only 13.3% of the other did so. During the placebo phase there was no difference between the two subtypes for the small proportion of responders (19.2% vs 6.7%). This oxytocin-sensitive subtype also showed overall significant post-treatment clinical and eye-tracking measure changes. The oxytocin-sensitive subtype was primarily characterized at baseline by lower initial clinical severity (ADOS-2) and greater interest in the eye-region of emotional faces. These features alone were nearly as efficient in identifying the two subtypes as all 23 baseline measures and this easy-to-conduct approach may help rapidly and objectively screen for oxytocin responders. Future clinical trials using oxytocin interventions may therefore achieve greater success by focusing on children with this specific autism subtype and help develop individualized oxytocin intervention.

Patterns of oxytocin use for induction and augmentation of labour among healthcare providers in Nigeria.

BACKGROUND: The practice of intrapartum use of oxytocin for induction and augmentation of labour is increasing worldwide with documented wide variations in clinical use, especially dose administrations. There is also evidence of intrapartum use by unauthorized cadre of staff. AIM: This study assessed the patterns - frequency of intrapartum use of oxytocin, the doses and routes of administration for induction and augmentation of labour, and identified the predictors of oxytocin use for induction and augmentation of labour by healthcare providers in Nigeria. METHODS: This was a cross-sectional study conducted among healthcare providers - doctors, nurses/midwives and community health workers (CHWs) in public and private healthcare facilities across the country's six geopolitical zones. A multistage sampling technique was used to select 6,299 eligible healthcare providers who use oxytocin for pregnant women during labour and delivery. A self-administered questionnaire was used to collect relevant data and analysed using STATA 17 statistical software. Summary and inferential statistics were done and further analyses using multivariable regression models were performed to ascertain independent predictor variables of correct patterns of intrapartum oxytocin usage. The p-value was set at < 0.05. RESULTS: Of the 6299 respondents who participated in the study, 1179 (18.7%), 3362 (53.4%), and 1758 (27.9%) were doctors, nurses/midwives and CHWs, respectively. Among the respondents, 4200 (66.7%) use oxytocin for augmentation of labour while 3314 (52.6%) use it for induction of labour. Of the 1758 CHWs, 37.8% and 49% use oxytocin for induction and augmentation of labour, respectively. About 10% of the respondents who use oxytocin for the induction or augmentation of labour incorrectly use the intramuscular route of administration and about 8% incorrectly use intravenous push. Being a doctor, and a healthcare provider from government health facilities were independent positive predictors of the administration of correct dose oxytocin for induction and augmentation of labour. The CHWs were most likely to use the wrong route and dose administration of oxytocin for the induction and augmentation of labour. CONCLUSION: Our study unveiled a concerning clinical practice of intrapartum oxytocin use by healthcare providers in Nigeria - prevalence of intrapartum use of oxytocin, inappropriate routes of administration for induction and augmentation of labour, varied and inappropriately high start dose of administration including unauthorized and high intrapartum use of oxytocin among CHWs.

Association of oxytocin augmentation with postpartum hemorrhage: a systematic review and meta-analysis.

OBJECTIVE: The current study aims to evaluate the correlation between oxytocin augmentation and postpartum hemorrhage. METHOD: PubMed, Web of Science, and Scopus has been searched for studies assessing the correlation between oxytocin augmentation and postpartum hemorrhage up to January 24, 2024. The search strategy included relevant keywords related to PPH and oxytocin augmentation. The risk of bias assessment was conducted by two reviewers using the Newcastle-Ottawa Scale (NOS). To pool the effects sized of included studies odds ratios (OR) of interest outcome with their 95% confidence interval (CI) were used. RESULTS: Eight studies were included in this meta-analysis. The pooled analysis of the included studies showed a statistically significant association between oxytocin augmentation and increased odds of PPH (pooled odds ratio [OR] = 1.27, 95% confidence interval [CI]: 1.05-1.53; I2 = 84.94%; p = 0.01). Publication bias was assessed using funnel plots, which appeared relatively asymmetrical, indicating significant publication bias. Galbraith plot and trim and fill plot were used for publication bias. Sensitivity analyses were performed by leave one out method. CONCLUSION: This meta-analysis suggests that using oxytocin for labor augmentation is linked to a significant increase in the risk of PPH. It highlights the need for careful monitoring and consideration when using oxytocin, especially in low and middle-income countries where guidelines and supervision are crucial.

The interplay of oxytocin and sex hormones.

The neuropeptide oxytocin has historically been associated with reproduction and maternal behavior. However, more recent research has uncovered that oxytocin has a much wider range of roles in physiology and behavior. Despite the excitement surrounding potential therapeutical applications of intranasally administered oxytocin, the results of these intervention studies have been inconsistent. Various reasons for these mixed results have been proposed, which tend to focus on methodological issues, such as study design. While methodological issues are certainly important, emerging evidence suggests that the interaction between oxytocin and sex hormones may also account for these varied findings. To better understand the purpose and function of the interaction of oxytocin with sex hormones, with a focus on estrogens, progesterone, and testosterone, we conducted a comprehensive thematic review via four perspectives: evolutionary, developmental, mechanistic, and survival. Altogether, this synergistic approach highlights the critical function of sex hormone activity for accomplishing the diverse roles of oxytocin via the modulation of oxytocin release and oxytocin receptor activity, which is also likely to contribute to the heterogeneity of outcomes after oxytocin administration.

Effect of administration routes of oxytocin on hemoglobin in neonates with delayed umbilical cord clamping: a multi-centre randomized controlled clinical trial.

PURPOSE: To evaluate the effect of intravenous infusion versus intramyometrial injection of oxytocin on hemoglobin levels in neonates with delayed umbilical cord clamping during cesarean section. METHODS: The multi-centre randomized controlled trial was performed at three hospitals from February to June 2023. Women with term singleton gestations scheduled for cesarean delivery were allocated to receive an intravenous infusion of 10 units of oxytocin or a myometrial injection of 10 units of oxytocin during the surgery. The primary outcome was neonatal hemoglobin at 48 to 96 h after birth. Secondary outcomes were side-effects of oxytocin, postpartum haemorrhage, phototherapy for jaundice, feeding at 1 month, maternal and neonatal morbidity and re-admissions. RESULTS: A total of 360 women were randomized (180 women in each group). The mean neonatal hemoglobin did not show a significant difference between the intravenous infusion group (194.3 ± 21.7 g/L) and the intramyometrial groups (195.2 ± 24.3 g/L) (p = 0.715). Secondary neonatal outcomes, involving phototherapy for jaundice, feeding at 1 month and neonatal intensive care unit admission were similar between the two groups. The maternal outcomes did not differ significantly between the two groups, except for a 200 mL higher intraoperative infusion volume observed in the intravenous group compared to the intramyometrial group. CONCLUSION: Among women undergoing elective cesarean delivery of term singleton pregnancies, there was no significant difference in neonatal hemoglobin at 48 to 96 h after birth between infants with delayed cord clamping, whether the oxytocin was administrated by intravenous infusion or intramyometrial injection. TRIAL REGISTRATION: Chinese Clinical trial registry: ChiCTR2300067953 (1 February 2023).

The effects of oxytocin administration on social and routinized behaviors in autism: A preregistered systematic review and meta-analysis.

Oxytocin administration has demonstrated considerable promise for providing individualized support for autistic people. However, studies evaluating the effects of oxytocin administration on autistic characteristics have yielded inconsistent results. This systematic review and meta-analysis investigates the effect of oxytocin administration on social and routinized behaviors in autism using recently developed methods to accurately assess the potential impact of effect size dependency and publication bias. Our frequentist meta-analysis yielded a significant summary effect size estimate for the impact of oxytocin administration on social outcomes in autism (d = 0.22, p < 0.001). The summary effect size estimate for routinized behavior outcomes was not statistically significant (d = 0.14, p = 0.22), with a follow up test indicating that the effect size estimate was not either statistically equivalent (Z = -1.06, p = 0.2), assuming a smallest effect size of interest of 0.25. Frequentist and Bayesian assessments for publication bias, as well as results from Robust Bayesian meta-analysis of oxytocin effects on social outcomes in autism, indicated that summary effect sizes might be inflated due to publication bias. Future studies should aim to reduce bias by preregistering analysis plans and to increase precision with larger sample sizes.

The impact of oxytocin on emotion recognition and trust: Does disordered eating moderate these relationships?

OBJECTIVES: The current study aimed to investigate the impact of oxytocin on emotion recognition, trust, body image, affect, and anxiety and whether eating disorder (ED) symptoms moderated any of these relationships. METHOD: Participants (n = 149) were female university students, who were randomly allocated to receive in a double-blind nature, a single dose of oxytocin intranasal spray (n = 76) or a placebo (saline) intranasal spray (n = 73). Participants were asked to complete an experimental measure of emotion recognition and an investor task aimed to assess trust. RESULTS: The oxytocin group exhibited better overall performance on the emotion recognition task (especially with recognising positive emotions), and a decline in state positive affect than the control group at post-intervention. However, these effects were not moderated by ED symptom severity, nor were effects found for state anxiety, negative affect, body image and recognising negative emotions in the emotion recognition task. CONCLUSION: The current findings contribute to the growing literature on oxytocin, emotion recognition and positive affect and suggest that ED pathology does not moderate these relationships. Future research would benefit from examining the efficacy of an oxytocin intervention using a within-subjects, cross-over design, in those with sub-clinical and clinical EDs, as well as healthy controls.

Oxytocin-Augmented Modular-Based Group Intervention for Loneliness: A Proof-Of-Concept Randomized Controlled Trial.

INTRODUCTION: Loneliness poses a significant health problem and existing psychological interventions have shown only limited positive effects on loneliness. Based on preliminary evidence for impaired oxytocin signaling in trait-like loneliness, the current proof-of-concept study used a randomized, double-blind, placebo-controlled design to probe intranasal oxytocin (OT) as an adjunct to a short-term modular-based group intervention for individuals suffering from high trait-like loneliness (HL, UCLA Loneliness Scale ≥55). METHODS: Seventy-eight healthy HL adults (56 women) received five weekly group psychotherapy sessions. HL participants received OT or placebo before the intervention sessions. Primary outcomes were trait-like loneliness measured at baseline, after the intervention, and again at two follow-up time points (3 weeks and 3 months), and, assessed at each session, state loneliness (visual analog scale), perceived stress (Perceived Stress Scale, PSS-10), quality of life (World Health Organization Five Well-Being Index, WHO-5), and the therapeutic relationship (Group Questionnaire, GQ-D). RESULTS: The psychological intervention was associated with significantly reduced perceived stress and improved trait-like loneliness across treatment groups, which was still evident at the 3-month follow-up. OT had no significant effect on trait-like loneliness, quality of life, or perceived stress. However, compared to placebo, OT significantly facilitated the decrease in state loneliness within sessions and significantly improved positive bonding between the group members. CONCLUSION: Despite significantly improved trait-like loneliness after the intervention, OT did not significantly augment this effect. Further studies are needed to determine optimal intervention designs to translate the observed acute effects of OT into long-term benefits.

Administration of Atosiban, an oxytocin receptor antagonist, ameliorates autistic-like behaviors in a female rat model of valproic acid-induced autism.

Autism spectrum disorder (ASD) is a pervasive developmental disorder with gender differences. Oxytocin (OXT) is currently an important candidate drug for autism, but the lack of data on female autism is a big issue. It has been reported that the effect of OXT is likely to be different between male and female ASD patients. In the study, we specifically explored the role of the OXT signaling pathway in a VPA-induced female rat's model of autism. The data showed that there was an increase of either oxytocin or its receptor expressions in both the hippocampus and the prefrontal cortex of VPA-induced female offspring. To determine if the excess of OXT signaling contributed to autism symptoms in female rats, exogenous oxytocin and oxytocin receptor antagonists Atosiban were used in the experiment. It was found that exogenous oxytocin triggered autism-like behaviors in wild-type female rats by intranasal administration. More interestingly, several autism-like deficits including social interaction, anxiety, and repeat stereotypical sexual behavior in the VPA female offspring were significantly attenuated by oxytocin receptor antagonists Atosiban. Moreover, Atosiban also effectively improved the synaptic plasticity impairment induced by VPA in female offspring. Our results suggest that oxytocin receptor antagonists significantly improve autistic-like behaviors in a female rat model of valproic acid-induced autism.

Intranasal Oxytocin for Obesity.

BACKGROUND: Accumulating preclinical and preliminary translational evidence shows that the hypothalamic peptide oxytocin reduces food intake, increases energy expenditure, and promotes weight loss. It is currently unknown whether oxytocin administration is effective in treating human obesity. METHODS: In this randomized, double-blind, placebo-controlled trial, we randomly assigned adults with obesity 1:1 (stratified by sex and obesity class) to receive intranasal oxytocin (24 IU) or placebo four times daily for 8 weeks. The primary end point was change in body weight (kg) from baseline to week 8. Key secondary end points included change in body composition (total fat mass [g], abdominal visceral adipose tissue [cm2], and liver fat fraction [proportion; range, 0 to 1; higher values indicate a higher proportion of fat]), and resting energy expenditure (kcal/day; adjusted for lean mass) from baseline to week 8 and caloric intake (kcal) at an experimental test meal from baseline to week 6. RESULTS: Sixty-one participants (54% women; mean age ± standard deviation, 33.6 ± 6.2 years; body-mass index [the weight in kilograms divided by the square of the height in meters], 36.9 ± 4.9) were randomly assigned. There was no difference in body weight change from baseline to week 8 between oxytocin and placebo groups (0.20 vs. 0.26 kg; P=0.934). Oxytocin (vs. placebo) was not associated with beneficial effects on body composition or resting energy expenditure from baseline to week 8 (total fat: difference [95% confidence interval], 196.0 g [-1036 to 1428]; visceral fat: 3.1 cm2 [-11.0 to 17.2]; liver fat: -0.01 [-0.03 to 0.01]; resting energy expenditure: -64.0 kcal/day [-129.3 to 1.4]). Oxytocin compared with placebo was associated with reduced caloric intake at the test meal (-31.4 vs. 120.6 kcal; difference [95% confidence interval], -152.0 kcal [-302.3 to -1.7]). There were no serious adverse events. Incidence and severity of adverse events did not differ between groups. CONCLUSIONS: In this randomized, placebo-controlled trial in adults with obesity, intranasal oxytocin administered four times daily for 8 weeks did not reduce body weight. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT03043053.).

Gluco-metabolic response to exogenous oxytocin in totally pancreatectomized patients and healthy individuals.

Oxytocin has been proposed to possess glucose-stabilizing effects through the release of insulin and glucagon from the pancreas. Also, exogenous oxytocin has been shown to stimulate extrapancreatic glucagon secretion in depancreatized dogs. Here, we investigated the effect of exogenous oxytocin on circulating levels of pancreatic and gut-derived glucose-stabilizing hormones (insulin [measured as C-peptide], glucagon, glucagon-like peptide 1 [GLP-1], and glucose-dependent insulinotropic polypeptide). We studied nine pancreatectomized (PX) patients and nine healthy controls (CTRLs) (matched on age and body mass index) before, during, and after an intravenous infusion of 10 IU of oxytocin administered over 12 min. Oxytocin did not increase plasma glucagon levels, nor induce any changes in plasma glucose, C-peptide, or GIP in any of the groups. Oxytocin decreased plasma glucagon levels by 19 ± 10 % in CTRLs (from 2.0 ± 0.5 [mean ± SEM] to 1.3 ± 0.2 pmol/l, P = 0.0025) and increased GLP-1 by 42 ± 22 % in PX patients (from 9.0 ± 1.0-12.7 ± 1.0 pmol/l, P = 0.0003). Fasting plasma glucose levels were higher in PX patients compared with CTRLs (13.1 ± 1.1 vs. 5.1 ± 0.1 mmol/l, P < 0.0001). In conclusion, the present findings do not support pancreas-mediated glucose-stabilizing effects of acute oxytocin administration in humans and warrant further investigation of oxytocin's gluco-metabolic effects.

Intranasal oxytocin suppresses seizure-like behaviors in a mouse model of NGLY1 deficiency.

NGLY1 deficiency is a genetic disease caused by biallelic mutations of the Ngly1 gene. Although epileptic seizure is one of the most severe symptoms in patients with NGLY1 deficiency, preclinical studies have not been conducted due to the lack of animal models for epileptic seizures in NGLY1 deficiency. Here, we observed the behaviors of male and female Ngly1-/- mice by video monitoring and found that these mice exhibit spontaneous seizure-like behaviors. Gene expression analyses and enzyme immunoassay revealed significant decreases in oxytocin, a well-known neuropeptide, in the hypothalamus of Ngly1-/- mice. Seizure-like behaviors in Ngly1-/- mice were transiently suppressed by a single intranasal administration of oxytocin. These findings suggest the therapeutic potential of oxytocin for epileptic seizure in patients with NGLY1 deficiency and contribute to the clarification of the disease mechanism.

Social functioning predicts individual changes in EEG microstates following intranasal oxytocin administration: A double-blind, cross-over randomized clinical trial.

Oxytocin (OXT) modulates social behaviors. However, the administration of exogenous OXT in humans produces inconsistent behavioral changes, affecting future consideration of OXT as a treatment for autism and other disorders with social symptoms. Inter-individual variability in social functioning traits might play a key role in how OXT changes brain activity and, therefore, behavior. Here, we investigated if inter-individual variability might dictate how single-dose intranasal OXT administration (IN-OXT) changes spontaneous neural activity during the eyes-open resting state. We used a double-blinded, randomized, placebo-controlled, cross-over design on 30 typically developing young adult men to investigate the dynamics of EEG microstates corresponding to activity in defined neural networks. We confirmed previous reports that, at the group level, IN-OXT increases the representation of the attention and salience microstates. Furthermore, we identified a decreased representation of microstates associated with the default mode network. Using multivariate partial least square statistical analysis, we found that social functioning traits associated with IN-OXT-induced changes in microstate dynamics in specific spectral bands. Correlation analysis further revealed that the higher the social functioning, the more IN-OXT increased the appearance of the visual network-associated microstate, and suppressed the appearance of a default mode network-related microstate. The lower the social functioning, the more IN-OXT increases the appearance of the salience microstate. The effects we report on the salience microstate support the hypothesis that OXT regulates behavior by enhancing social salience. Moreover, our findings indicate that social functioning traits modulate responses to IN-OXT and could partially explain the inconsistent reports on IN-OXT effects.

Intrapartum pyrexia, cardiotocography traces and histologic chorioamnionitis: a case-control study.

OBJECTIVES: To compare characteristics of labor, cardiotocography traces, and maternal and neonatal outcomes, in a cohort of pregnancies at term complicated by maternal intrapartum pyrexia, with or without a histologic diagnosis of chorioamnionitis. METHODS: This is a retrospective case-control study including pregnancies at term with detection of maternal intrapartum pyrexia, delivered between January 2020 and June 2021. Cardiotocography traces were entirely evaluated, since admission till delivery, and classified according to the International Federation of Obstetrics and Gynecology (FIGO) guideline. Maternal and neonatal outcomes were also recorded as secondary outcomes. Placentas have been studied according to the Amniotic Fluid Infection Nosology Committee. RESULTS: Forty four patients met the inclusion criteria and were included in the study cohort. There was a significant association between the use of oxytocin augmentation in labor and the histologic diagnosis of chorioamnionitis. A significative recurrence of loss and/or absence of accelerations at the point of pyrexia was also documented in women with histological chorioamnionitis compared to the others. CONCLUSIONS: Chorioamnionitis appears to be associated with myometrial disfunction, as suggested by the increased use of oxytocin augmentation during active labor of women at term with intrapartum pyrexia and histologic diagnosis of chorioamnionitis.