Background Postpartum depression (PPD) is common and can impair early mother-infant bonding. Oxytocin (OXT) supports socioemotional adaptation, yet intranasal OXT yields supraphysiological exposure and mixed results. The probiotic Limosilactobacillus reuteri (L. reuteri) increases endogenous oxytocin levels in rodents, suggesting that it may enhance OXT signaling via gut-brain pathways in humans. We designed a proof-of-concept trial to test whether postpartum L. reuteri improves early mother-infant bonding and maternal mental health, impulse control, and emotion recognition. Methods In this randomized, double-blind, placebo-controlled trial, mothers aged ≥18 years at elevated PPD risk (history of depression, prior PPD, and/or increased prenatal depressive symptoms) received 6 weeks of once-daily L. reuteri or placebo, stratified by delivery mode (vaginal/Cesarean section). The primary endpoint is mother-infant bonding quality at Week 6; secondary endpoints include maternal mental health, impulse control, and emotion recognition at Week 6. Salivary OXT at Week 2 serves as a mechanistic endpoint. Results Forty-six participants (mean age ± SD: 34.3 ± 4.5 years) were enrolled and randomized; 38 (82.6%) completed the Week-6 visit. Baseline characteristics are reported. Conclusion This trial evaluates whether a lactation-compatible L. reuteri intervention targeting endogenous OXT improves early mother-infant bonding and maternal well-being. Findings will inform feasibility, safety, and effect size estimates, clarify OXT's mechanistic role in PPD pathophysiology, and guide development of microbiome-based therapeutics for perinatal mental health. Trial registration number ClinicalTrials.gov: NCT04472065.

Parent-infant synchrony during social interaction exerts a critical influence on the healthy development of children. There is limited understanding of how synchrony may be influenced by mothers' history of childhood adversity. We evaluated the efficacy of a behavioral intervention, Massage+, on mother-infant synchrony among first-time mothers with childhood adversity. Adult pregnant women with adverse childhood experiences scores of ≥ 2 were enrolled in this longitudinal study. At birth, mothers and their full-term infants (N = 213) were randomized to the Massage+ group or the attention control group learning safe infant care. Mothers performed daily Massage+, which included talking to their infants, moderate touch stroking, looking at, and rocking their infant. At 3 months, mother-infant synchrony was microcoded for gaze, affect, vocalization, and touch from video recordings of a free-play interaction (N = 162). Compared with control dyads, the Massage+ dyads exhibited more co-occurring affect synchrony, touch synchrony, and maternal engagement with high infant arousal synchrony. Massage+ dyads also exhibited more sequential synchrony and faster time-to-first initiation of synchrony. When infants expressed positive arousal, Massage+ dyads were better able to increase the amount of synchrony, coordinate synchrony by mothers immediately responding to their infant's positive cues, and more quickly settle into synchrony. Encouraging positive affect is among the most critical early functions of synchrony. Future research warrants studying long-term benefits of Massage+ when implemented in real-world settings. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

In an era marked by rising stress-related disorders and cardiovascular morbidity, understanding how the brain and heart adapt to environmental, physiological, and social stressors has become an urgent biomedical priority. This review advances an integrative framework centered on sociostasis, defined as the dynamic regulation of physiological state through social interaction, and its intersection with hormesis, a biphasic adaptive response to controlled stress that enhances resilience. We focus on four evolutionarily conserved neuropeptides, vasopressin, oxytocin, corticotropin-releasing hormone, and the urocortins, which serve as molecular bridges linking social behavior, neuroendocrine signaling, autonomic regulation, and cardiovascular function. Operating within an organized autonomic architecture, these systems calibrate responses to acute and chronic stress. Their context-dependent synergy enables adaptive flexibility under manageable challenge but may promote maladaptive cardiovascular remodeling when chronically dysregulated. Genetic vulnerability, developmental adversity, and persistent psychosocial stress can shift neuroendocrine–autonomic set points, increasing susceptibility to hypertension, endothelial dysfunction, and stress-induced cardiomyopathy. Conditioning and preconditioning paradigms illustrate how repeated exposure to subthreshold stressors primes cardiovascular tissues for future insults, enhancing ischemic tolerance and adaptive gene expression. We propose that cardiovascular hormesis depends not only on stimulus intensity but also on the integrity of neuroautonomic regulatory mechanisms that support recovery and flexibility. Vagal efficiency, a dynamic index of cardioinhibitory regulation, is discussed as a potential translational metric of adaptive capacity. By integrating molecular, physiological, and psychosocial perspectives, this framework conceptualizes cardiovascular resilience as an emergent property of coordinated hormetic signaling, neuropeptidergic modulation, autonomic regulation, and social buffering. Translational implications include peptide-based therapies, autonomic biofeedback, and behavioral interventions designed to enhance stress adaptability.

We thank Lago and Bolognani [...].

Oxytocin has emerged as a pivotal modulator of human social behavior, yet its effects are embedded within a broader hypothalamic neuropeptidergic network that also includes vasopressin, corticotropin-releasing hormone (CRH), orexin, and neuropeptide Y (NPY). These evolutionarily conserved systems jointly regulate socioaffective resonance - the dynamic alignment of emotional, physiological, and cognitive states between individuals - by tuning social salience, arousal, affective simulation, and stress regulation. Here, we synthesize evidence from animal and human research to outline an integrative model in which oxytocin’s effects are amplified, attenuated, or redirected by the state of these other peptide systems. We introduce the Socioaffective Resonance Collapse Hypothesis, proposing that transdiagnostic social impairments in conditions such as autism, borderline personality disorder, depression, and schizophrenia may reflect maladaptive neuropeptide configurations that destabilize interpersonal alignment. By embedding oxytocin within this multi-system framework, we identify novel pathways for precision interventions, including pharmacological and behavioral strategies aimed at restoring the neurochemical balance that supports social connection. This conceptual synthesis complements oxytocin-focused perspectives by clarifying when and why oxytocin-based interventions may succeed or fail, and by offering a roadmap for translating basic neuropeptide science into clinical applications.

The authors would like to make the following correction to their published paper [...]

BACKGROUND:Exogenous oxytocin (OT) reduces reward-driven food intake. Less is known about endogenous OT and eating behaviour. Preclinical studies suggest peripheral OT levels may reflect the opposite of central appetite-related OT activity. In healthy females, circulating OT declines after eating. Whether this pattern exists in obesity and how endogenous OT relates to hedonic eating remains unclear. We hypothesised that OT would decrease postprandially in adults with obesity and that higher OT exposure, reflecting lower central OT signalling, would correlate with greater reward-driven caloric intake. METHODS:Sixty-one adults with obesity (56% female; age [mean ± SE] 33.55 ± 0.81 years; BMI 36.77 ± 0.62 kg/m2) consumed a standardised meal following an overnight fast. OT was measured in peripheral blood pre-meal and 30, 60, and 120 min post-meal. Area under the curve (AUC) was calculated to capture OT exposure. Postprandial hedonic eating drive was assessed via visual analogue scales (VAS) and Cookie Taste Test (CTT). Meal-related OT dynamics were analysed using linear mixed effects models, relationships between OT exposure and hedonic eating drive were examined with linear regression and mediation analyses. RESULTS:OT levels did not change in response to the meal. Greater OT AUC was associated with reduced postprandial satisfaction (p = 0.008, d = 1.00) and higher CTT caloric intake (p = 0.036, d = 0.62). The relationship between OT AUC and CTT caloric intake was mediated by OT's effect on postprandial satisfaction (p = 0.014, proportion mediated = 53.28%). CONCLUSIONS:In obesity, OT levels did not change postprandially. Greater OT exposure was linked to lower satisfaction and increased hedonic eating, suggesting dysregulated OT signalling in obesity potentially contributing to overeating.

Background A clinically significant oxytocin-deficient state (OXT-D) has been established in adults with arginine vasopressin deficiency, and there is a need to develop diagnostic testing. Kisspeptin (KP) is a candidate for such a test, as KP receptors are found on oxytocinergic neurons, and KP administration increases plasma OXT in animals. We hypothesized that intravenous KP administration would increase peripheral OXT levels post-injection in healthy adults.Methods Kisspeptin-112-121 (KP analog, 0.24 nmol/kg bolus) was administered to 12 healthy adults (50% female). Serum OXT was measured before and 10, 20, 40, and 60 min after KP administration.Results Males and females did not differ significantly in age, BMI, or baseline OXT levels. Ten minutes after KP, OXT increased by 18.8% from baseline (FDR-P = .004) with a greater increase in males than females (31.9% vs 5.7%, respectively, FDR-P = .004).Conclusions Our data support KP as a candidate for a provocative test to identify OXT-D in males.Clinical trial registration Our study was registered on ClinicalTrials.gov (NCT00914823).

To date, nearly one in three births in the United States occurs after a labor induced with synthetic oxytocin. Despite how common this intervention is, little is known about its long-term consequences for maternal health. Existing work has identified a link between labor induction with synthetic oxytocin and increased risk for postpartum depression. For some women, the link between labor induction and postpartum depression risk may be altered functioning of the oxytocin system, including epigenetic modification of the oxytocin receptor gene, OXTR. Here we use the prairie vole to understand how pregnancy and birth impact epigenetic control of Oxtr, and how a labor induced with synthetic oxytocin may alter this control. In an unmanipulated birth model, we measured Oxtr DNA methylation levels in the brain of virgin females, at term pregnancy, and 90 min postpartum using targeted pyrosequencing at four CpG sites in the Oxtr promotor region that are conserved from the human OXTR. We used RT-PCR to assess Oxtr gene expression levels in the brains of these same subjects. These same methods were next used in a model of labor induction with exogenous oxytocin. In both models, brain regions targeted for analysis included the nucleus accumbens, amygdala, and medial preoptic area. These regions all use oxytocin system activity in regulating aspects of maternal behaviors. 2-way ANOVA, unpaired two-tailed t-tests, and Pearson’s and Spearman’s correlations were used for analyses. Results identify a regulatory switch in Oxtr from term pregnancy to early postpartum that is facilitated in part by oxytocin. Oxtr DNA methylation in virgins is negatively associated with Oxtr gene expression at all four conserved CpG sites in the nucleus accumbens. At term pregnancy, there is no relationship between these markers. Immediately postpartum, this relationship shifts back to a pre-pregnancy state. Administration of increasing doses of exogenous oxytocin, modeling labor induction, shifts the methylation-expression relationship toward a negative state in the nucleus accumbens, mimicking a postnatal brain but at a prenatal time point. Findings show epigenetic control of Oxtr is dynamic across pregnancy and birth and is sensitive to exogenous oxytocin. Results indicate a need to better understand how common birth interventions impact Oxtr regulation in the maternal brain.

Arginine-vasopressin (AVP) deficiency (AVP-D) is caused by hypothalamic-pituitary damage of vasopressinergic neurons leading to polyuria and polydipsia. Diagnostic tests for AVP-D are limited by low accuracy and/or tolerability. Kisspeptin (KP) stimulates AVP release in animals, but no study has investigated KP as a provocative test for AVP-D in humans. We investigated circulating AVP levels in response to intravenous (IV) KP in adults. We also explored sex differences in AVP response to KP. Twelve healthy adults (50% female) received an IV KP bolus. Serum AVP was measured pre- and 10, 20, 40, and 60 min post-KP. AVP levels were higher in males at all time points (p = .028) and did not change in response to KP. KP did not stimulate AVP, possibly due to dose, administration route, or cross-species differences in the AVP system. Our study does not support IV KP bolus of 0.24 nmol/kg as a provocative test for AVP-D. CLINICAL TRIAL REGISTRATION: Our study was registered on ClinicalTrials.gov (NCT00914823).

Oxytocin (OT) levels in blood plasma and OT receptor gene (OXTRm) methylation are two crucial pieces of the endogenous OT system that have been independently associated with social cognition. Empathy is a social-cognitive skill essential for understanding others' emotions and intentions, making it vital for everyday social interactions across the lifespan. Associations of plasma OT and OXTRm levels with empathy are currently not well understood among older adults, despite this period being marked by changes in both the endogenous OT system and empathy. Tying these previously separate lines of research together, this study examined the interplay of plasma OT and OXTRm on empathy in generally healthy older adults. Plasma OT levels were not directly related to empathy but for older adults with higher OXTRm levels higher plasma OT levels were associated with lower empathy scores. These results contribute to a growing literature on the intricate role of the endogenous OT system in social cognition in aging.

The purpose of this narrative review is to examine the hypothesis that two neuropeptides, vasopressin (VP) and oxytocin (OT) and their receptors have central roles in the behavioral and physiological consequences of psychedelic interventions. Transient consequences of psychedelics can include anxiety and in some cases sickness responses such as nausea and vomiting, which may involve VP and other components of the hypothalamic-pituitary-adrenal axis. Stressful experiences are often followed by a pulsatile release of OT. The effects of OT depend on interactions with VP and may be more apparent following stressful experiences including those associated with psychedelic drugs. Effects of both the VP-OT system and psychedelics also are mediated through interactions with the autonomic nervous system and the immune system, contributing to a process called "stress response hormesis." The hypotheses arising from a hormetic perspective could guide novel approaches to understanding dose- and time-dependent psychedelic functions and to the treatment of emotional and physical disorders.

The purpose of this article is to examine a previously unrecognized role for the vasopressin–oxytocin (VP-OT) system in mammalian “stress-response hormesis.” The current review adds hormesis to the long list of beneficial effects of OT. Hormesis, a biphasic adaptive response to low-level stressors, is introduced here to contextualize the dynamic roles of oxytocin and vasopressin. As with hormesis, the properties of the VP-OT system are context-, time-, and dose-sensitive. Here we suggest that one key to understanding hormesis is the fact that VP and OT and their receptors function as an integrated system. The VP-OT system is capable of changing and adapting to challenges over time, including challenges necessary for survival, reproduction and sociality. Prior research suggests that many beneficial effects of OT are most apparent only following stressful experiences, possibly reflecting interactions with VP, its receptors and other components of the hypothalamic–pituitary–adrenal axis. The release of OT is documented following various kinds of hormetic experiences such as birth, vigorous exercise, ischemic events and the ingestion of emetics, including psychedelics. The phasic or cyclic modulation of VP and related “stress” hormones, accompanied or followed by the release of OT, creates conditions that conform to the core principles of hormesis. This concept is reviewed here in the context of other hormones including corticotropin releasing hormone (CRH) and urocortin, as well as cytokines. In general, VP and classic “stress hormones” support an active response, helping to quickly mobilize body systems. OT interacts with all of these, and may subsequently re-establish homeostasis and precondition the organism to deal with future stressors. However, the individual history of an organism, including epigenetic modifications of classical stress hormones such as VP, can moderate the effects of OT. Oxytocin’s effects also help to explain the important role of sociality in mammalian resilience and longevity. A hormetic perspective, focusing on a dynamic VP-OT system, offers new insights into emotional and physical disorders, especially those associated with the management of chronic stress, and helps us to understand the healing power of social behavior and perceived safety.

CONTEXT:Oxytocin (OXT) and arginine-vasopressin (AVP) are structurally similar hypothalamic-pituitary peptides with broad physiologic actions including regulation of caloric intake and metabolism. While OXT is under investigation as an antiobesity therapeutic, there are no data on endogenous AVP levels in relation to eating behavior in humans. Further, the effects of exogenous OXT on AVP dynamics, which could affect safety of treatment given AVP effects on water balance, are not well understood. OBJECTIVE:This work aimed to define secretory dynamics of circulating AVP around a standardized meal and in response to 8 weeks (W) intranasal (IN) OXT vs placebo in adults with obesity. METHODS:Cross-sectional and longitudinal data were used from an 8-W randomized clinical trial at a tertiary academic center. Participants included 63 adults with obesity (56% women, age 33.7 ± 6.3 years) of whom 61 were randomly assigned 1:1 to 8-W IN OXT (24 IU) 4 times daily or placebo. Intervention included a standardized meal, IN OXT vs placebo. Main outcome measure was AVP levels before and 30, 60, and 120 minutes after a standardized meal at baseline, and W4, 6, and 8 after starting OXT or placebo. RESULTS:In response to food intake, AVP levels decreased at 60 minutes (adjusted mean ± SE = 68.55 ± 9.64 pg/mL) compared to fasting (80.99 ± 11.22 pg/mL; P = .022). AVP levels did not significantly change over the course of 8-W IN OXT treatment vs placebo (P ≥ .544). There was no effect of body mass index (P ≥ .615) or sex (P ≥ .498) on AVP levels. CONCLUSION:AVP levels decreased after food intake in adults with obesity, indicating a potential disruption in AVP signaling and possibly underlying obesity pathophysiology. Chronic IN OXT administration did not alter AVP levels, supporting safety of OXT-based therapeutics.

Background/Objectives. Medical and social care professionals (MSCPs) are disproportionately affected by chronic occupational stress, placing them at elevated risk for autonomic dysregulation, affective disorders, and burnout. Method. This preliminary study includes data obtained from two samples. The data protocols were approved by University of Florida's IRB (IRB202200233 approved 24 February 2023 and IRB202401217 approved on 2 October 2024) and registered at ClinicalTrials.gov (NCT05766852 and NCT06580119). With a total sample of 39 female MSCPs, we investigated the effects of the novel Somatic Psychoeducational Intervention (SPI), grounded in Polyvagal Theory, on autonomic reactivity, psychological distress symptoms, and salivary oxytocin levels. Participants engaged in a three- to four-week intervention integrating psychoeducation, interoceptive training, breathwork, and somatic movement. A subset was randomly assigned via a random number generator to allow for comparison of the intervention group (n = 8) to control group (n = 7). Results. Repeated measures ANOVA revealed increases in salivary oxytocin (ηp2 = 0.46) and reductions in autonomic reactivity (ηp2 = 0.24) and psychological distress symptoms (ηp2 ranging from 0.24 to 0.47). Benefits were sustained at one-month follow-up. Subset analyses focused on participants receiving the intervention at the same time found that only the participants in the intervention group improved with regard to autonomic reactivity and symptoms of anxiety and depression. Correlational analyses showed that changes in oxytocin and autonomic reactivity were associated with mindfulness improvements, which in turn predicted symptom reduction. Conclusions. These preliminary findings support SPI as a potentially scalable intervention with neurophysiological and psychological benefits. However, high attrition and small subgroup sizes necessitate cautious interpretation.

Oxytocin pathways are hypothesized to play important roles in human-animal interactions and may contribute to some benefits of these interspecific social relationships. We explored the effects of naturalistic interactions between children and dogs on oxytocin release in both species, as well as associations between methylation of the oxytocin receptor gene (OXTRm), social behavior, and oxytocin response in this context. Children (N = 55) participated in a within-subjects design involving a) interaction with their pet dog, b) interaction with an unfamiliar dog, and c) a nonsocial control condition (solitary play). We used immunoassays to measure salivary and urinary oxytocin in both the children and dogs, behavioral coding to characterize dog-child interactions, and bisulfite sequencing to quantify methylation of the oxytocin receptor gene (n = 32 children). Child salivary oxytocin decreased moderately across time in all conditions, but the extent of this effect varied between conditions, with greater oxytocin output during interactions with dogs than the control condition. In the pet dog condition, children’s salivary oxytocin response was positively associated with the duration of visual co-orientation between the child and dog. Child urinary oxytocin did not deviate substantially from baseline in any condition. Children with higher levels of OXTRm had greater oxytocin output during interactions with their pet dogs, but lower oxytocin output in the control condition, and engaged in lower levels of affectionate interaction with dogs across conditions. Children’s pet dogs exhibited increases in salivary oxytocin, but we observed the opposite pattern in the unfamiliar dog, who exhibited decreases in both urinary and salivary oxytocin on average. Collectively, our results support the hypothesis that oxytocin pathways may shape and respond to social interactions between children and dogs, highlighting an important role for companion animals in child development.

Exogenous oxytocin (OT) is widely used to induce or augment labor with little understanding of the impact on offspring development. In rodent models, including the prairie vole (Microtus ochrogaster), it has been shown that oxytocin administered to mothers can affect the nervous system of the offspring with long lasting behavioral effects especially on sociality. Here, we examined the hypothesis that perinatal oxytocin exposure could have epigenetic and transcriptomic consequences. Prairie voles were exposed to exogenous oxytocin, through injections given to the mother just prior to birth, and were studied at the time of weaning. The outcome of this study revealed increased epigenetic age in oxytocin-exposed animals compared to the saline-exposed group. Oxytocin exposure led to 900 differentially methylated CpG sites (annotated to 589 genes), and 2 CpG sites (2 genes) remained significantly different after correction for multiple comparisons. Differentially methylated CpG sites were enriched in genes known to be involved in regulation of gene expression and neurodevelopment. Using RNA-sequencing we also found 217 nominally differentially expressed genes (p<0.05) in nucleus accumbens, a brain region involved in reward circuitry and social behavior; after corrections for multiple comparisons 6 genes remained significantly differentially expressed. Finally, we found that maternal oxytocin administration led to widespread alternative splicing in the nucleus accumbens. These results indicate that oxytocin exposure during birth may have long lasting epigenetic consequences. A need for further investigation of how oxytocin administration impacts development and behavior throughout the lifespan is supported by these outcomes.

Neuroendocrine analyses of posttraumatic stress disorder (PTSD) have generally focused on hypothalamic-pituitary-adrenal (HPA) axis alterations. In the present analyses, we examine two additional neuroendocrine factors that have been previously implicated in biological stress responses: oxytocin (OT) and arginine vasopressin (AVP). Here we examined basal neuropeptide status in military veterans clinically diagnosed with PTSD (n = 29) and in two non- traumatized comparison groups with previous stress exposure (n = 11 SWAT trainees and n = 21 ultramarathon runners). PTSD patients showed low levels of plasma OT and high levels of AVP. The ratio of AVP/OT robustly related to PTSD status, and emerged as a statistically plausible mediator of relationships between the number of personal traumatic experiences and subsequent PTSD symptom burden. Over the course of behavioral therapy for PTSD, measures of OT showed a significant but modest normalization. Plasma cortisol levels were not statistically different among the three groups. This study suggests that AVP/OT ratios may represent a neuroendocrine predictor of severe PTSD, as well as a potential treatment response biomarker.

This study aimed to increase our understanding of cardiac activity abnormalities in Prader-Willi Syndrome (PWS) and the relationship between cardiac activity, PWS behaviours thought to be associated with cardiac vagal tone and endogenous oxytocin and vasopressin levels. We compared cardiac activity (respiratory sinus arrhythmia (RSA), low-frequency heart rate variability (LF-HRV), heart period) in 30 adolescents and adults with PWS to 30 typically developing age-matched controls. RSA, LF-HRV, and heart period were lower in individuals with PWS than in the control group. In the control group, RSA was higher for females than males. However, for those with PWS, there was no difference between the sexes. Individuals with the mUPD genetic subtype had lower RSA and LF-HRV than participants with the PWS deletion subtype and compared to typically developing controls, no difference was found between the latter two groups. Heart period was also lower for those with mUPD compared to controls. Higher RSA reduced the odds of having temper outbursts and skin-picking. RSA was lower in those with PWS and psychosis compared to those with PWS without psychosis. Finally, we found RSA correlated with vasopressin for those with mUPD but not deletion. There was no relationship between RSA and oxytocin plasma or saliva levels. Our findings suggest autonomic dysfunction in PWS that is more marked in mUPD than deletion and potentially due to greater loss of parasympathetic activity in mUPD.