Oxytocin Response Research Articles

Effects of human-animal interaction on salivary and urinary oxytocin in children and dogs

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.

Changes in salivary oxytocin in response to biologically-relevant events in farm animals: method optimization and usefulness as a biomarker.

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.

FRI003 Oxytocin Response To Feeding Predicts Reward-driven Calorie Consumption In Adults With Obesity

Abstract Disclosure: R. Boutin: None. M. Wronski: None. A. Aulinas Maso: None. M. Muhammed: None. F. Galbiati: None. L. Kerem: None. S. Carter: None. H. Nazarloo: None. J.M. Davis: None. K. Holman: None. J. Gydus: None. S. Smith: None. E. Asanza: None. F. Plessow: None. E.A. Lawson: Consulting Fee; Self; OXT Therapeutics. Stock Owner; Self; OXT Therapeutics. Objectives: Oxytocin (OXT) is a hypothalamic peptide hormone that reduces reward-related food intake and is under investigation as a potential weight loss therapy. Activation of OXT neurons in appetite pathways results in suppression of posterior pituitary release of OXT to the circulation, such that peripheral OXT levels (in response to feeding) may reflect the opposite of central OXT activity. While a relationship between peripheral OXT response to feeding and appetite has been reported in healthy females, there are no data related to OXT levels and appetite or eating behavior in individuals with obesity. We hypothesized that in individuals with obesity, higher OXT levels in response to feeding would be associated with greater reward-driven food intake assessed during a Cookie Taste Test. Methods: In a cross-sectional study of 53 adults with obesity (56% females; age [mean±SD] 33.7±6.2 years; BMI 36.9±4.9 kg/m2), participants presented after an overnight fast and were provided with a standard 400 kcal mixed meal. We sampled blood before and 30, 60 and 120 minutes after the meal for OXT levels and calculated area under the curve (AUC) as an integrated measure of OXT response to feeding. After receiving a subsequent snack, subjects ate as many cookies as needed to rate the cookies on various characteristics (i.e. sweetness, texture, delectability). We logarithmically transformed non-normal data to achieve a normalized distribution and used Pearson correlation to evaluate the relationship between OXT AUC and number of calories eaten during the Cookie Taste Test (behavioral marker of reward-related eating). Results: OXT AUC in response to a standardized meal predicted subsequent calories consumed at the Cookie Taste Test (R=0.30, p=0.036), such that those with higher OXT levels consumed more calories. Conclusions: Consistent with our hypothesis, peripheral OXT response to a standardized meal predicted subsequent reward-driven caloric intake in adults with obesity. These data suggest that endogenous OXT is involved in regulation of hedonic eating and supports targeting OXT pathways in the treatment of obesity. Presentation: Friday, June 16, 2023

Oxytocin response to food intake in avoidant/restrictive food intake disorder.

To investigate the response of anorexigenic oxytocin to food intake among adolescents and young adults with avoidant/restrictive food intake disorder (ARFID), a restrictive eating disorder characterized by lack of interest in food or eating, sensory sensitivity to food, and/or fear of aversive consequences of eating, compared with healthy controls (HC). Cross-sectional. A total of 109 participants (54 with ARFID spectrum and 55 HC) were instructed to eat a ∼400-kcal standardized mixed meal. We sampled serum oxytocin at fasting and at 30-, 60-, and 120-min postmeal. We tested the hypothesis that ARFID would show higher mean oxytocin levels across time points compared with HC using a mixed model ANOVA. We then used multivariate regression analysis to identify the impact of clinical characteristics (sex, age, and body mass index [BMI] percentile) on oxytocin levels in individuals with ARFID. Participants with ARFID exhibited greater mean oxytocin levels at all time points compared with HC, and these differences remained significant even after controlling for sex and BMI percentile (P = .004). Clinical variables (sex, age, and BMI percentile) did not show any impact on fasting and postprandial oxytocin levels among individuals with ARFID. Consistently high oxytocin levels might be involved in low appetite and sensory aversions to food, contributing to food avoidance in individuals with ARFID.

Therapists' oxytocin response mediates the association between patients' negative emotions and psychotherapy outcomes

BackgroundExisting literature suggests that patients' experiences of emotions, especially negative emotions, predict outcomes in psychotherapies for major depressive disorder. However, the specific mechanisms underlying this effect remain unclear. Based on studies pointing to the role of oxytocin (OT) in attachment relationships, we proposed and tested a mediation model where the therapists' hormonal responses, as represented by increases in their OT levels, mediates the association between negative emotions and symptomatic change. MethodOT saliva samples (pre- and post-session, N = 435) were collected on a fixed schedule over 16 sessions from the therapists of 62 patients receiving psychotherapy for major depression. The Hamilton Rating Scale for Depression was administered to the patients before the sessions, and the patients reported their in-session emotions after the sessions. ResultsThe findings support the proposed within-person mediation model: (a) higher levels of negative emotions in patients predicted greater increases in therapist OT levels pre- to post-session throughout treatment; (b) greater OT levels in therapists, in turn, predicted reduction in patients' depressive symptoms on the subsequent assessment; and (c) the therapists' OT levels significantly mediated the association between patients' negative emotions and reduction in their depressive symptoms. LimitationsThis design precluded establishing a time sequence between patients' negative emotions and therapists' OT; thus, causality could not be inferred. ConclusionThese findings point to a possible biological mechanism underlying the effects of patients' experiences of negative emotions on treatment outcomes. The findings suggest that therapists' OT responses could potentially serve as a biomarker of an effective therapeutic processes.

Effect of Neurosteroids on Basal and Stress-Induced Oxytocin Secretion in Luteal-Phase and Pregnant Sheep.

Oxytocin (OT) is a neuropeptide synthesized in the hypothalamic nuclei that modulates both behavioral and reproductive functions, associated with the increased neurosteroid synthesis in the brain. Therefore, the present study tested the hypothesis that manipulation of central neurosteroid levels could affect oxytocin synthesis and release in non-pregnant and pregnant sheep under both basal and stressful conditions. In Experiment 1, luteal-phase sheep were subjected to a series of intracerebroventricular (icv.) infusions of allopregnanolone (AL, 4 × 15 μg/60 μL/30 min) for 3 days. In Experiment 2, pregnant animals (4th month) received a series of infusions of the neurosteroid synthesis blocker, finasteride (4 × 25 μg/60 μL/30 min), conducted for 3 days. In non-pregnant sheep AL alone was shown to differentially modulate OT synthesis in basal conditions, and strongly inhibit OT response to stress (p < 0.001). In contrast, in pregnant animals, basal and stress-induced OT secretion was significantly (p < 0.001) increased during finasteride infusion compared to controls. In conclusion, we showed that neurosteroids were involved in the control of OT secretion in sheep, particularly under stress and pregnancy conditions and are part of an adaptive mechanism which is responsible for protecting and maintaining pregnancy in harmful situations.

Oxytocin in response to MDMA provocation test in patients with arginine vasopressin deficiency (central diabetes insipidus): a single-centre, case-control study with nested, randomised, double-blind, placebo-controlled crossover trial

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.

Human endogenous oxytocin and its neural correlates show adaptive responses to social touch based on recent social context.

Both oxytocin (OT) and touch are key mediators of social attachment. In rodents, tactile stimulation elicits the endogenous release of OT, potentially facilitating attachment and other forms of prosocial behavior, yet the relationship between endogenous OT and neural modulation remains unexplored in humans. Using a serial sampling of plasma hormone levels during functional neuroimaging across two successive social interactions, we show that contextual circumstances of social touch influence not only current hormonal and brain responses but also later responses. Namely, touch from a male to his female romantic partner enhanced her subsequent OT release for touch from an unfamiliar stranger, yet females' OT responses to partner touch were dampened following stranger touch. Hypothalamus and dorsal raphe activation reflected plasma OT changes during the initial social interaction. In the subsequent interaction, precuneus and parietal-temporal cortex pathways tracked time- and context-dependent variables in an OT-dependent manner. This OT-dependent cortical modulation included a region of the medial prefrontal cortex that also covaried with plasma cortisol, suggesting an influence on stress responses. These findings demonstrate that modulation between hormones and the brain during human social interactions can flexibly adapt to features of social context over time.

Adolescents' Hormonal Responses to Social Stress and Associations with Adolescent Social Anxiety and Maternal Comfort: A Preliminary Study.

Both social support and social stress can impact adolescent physiology including hormonal responses during the sensitive transition to adolescence. Social support from parents continues to play an important role in socioemotional development during adolescence. Sources of social support and stress may be particularly impactful for adolescents with social anxiety symptoms. The goal of the current study was to examine whether adolescent social anxiety symptoms and maternal comfort moderated adolescents' hormonal response to social stress and support. We evaluated 47 emotionally healthy 11- to 14-year-old adolescents' cortisol and oxytocin reactivity to social stress and support using a modified version of the Trier Social Stress Test for Adolescents that included a maternal comfort paradigm. Findings demonstrated that adolescents showed significant increases in cortisol and significant decreases in oxytocin following the social stress task. Subsequently, we found that adolescents showed significant decreases in cortisol and increases in oxytocin following the maternal comfort paradigm. Adolescents with greater social anxiety symptoms showed higher levels of cortisol at baseline but greater declines in cortisol response following maternal social support. Social anxiety symptoms were unrelated to oxytocin response to social stress or support. Our findings provide further evidence that mothers play a key role in adolescent regulation of physiological response, particularly if the stressor is consistent with adolescents' anxiety. More specifically, our findings suggest that adolescents with higher social anxiety symptoms show greater sensitivity to maternal social support following social stressors. Encouraging parents to continue to serve as a supportive presence during adolescent distress may be helpful for promoting stress recovery during the vulnerable transition to adolescence.

Release of Oxytocin and Cortisol Is Associated With Neurobehavioral Patterns in Premature Infants

ObjectiveTo examine relationships among salivary oxytocin and cortisol levels in parents and preterm infants and neurobehavioral functioning in preterm infants after skin-to-skin contact. DesignA secondary analysis of a randomized crossover study. SettingNICU. ParticipantsTwenty-eight stable premature infants and their mothers and fathers. MethodsParticipating infants contributed 108 saliva samples that we collected 45 minutes after skin-to-skin contact and tested for oxytocin and cortisol. We randomized data collection by whether the infant was held first by the mother or by the father. We conducted linear regression to test if summary scores on the NICU Network Neurobehavioral Scale were associated with salivary oxytocin and cortisol levels. ResultsWe found a significant negative relationship between infant oxytocin levels and the Stress scores (b = –0.07, p < .01) and the Excitability scores (b = –1.12, p = .04) among infants held skin-to-skin with their mothers. We found a significant positive relationship between infant oxytocin levels and the Self-Regulatory scores (b = 0.38, p = .05) among infants held skin-to-skin with their mothers. We found a significant positive relationship between infant cortisol level and the Stress scores (b = 0.05, p = .04), Excitability scores (b = 1.06, p = 0.05), and Asymmetrical Reflexes scores (b = 1.21, p = .03) among infants held skin-to-skin with their mothers. We only found a negative significant relationship between infant cortisol levels and the Stress scores (b = –0.03, p = .04) among infants held skin-to-skin with their fathers. ConclusionWe found that oxytocin is an important biomarker that may improve infant neurobehavioral functioning. The data showed a difference in oxytocin responses after skin-to-skin contact with mothers compared to fathers.

Oxytocin receptor single nucleotide polymorphism predicts atony-related postpartum hemorrhage

BackgroundPostpartum hemorrhage remains a key contributor to overall maternal morbidity in the United States. Current clinical assessment methods used to predict postpartum hemorrhage are unable to prospectively identify about 40% of hemorrhage cases. Oxytocin is a first-line pharmaceutical for preventing and treating postpartum hemorrhage, which acts through oxytocin receptors on uterine myocytes. Existing research indicates that oxytocin function is subject to variation, influenced in part by differences in the DNA sequence within the oxytocin receptor gene. One variant, rs53576, has been shown to be associated with variable responses to exogenous oxytocin when administered during psychological research studies. How this variant may influence myometrial oxytocin response in the setting of third stage labor has not been studied. We tested for differences in the frequency of the oxytocin receptor genotype at rs53576 in relationship to the severity of blood loss among a sample of individuals who experienced vaginal birth.MethodsA case–control prospective design was used to enroll 119 postpartum participants who underwent vaginal birth who were at least 37 weeks of gestation. Cases were defined by either a 1000 mL or greater blood loss or instances of heavier bleeding where parturients were given additional uterotonic treatment due to uterine atony. Controls were matched to cases on primiparity and labor induction status. Genotype was measured from a maternal blood sample obtained during the 2nd postpartum month from 95 participants. Statistical analysis included bivariate tests and generalized linear and Poisson regression modeling.ResultsThe distribution of the genotype across the sample of 95 participants was 40% GG (n = 38), 50.5% AG (n = 48) and 9.5% AA (n = 9). Blood loss of 1000 mL or greater occurred at a rate of 7.9% for GG, 12.5% for AG and 55.6% for AA participants (p = 0.005). Multivariable models demonstrated A-carriers (versus GG) had 275.2 mL higher blood loss (95% CI 96.9–453.4, p < 0.01) controlling for parity, intrapartum oxytocin, self-reported ancestry, active management of third stage or genital tract lacerations. Furthermore, A-carrier individuals had a 79% higher risk for needing at least one second-line treatment (RR = 1.79, 95% CI = 1.08–2.95) controlling for covariates. Interaction models revealed that A-carriers who required no oxytocin for labor stimulation experienced 371.4 mL greater blood loss (95% CI 196.6–546.2 mL).ConclusionsWe provide evidence of a risk allele in the oxytocin receptor gene that may be involved in the development of postpartum hemorrhage among participants undergoing vaginal birth, particularly among those with fewer risk factors. The findings, if reproducible, could be useful in studying pharmacogenomic strategies for predicting, preventing or treating postpartum hemorrhage.

PMON58 Endogenous Oxytocin Response to Food Intake in Avoidant/Restrictive Food Intake Disorder Compared to Healthy Controls

Abstract Context In healthy individuals, serum levels of oxytocin, an anxiolytic hypothalamic-pituitary hormone involved in appetite regulation and response to stress, decrease post-prandially. Oxytocin response to a meal in Avoidant/Restrictive Food Intake Disorder (ARFID), a psychiatric disorder characterized by restrictive eating driven by lack of interest in food, sensory sensitivity, and/or fear of aversive consequences and associated with comorbid anxiety, is unknown. We compared the pattern of postprandial oxytocin levels in individuals with ARFID to healthy controls (HC). We hypothesized that overall oxytocin levels would be higher in ARFID vs HC as an adaptive response to stress. Methods 109 participants (55 with ARFID and 54 HC) were instructed to eat a ∼400-kcal standardized mixed meal. Serum oxytocin was sampled fasting and 30, 60, and 120 minutes post-meal. Anxiety was assessed using the trait scale of the State-Trait Anxiety Inventory (STAI). All data are presented as mean±SEM. Multivariate regression analysis was used to control for confounding variables. Results Mean age did not differ across groups (ARFID: 16.9±0.5 and HC: 17.8±0.5 years, p=0.197). Mean body mass index percentile (BMIp) was lower in ARFID compared to HC (37.3±4.9 vs 53.7±2.9, respectively, p=0.004). Sex distribution differed between groups [ARFID: 27 (50%) males, 27 (50%) females vs HC: 15 (27%) males and 40 (73%) females, p=0.019)]. Anxiety symptoms were higher in ARFID compared to HC (38.5±1.8 vs 30.3±1.0, respectively, p=0.0007). By study design, quantity of food consumed did not differ across groups (p=0.238), however, ARFID participants ate a higher % of fat than HC (22.8±0.5 vs. 21.6±0.4, p=0.027). Mean oxytocin levels were higher in ARFID compared to HC at all time points (fasting: 1487±94 vs 1268±60 pg/mL, p=0.049; 30 min: 1477±86 vs 1202±48 pg/mL, p=0.006; 60 min: 1473±89 vs 1214±52 pg/mL, p=0.015; 120 min: 1470±102 vs 1253±50 pg/mL, respectively, p=0.056), and AUC (p=0.023). While mean oxytocin decreased postprandially as expected in HC (30 min p=0.028 and 60 min p=0.072), there was no postprandial change in oxytocin levels in ARFID from fasting to any postprandial timepoint (p≥0.746). Multivariate regression analysis revealed that both ARFID group (β=41,213, η2p = 0.084, p=0.004) and BMIp (β=779, η2p = 0.129, p&amp;lt;0.001) accounted for higher oxytocin levels irrespective of sex, fat intake and anxiety levels (R2=0.192). Conclusions This is the first study to determine the pattern of endogenous oxytocin secretion in response to a meal in a large group of individuals with ARFID. Mean oxytocin levels fasting and in response to a meal are higher in ARFID compared to HC, irrespective of sex, quantity of fat consumed, and anxiety symptoms. Unlike in healthy individuals, oxytocin levels in ARFID do not decrease in response to eating. These data suggest that dysregulated oxytocin secretion may play a role in the pathophysiology of ARFID. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Endogenous oxytocin levels in extracted saliva elevates during breastfeeding correlated with lower postpartum anxiety in primiparous mothers

BackgroundBreastfeeding in the early postpartum period is expected to have mental benefits for mothers; however, the underlying psychobiological mechanisms remain unclear. Previously, we hypothesized that the release of oxytocin in response to the suckling stimuli during breastfeeding would mediate a calming effect on primiparous mothers, and we examined salivary oxytocin measurements in primiparous mothers at postpartum day 4 using saliva samples without extraction, which was erroneous. Thus, further confirmation of this hypothesis with a precise methodology was needed.MethodsWe collected saliva samples at three time points (baseline, feeding, and post-feeding) to measure oxytocin in 24 primiparous mothers on postpartum day 2 (PD2) and 4 (PD4) across the breastfeeding cycle. Salivary oxytocin levels using both extracted and unextracted methods were measured and compared to determine the qualitative differences. State and trait anxiety and clinical demographics were evaluated to determine their association with oxytocin changes.ResultsBreastfeeding elevated salivary oxytocin levels; however, it was not detected to a significant increase in the extraction method at PD4. We found a weak but significant positive correlation between changes in extracted and unextracted oxytocin levels during breastfeeding (feeding minus baseline); there were no other significant positive correlations. Therefore, we used the extracted measurement index for subsequent analysis. We showed that the greater the increase in oxytocin during breastfeeding, the lower the state anxiety, but not trait anxiety. Mothers who exclusively breastfed at the 1-month follow-up tended to be associated with slightly higher oxytocin change at PD2 than those who did not.ConclusionsBreastfeeding in early postpartum days could be accompanied by the frequent release of oxytocin and lower state anxiety, potentially contributing to exclusive breastfeeding.

Oxytocin moderates corticolimbic social stress reactivity in cocaine use disorder and healthy controls

Social stress can contribute to the development of substance use disorders (SUDs) and increase the likelihood of relapse. Oxytocin (OT) is a potential pharmacotherapy that may buffer the effects of social stress on arousal and reward neurocircuitry. However, more research is needed to understand how OT moderates the brain’s response to social stress in SUDs. The present study examined the effect of intransasal OT (24 IU) versus placebo (PBO) on corticolimbic functional connectivity associated with acute social stress in individuals with cocaine use disorder (CUD; n = 67) and healthy controls (HC; n = 52). Psychophysiological interaction modeling used the left and right amygdala as seed regions with the left and right orbitofrontal and anterior cingulate cortex as a priori regions of interest. Moderators of the OT response included childhood trauma history and biological sex, which were examined in independent analyses. The main finding was that OT normalized corticolimbic connectivity (left amygdala-orbitofrontal and left amygdala-anterior cingulate) as a function of childhood trauma such that connectivity was different between trauma-present and trauma-absent groups on PBO, but not between trauma groups on OT. Effects of OT on corticolimbic connectivity were not different as a function of diagnosis (CUD vs HC) or sex. However, OT reduced subjective anxiety during social stress for CUD participants who reported childhood trauma compared to PBO and normalized craving response as a function of sex in CUD. The present findings add to some prior findings of normalizing effects of OT on corticolimbic circuitry in individuals with trauma histories and provide some initial support that OT can normalize subjective anxiety and craving in CUD.

A randomized controlled trial examining the effects of intranasal oxytocin on alcohol craving and intimate partner aggression among couples

BackgroundWhile alcohol use disorder (AUD) is a well-established risk factor for intimate partner aggression (IPA), effective treatments for co-occurring AUD and IPA (AUD/IPA) are lacking. Oxytocin is one promising pharmacological candidate for AUD/IPA given its potential to modulate social behavior and attenuate alcohol use. However, emerging data suggests that oxytocin's prosocial effects are inconsistent, and a small number of studies have also found that oxytocin might have the potential to be aggressogenic. No studies have directly examined the impact of oxytocin on alcohol- or IPA-related outcomes in a dyadic context. MethodsThe goal of this double-blind, randomized, and placebo-controlled trial was to examine the effects of a single dose of intranasal oxytocin (40 international units) on cue-induced alcohol craving, subjective aggression, laboratory task-based IPA, and cortisol reactivity in a sample of 100 couples (N = 200 individuals) with AUD and physical IPA in their current relationship. ResultsThere were no statistically significant differences between the oxytocin and placebo conditions for any of the primary outcomes. ConclusionsFindings suggest that a single dose of intranasal oxytocin was not efficacious in mitigating alcohol craving or aggression in this sample. Although hypotheses were not supported, the findings provide important evidence that oxytocin was not aggressogenic in this high-risk sample. Future research investigating dispositional and contextual moderators of oxytocin response in addition to the therapeutic effects of more intensive oxytocin dosing or administration strategies on alcohol craving and aggression is warranted.

Pharmacological chaperones for the oxytocin receptor increase oxytocin responsiveness in myometrial cells

Oxytocin is a potent uterotonic agent administered to nearly all patients during childbirth in the United States. Inadequate oxytocin response can necessitate Cesarean delivery or lead to uterine atony and postpartum hemorrhage. Thus, it may be clinically useful to identify patients at risk for poor oxytocin response and develop strategies to sensitize the uterus to oxytocin. Previously, we showed that the V281M variant in the oxytocin receptor (OXTR) gene impairs OXTR trafficking to the cell surface, leading to a decreased oxytocin response in cells. Here, we sought to identify pharmacological chaperones that increased oxytocin response in cells expressing WT or V281M OXTR. We screened nine small-molecule agonists and antagonists of the oxytocin/vasopressin receptor family and identified two, SR49059 and L371,257, that restored both OXTR trafficking and oxytocin response in HEK293T cells transfected with V281M OXTR. In hTERT-immortalized human myometrial cells, which endogenously express WT OXTR, treatment with SR49059 and L371,257 increased the amount of OXTR on the cell surface by two- to fourfold. Furthermore, SR49059 and L371,257 increased the endogenous oxytocin response in hTERT-immortalized human myometrial cells by 35% and induced robust oxytocin responses in primary myometrial cells obtained from patients at the time of Cesarean section. If future studies demonstrate that these pharmacological chaperones or related compounds function similarly in vivo, we propose that they could potentially be used to enhance clinical response to oxytocin.

Oxytocin: a new target for neuroprotection?

Every year, 30 million infants worldwide are delivered after intra-uterine growth restriction (IUGR) and 15 million are born preterm. These two conditions are the leading causes of ante-/perinatal stress and brain injury responsible for neurocognitive and behavioral disorders affecting more than 9 million children each year. Most pharmacological candidates to prevent perinatal brain damage have failed to demonstrate substantial benefits. In contrast, environment enrichment based on developmental care, skin-to-skin contact and vocal/music exposure appear to exert positive effects on brain structure and function. However, mechanisms underlying these effects remain unknown. There is strong evidence that an adverse environment during pregnancy and the neonatal period can influence hormonal responses of the newborn with long-lasting neurobehavioral consequences in infancy and adulthood. In particular, excessive cortisol release in response to perinatal stress associated with prematurity or IUGR is recognized to induce brain-programming effects and neuroinflammation, a key predictor of subsequent neurological impairments. These deleterious effects are known to be balanced by oxytocin (OT), a neuropeptide released by the hypothalamus, which plays a role during the perinatal period and in social behavior. In addition, preclinical studies suggest that OT is able to regulate the central inflammatory response to injury in the adult brain. Using a rodent model of IUGR associated with developing white matter damage, we recently reported that carbetocin, a brain permeable OT receptor (OTR) agonist, induced a significant reduction of activated microglia, the primary immune cells of the brain. Moreover, this reduced microglia reactivity was associated with long-term neuroprotection. These findings make OT a promising candidate for neonatal neuroprotection through neuroinflammation regulation. However, the mechanisms linking endogenous OT and central inflammation response to injury have not yet been established. Further studies are needed to assess the protective role of OT in the developing brain through modulation of microglial activation, a key feature of brain injury observed in infants born preterm or growth-restricted. They are expected to have several impacts in the near future not only for improving knowledge of microglial cell physiology and reactivity during brain development, but also to design clinical trials testing interventions associated with endogenous OT release as a relevant strategy to alleviate neuroinflammation in neonates.

The contributions of maternal oxytocin and maternal sensitivity to infant attachment security

ABSTRACT This study investigated links between maternal postnatal oxytocin, maternal sensitivity, and infant attachment security. At 3-months postpartum, participants (n=88) took part in a structured parent-infant interaction. Maternal oxytocin levels were assessed via blood, before and after the interaction. At 12-months postpartum, mother-child dyads completed the Strange Situation Procedure. Neither baseline oxytocin, oxytocin response, or maternal sensitivity were identified as significant independent predictors of infant attachment security or organisation. However, an interaction effect was identified, with higher maternal sensitivity being associated with secure infant attachment for mothers who showed an increase in oxytocin during parent–child interaction. Results indicate that maternal sensitivity, when accompanied by an increase in maternal oxytocin during parent–child interaction, is associated with the establishment of a positive early parent–child attachment relationship. This adds to the growing body of evidence highlighting maternal oxytocin response as a key adaptive process in the postpartum period.

Longitudinal tracking of human plasma oxytocin suggests complex responses to moral elevation

Positive social experiences may induce oxytocin release. However, previous studies of moral elevation have generally utilized cross-sectional and simple modeling approaches to establish the relationship between oxytocin and emotional stimuli. Utilizing a cohort of 30 non-lactating women (aged 23.6 ± 5.7 years), we tested whether exposure to a video identified as capable of eliciting moral elevation could change plasma oxytocin levels. Uniquely, we utilized a high-frequency longitudinal sampling approach and multilevel growth curve modeling with landmark registration to test physiological responses. The moral elevation stimulus, versus a control video, elicited significantly greater reports of being “touched/inspired” and “happy/joyful”. However, the measured plasma oxytocin response was found to be markedly heterogeneous. While the moral elevation stimulus elicited increased plasma oxytocin as expected, this increase was only modestly larger than that seen following the control video. This increase was also only present in some individuals. We found no relationship between plasma oxytocin and self-report responses to the stimulus. From these data, we argue that future studies of the relationship between oxytocin and emotion need to anticipate heterogeneous responses and thus incorporate comprehensive individual psychological data; these should include evidence-based variables known to be associated with oxytocin such as a history of trauma, and the individual’s psychological and emotional state at the time of testing. Given the complexity of physiological oxytocin release, such studies also need to incorporate frequent biological sampling to properly examine the dynamics of hormonal release and response.

Exploring women's oxytocin responses to interactions with their pet cats.

BackgroundExtensive research has evaluated the involvement of the neuropeptide oxytocin (OT) in human social behaviors, including parent-infant relationships. Studies have investigated OT’s connection to human attachment to nonhuman animals, with the majority of the literature focusing on domestic dogs (Canis lupis familiaris). Utilizing what is known about OT and its role in maternal-infant and human-dog bonding, we apply these frameworks to the study of human-domestic cat (Felis catus) interactions.MethodsWe investigated changes in salivary OT levels in 30 U.S. women of reproductive age before and after two conditions: reading a book (control) and interacting with their pet cat. Participant and cat behavioral patterns during the cat interaction condition were also quantified to determine if differences in women’s OT concentrations were associated with specific human and cat behaviors.ResultsOur results revealed no changes in women’s OT levels during the cat interaction, relative to the control condition, and pre-cat interaction OT levels. However, differences in women’s OT concentrations were correlated with some human-cat interactions (e.g., positively with petting cat and cat approach initiation, negatively with cat agonistic behavior) but not all observed behaviors (e.g., use of gentle or baby voice) coded during human-cat interactions.DiscussionThis study is the first to explore women’s OT in response to interactions with their pet cat and has identified distinct human and cat behaviors that influence OT release in humans.