Oxytocin Nasal Spray Research Articles

Applying a drift diffusion model to test the effect of oxytocin on attentional biases in body dysmorphic disorder

Individuals with body dysmorphic disorder (BDD) display selective attentional biases to threat. Oxytocin is an endogenous neuropeptide proposed to modulate attentional salience in social contexts. We conducted a secondary analysis applying drift diffusion modeling (DDM) to test whether individuals with BDD would display an attentional bias to threat, and whether oxytocin would modulate this bias. Eighteen participants with BDD and 15 healthy controls received an oxytocin or placebo nasal spray during two study visits, in randomized order, and completed a modified spatial cueing paradigm. DDM successfully parsed distinct task components demonstrating a selective attentional bias to disgust versus neutral faces in BDD compared to controls in the placebo condition, and a main effect of oxytocin on exacerbating this bias across participants. There were no effects using mean reaction time measures. DDM may reveal insights about attentional biases by utilizing trial-wise information. Oxytocin may exacerbate attentional biases to threat in BDD. General scientific summaryDrift diffusion modeling successfully parsed distinct components of a modified spatial cueing task that assessed attentional biases in those with body dysmorphic disorder (BDD) and healthy controls that were missed in conventional analyses using mean reaction time measures. Individuals with BDD displayed an attentional preference for disgust versus neutral faces in the placebo condition, and oxytocin exacerbated this attentional bias.

Effect of intranasal oxytocin combination therapy with applied behavior analysis on social impairments in pediatric’s children with autism spectrum disorder

BackgroundThe use of oxytocin as a therapy to treat social deficiencies in autism spectrum disorders (ASD) is gaining popularity. This study aimed to determine oxytocin nasal spray’s effect in combination with applied behavior analysis (ABA) method in improving social impairments in pediatrics with ASD.ResultsOur study’s main findings have revealed that intervention with INT-OXT compared to NS effectively reduced the ASD index and stereotyped behaviors on the GARS-2 scale (p < 0.05), in addition to teacher and parent’s SDQ mean score (p < 0.001). Also, during the follow-up time, the intervention with INT-OXT in ASD index, stereotyped behaviors, communication, social interaction, and parent and teacher mean SDQ scores were statically significant (p < 0.001).ConclusionsIn pediatrics with autism aged between 4 and 17 years, a 6-week course of INT-OXT combination therapy with ABA improved GARS-2 and teacher and parent SDQ scores compared to NS.

540. A Precision Medicine Approach to Oxytocin Nasal Spray in Autism: A Randomized Controlled Trial

540. A Precision Medicine Approach to Oxytocin Nasal Spray in Autism: A Randomized Controlled Trial

The effect and mechanism of oxytocin nasal spray on postpartum depression in primipara

The effect and mechanism of oxytocin nasal spray on postpartum depression in primipara

The effect of oxytocin nasal spray on social interaction in young children with autism: a randomized clinical trial

Early supports to enhance social development in children with autism are widely promoted. While oxytocin has a crucial role in mammalian social development, its potential role as a medication to enhance social development in humans remains unclear. We investigated the efficacy, tolerability, and safety of intranasal oxytocin in young children with autism using a double-blind, randomized, placebo-controlled, clinical trial, following a placebo lead-in phase. A total of 87 children (aged between 3 and 12 years) with autism received 16 International Units (IU) of oxytocin (n = 45) or placebo (n = 42) nasal spray, morning and night (32 IU per day) for twelve weeks, following a 3-week placebo lead-in phase. Overall, there was no effect of oxytocin treatment over time on the caregiver-rated Social Responsiveness Scale (SRS-2) (p = 0.686). However, a significant interaction with age (p = 0.028) showed that for younger children, aged 3–5 years, there was some indication of a treatment effect. Younger children who received oxytocin showed improvement on caregiver-rated social responsiveness ( SRS-2). There was no other evidence of benefit in the sample as a whole, or in the younger age group, on the clinician-rated Clinical Global Improvement Scale (CGI-S), or any secondary measure. Importantly, placebo effects in the lead-in phase were evident and there was support for washout of the placebo response in the randomised phase. Oxytocin was well tolerated, with more adverse side effects reported in the placebo group. This study suggests the need for further clinical trials to test the benefits of oxytocin treatment in younger populations with autism.Trial registration www.anzctr.org.au (ACTRN12617000441314).

Placebo induced expectations of mood enhancement generate a positivity effect in emotional processing

A perceptual bias towards negative emotions is a consistent finding in mood disorders and a major target of therapeutic interventions. Placebo responses in antidepressant treatment are substantial, but it is unclear whether and how underlying expectancy effects can modulate response biases to emotional inputs. In a first attempt to approach this question, we investigated how placebo induced expectation can shape the perception of specific emotional stimuli in healthy individuals. In a controlled cross-over design, positive treatment expectations were induced by verbal instructions and a hidden training manipulation combined with an alleged oxytocin nasal spray before participants performed an emotion classification task on happy and fearful facial expressions with varying intensity. Analyses of response criterion and discrimination ability as derived from emotion-specific psychometric functions demonstrate that expectation specifically lowered participants’ threshold for identifying happy emotions in general, while they became less sensitive to subtle differences in emotional expressions. These indications of a positivity bias were directly correlated with participants’ treatment expectations as well as subjective experiences of treatment effects and went along with a significant mood enhancement. Our findings show that expectations can induce a perceptual positivity effect in healthy individuals which is probably modulated by top-down emotion regulation and which may be able to improve mood state. Clinical implications of these promising results now need to be explored in studies of expectation manipulation in patients with mood disorders.

Nipple Aspirate Fluid at a Glance.

Simple SummaryNipple aspirate fluid (NAF) is a promising source of markers for detection of breast cancer. NAF can be acquired via the nipple by aspiration using a suction device, which is well tolerated by women. Future possible applications of biomarkers for breast cancer derived from NAF could be (1) as a detection tool to identify the initiation of the cancer development process, (2) as an additional tool next to imaging (mammography and breast magnetic resonance imaging) or (3) as a replacement tool for when imaging is not advisable for women, such as during pregnancy and breastfeeding. With this paper, we present a narrative review and perspectives of NAF research at a glance.Nipple aspirate fluid (NAF) is an intraductal mammary fluid that, because of its close proximity to and origin from the tissue from which breast cancer originates, is a promising source of biomarkers for early breast cancer detection. NAF can be non-invasively acquired via the nipple by aspiration using a suction device; using oxytocin nasal spray helps increase yield and tolerability. The aspiration procedure is generally experienced as more tolerable than the currently used breast imaging techniques mammography and breast magnetic resonance imaging. Future applications of NAF-derived biomarkers include their use as a tool in the detection of breast carcinogenesis at its earliest stage (before a tumor mass can be seen by imaging), or as a supporting diagnostic tool for imaging, such as when imaging is less reliable (to rule out false positives from imaging) or when imaging is not advisable (such as during pregnancy and breastfeeding). Ongoing clinical studies using NAF samples will likely shed light on NAF’s content and clinical potential. Here, we present a narrative review and perspectives of NAF research at a glance.

The importance of pro-social processing, and ameliorating dysfunction in schizophrenia. An FMRI study of oxytocin

Schizophrenia is often a severe and debilitating mental illness, frequently associated with impairments in social cognition that hinder individuals' abilities to relate to others and integrate effectively in society. Oxytocin has emerged as a putative therapeutic agent for treating social deficits in schizophrenia, but the mode of action remains unclear. This placebo-controlled crossover study aimed to elucidate the neural underpinnings of oxytocin administration in patients with schizophrenia. 20 patients with schizophrenia were examined using functional magnetic resonance imaging under oxytocin (40 IU) or placebo nasal spray. Participants performed a stochastically rewarded decision-making task that incorporated elements of social valence provided by different facial expressions, i.e. happy, angry and neutral. Oxytocin attenuated the normal bias in selecting the happy face accompanied by reduced activation in a network of brain regions that support mentalising, processing of facial emotion, salience, aversion, uncertainty and ambiguity in social stimuli, including amygdala, temporo-parietal junction, posterior cingulate cortex, precuneus and insula. These pro-social effects may contribute to the facilitation of social engagement and social interactions in patients with schizophrenia and warrant further investigation in future clinical trials for social cognitive impairments in schizophrenia.

Effect of oxytocin nasal spray on auditory automatic discrimination measured by mismatch negativity.

As a treatment for cognitive dysfunction in schizophrenia, oxytocin nasal sprays potentially improve social cognition, facial expression recognition, and sense of smell. Mismatch negativity (MMN) is an event-related potential (ERP) reflecting auditory discrimination while MMN deficits reflect cognitive function decline in schizophrenia. To determine whether oxytocin nasal spray affects auditory MMN METHODS: We measured ERPs in healthy subjects during an auditory oddball task, both before and after oxytocin nasal spray administration. Forty healthy subjects were randomly assigned to either the oxytocin or placebo group. ERPs were recorded during the oddball task for all subjects before and after a 24 international unit (IU) intranasal administration, and MMN was compared between the two groups. Participants who received oxytocin had significantly shorter MMN latencies than those who received a placebo. Oxytocin had no significant effect on the Change in MMN amplitude. The shortened MMN latencies that were observed after oxytocin nasal spray administration suggest that oxytocin may promote the comparison-decision stage.

The Transmutation of Disability to Disease: The Ethics of Autism Research

This paper will look at the ethics of research and treatment of autism, and how history and disability justice movements may inform our ethical stance as physicians. For this paper I will use autistics to refer to people with autism as this is the preferred language from those in the disability movement I will be citing. The central question, which may never be answered, is how can physicians ethically wield the power of pathologization in a society with rapidly advancing assistive technologies that throw into question what is and is not disability. Central to this presentation with be Georges Canguilhem’s writing in On The Normal and The Pathological, specifically his assertion that “health is life in the silence of the organs.” What does it mean when the organs, understood broadly as the body, “speak” to the individual but their presence as difference and even as disability does not translate to the patient as disease? The specific case I will look at is the engineering and testing of oxytocin nasal sprays on young children with autism (Kong, Lu 2020). Literature already exists critiquing medical institutions and health practitioners use of Applied Behavior Analysis (ABA) in the “treatment” of autism, as this form of therapy can be experienced by the participant as coercive, traumatic, and even violent (Yergeau 2018). Where this paper adds to the discussion is to further question the ethics of autism research even in cases where the proposed intervention, oxytocin nasal spray, poses minimal physical harm to the child. In medical ethics, is there a place for the historical abuses of autistics to inform our current practices? And furthermore is it the person/patient or the doctor who interpolates the person into the role of the patient? I will briefly engage with the debate concerning the dichotomization of the social and the medical model, critiqued by sociologist Tom Shakespeare, only insomuch as this paper is not arguing about the validity of those models but about how the medical model comes to be invoked and how the “patient” is produced.

Oxytocin increases emotional theory of mind, but only for low socioeconomic status individuals.

Studies have linked oxytocin to emotional theory of mind (eToM) — the ability to recognise and understand others' emotions. However, multiple replications have so far failed to reach a consistent result. Growing evidence suggests that oxytocin's positive effects on social-emotional tasks such as eToM are highly dependent on trait-level individual differences. In the present study, we theorised that socioeconomic status (SES) could influence oxytocin's impact on emotional mentalising processes. We tested our hypothesis in a double-blind between–subjects oxytocin nasal spray study on 147 Caucasian white male participants in the United Kingdom. In accordance with our hypothesis, we found that oxytocin (as compared to placebo) did boost emotional theory of mind, but only in people from low subjective SES backgrounds. Our results expand existing theory on how individual differences moderate oxytocin's role on social behaviours.

Probiotics and oxytocin nasal spray as neuro-social-behavioral interventions for patients with autism spectrum disorders: a pilot randomized controlled trial protocol

BackgroundAutism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in social interaction and communication. Oxytocin (OXT), as a neuropeptide, plays a role in emotional and social behaviors. Lactobacillus reuteri (L. reuteri) supplementation led to an OXT-dependent behavioral improvement in ASD mouse models. Despite some promising results from animal studies, little is known about the efficacy of supplementation with L. reuteri, alone or with exogenous OXT therapy, on social-behavioral functions in ASD patients. This paper presents a protocol for a pilot randomized controlled trial to evaluate the feasibility of conducting a full trial comparing oral supplementation of L. reuteri probiotics and intranasal OXT spray to placebo on the effect of social and behavioral functions in ASD patients. The study will also capture preliminary estimates of the efficacy of the proposed interventions in ASD patients.MethodsThis pilot trial is a two-staged, randomized, double-blind, placebo-controlled, parallel-group study. Throughout the study (0–24 weeks), 60 patients with ASD will be randomly assigned to receive either oral L. reuteri probiotics or placebo. In the second study stage (13–24 weeks), all participants will receive intranasal OXT spray. As primary outcomes, serum OXT levels will be assayed and social behaviors will be assessed via the Autism Behavior Checklist and the Social Responsiveness Scale which are validated questionnaires, an objective emotional facial matching test, and a new video-based eye-tracking test. Secondary outcomes include the GI-severity-index and Bristol Stool Chart to assess GI function and gut microbiome/short-chain fatty acids. All the outcomes will be assessed at baseline and weeks 12 and 24.DiscussionThis pilot study will provide important information on the feasibility of recruitment, blinding and concealment, treatment administration, tolerability and adherence, specimen collection, outcome assessment, potential adverse effects, and the preliminary efficacy on both primary and secondary outcomes. If successful, this pilot study will inform a larger randomized controlled trial fully powered to examine the efficacies of oral L. reuteri probiotics and/or intranasal OXT spray on social-behavioral improvement in ASD patients.Trial registrationClinicalTrials.gov, NCT03337035. Registered 8 November 2017.

High Dose Oxytocin Nasal Spray for Treatment of Tinnitus

High Dose Oxytocin Nasal Spray for Treatment of Tinnitus

Effects of Oxytocin on Placebo and Nocebo Effects in a Pain Conditioning Paradigm: A Randomized Controlled Trial

Oxytocin has been shown to increase trust, decrease anxiety, and affect learning as has been observed in conditioning paradigms. Trust, anxiety, and learning are important factors that influence placebo effects. In this study, we investigated whether oxytocin can increase placebo analgesia, decrease nocebo hyperalgesia, and influence extinction processes of both. Eighty male volunteers were assigned to a 40 IU of oxytocin nasal spray group, or to a placebo control group. Placebo analgesia and nocebo hyperalgesia were induced by a conditioning procedure in combination with verbal suggestions. The results demonstrate that the conditioning procedure successfully elicited significant placebo analgesia and nocebo hyperalgesia responses (P < .001). Furthermore, extinction was observed (P < .001), although placebo and nocebo responses did not return to baseline and remained significant. Oxytocin did not influence placebo analgesia or nocebo hyperalgesia and had no effect on extinction. This study provides support against the placebo-boosting effects of oxytocin and was the first one to demonstrate that it also did not influence nocebo effects or extinction processes, however, these results pertain to only a male sample. As managing placebo and nocebo effects has widespread clinical implications, further research should investigate other neurobiological or behavioral pathways to boost placebo and decrease nocebo effects. PerspectiveThe present study demonstrated that placebo analgesia and nocebo hyperalgesia can be successfully induced by conditioning and verbal suggestions. We could not confirm the hypothesis that oxytocin affects either of these phenomena. Other pharmacological agents and behavioral manipulations for increasing placebo and decreasing nocebo effects should be investigated.

Neural correlates of emotion processing comparing antidepressants and exogenous oxytocin in postpartum depressed women: An exploratory study.

Despite common use of antidepressants to treat postpartum depression, little is known about the impact of antidepressant use on postpartum brain activity. Additionally, although oxytocin has been investigated as a potential treatment for postpartum depression, the interaction between antidepressants and exogenous oxytocin on brain activity is unknown. We explored postpartum depressed women’s neural activation in areas identified as important to emotion and reward processing and potentially, antidepressant response: the amygdala, nucleus accumbens and ventral tegmental area. We conducted a secondary analysis of a functional imaging study of response to sexual, crying infant and smiling infant images in 23 postpartum depressed women with infants under six months (11 women taking antidepressants, 12 unmedicated). Participants were randomized to receive a single dose of oxytocin or placebo nasal spray. There was significantly higher amygdala activation to sexual stimuli than either neutral or infant-related stimuli among women taking antidepressants or receiving oxytocin nasal spray. Among unmedicated women receiving placebo, amygdala activation was similar across stimuli types. There were no significant effects of antidepressants nor oxytocin nasal spray on reward area processing (i.e., in the nucleus accumbens or ventral tegmental area). Among postpartum women who remain depressed, there may be significant interactions between the effects of antidepressant use and exogenous oxytocin on neural activity associated with processing emotional information. Observed effect sizes were moderate to large, strongly suggesting the need for further replication with a larger sample.

A 6-week repeated intranasal dose toxicity study of TTA-121, a novel oxytocin nasal spray, in rats

A 6-week repeated intranasal dose toxicity study of TTA-121, a novel oxytocin nasal spray, in rats

A 6-week repeated intranasal dose toxicity study of TTA-121, a novel oxytocin nasal spray, in cynomolgus monkeys

A 6-week repeated intranasal dose toxicity study of TTA-121, a novel oxytocin nasal spray, in cynomolgus monkeys

No side-effects of single intranasal oxytocin administration in middle childhood.

Despite growing interest in the (therapeutic) use of intranasal oxytocin administration in children, the potential side-effects of intranasal oxytocin have remained largely unclear to date. The current study is the first double-blind randomized controlled trial to examine side-effects following single administration of oxytocin nasal spray in elementary school-aged children. One hundred children (8-12years old) were randomly assigned to receive oxytocin or placebo nasal spray. We assessed side-effects by means of a standardized, drug-specific questionnaire and an open-ended question at two time points: 90min after nasal spray administration and 24h after administration. There were no significant associations between nasal spray condition and total frequency of reported side-effects or reports of specific side-effects. Children and their mothers were unable to correctly guess nasal spray allocation, further supporting that the subjective experience of oxytocin versus placebo nasal spray effects was similar. Moreover, the majority of reported side-effects were classified as mild and ceased within 24h after the procedure, indicating that the nasal sprays were well tolerated. In all, this study is the first randomized controlled trial to provide information on the safety of intranasal oxytocin administration in middle childhood. The current study suggests that single administration of intranasal oxytocin is likely safe in elementary school-aged children.

Nasal Oxytocin Treatment Biases Dogs' Visual Attention and Emotional Response toward Positive Human Facial Expressions.

The neuropeptide oxytocin plays a critical role in social behavior and emotion regulation in mammals. The aim of this study was to explore how nasal oxytocin administration affects gazing behavior during emotional perception in domestic dogs. Looking patterns of dogs, as a measure of voluntary attention, were recorded during the viewing of human facial expression photographs. The pupil diameters of dogs were also measured as a physiological index of emotional arousal. In a placebo-controlled within-subjects experimental design, 43 dogs, after having received either oxytocin or placebo (saline) nasal spray treatment, were presented with pictures of unfamiliar male human faces displaying either a happy or an angry expression. We found that, depending on the facial expression, the dogs’ gaze patterns were affected selectively by oxytocin treatment. After receiving oxytocin, dogs fixated less often on the eye regions of angry faces and revisited (glanced back at) more often the eye regions of smiling (happy) faces than after the placebo treatment. Furthermore, following the oxytocin treatment dogs fixated and revisited the eyes of happy faces significantly more often than the eyes of angry faces. The analysis of dogs’ pupil diameters during viewing of human facial expressions indicated that oxytocin may also have a modulatory effect on dogs’ emotional arousal. While subjects’ pupil sizes were significantly larger when viewing angry faces than happy faces in the control (placebo treatment) condition, oxytocin treatment not only eliminated this effect but caused an opposite pupil response. Overall, these findings suggest that nasal oxytocin administration selectively changes the allocation of attention and emotional arousal in domestic dogs. Oxytocin has the potential to decrease vigilance toward threatening social stimuli and increase the salience of positive social stimuli thus making eye gaze of friendly human faces more salient for dogs. Our study provides further support for the role of the oxytocinergic system in the social perception abilities of domestic dogs. We propose that oxytocin modulates fundamental emotional processing in dogs through a mechanism that may facilitate communication between humans and dogs.

Tinnitus Treatment with Oxytocin: A Pilot Study.

Tinnitus is the perception of sound in the absence of an external stimulus. It is a frequent condition for which there is as yet no pharmacological treatment approved. Auditory and non-auditory pathways are involved in tinnitus' pathophysiology. Oxytocin is a neurohormone and eventual neurotransmitter that plays a complex role in social cognition and behavior. To evaluate the potential of oxytocin as a tinnitus treatment. Two studies were performed. Study 1 was a long-term open pilot study, while study 2 investigated short-term effects with a double-blinded placebo-controlled cross-over study. Ambulatory ENT care. In study 1, 15 patients were investigated over a 10-week period in an open pilot study. In study 2, 16 patients were included in a placebo-controlled crossover trial to investigate short-term effects following a single dose. For the long-term study (study 1), analysis of variance revealed a significant decrease in tinnitus sensation, both for the Tinnitus Handicap Inventory and Clinical Global Impression (CGI). Also, the short-term effects in study 2 revealed a significant reduction of tinnitus because of the oxytocin nasal spray as measured with the Visual Analog Scale and the CGI Scale. These preliminary studies demonstrated that oxytocin may represent a helpful tool for treating tinnitus and further larger controlled studies are warranted.