Effects Of Intranasal Oxytocin Research Articles

A randomized placebo-controlled intranasal oxytocin study on first impressions and reactions to social rejection

Oxytocin is central to pair-bonding in non-human animals. We assessed effects of intranasal oxytocin on bond formation between two opposite-sex strangers. In a double-blind placebo-controlled design, 50 pairs of one man and one woman received oxytocin or placebo spray intranasally. After treatment, they played a social interaction game, followed by tasks designed to measure first impressions of the opposite-sex co-participant, and a virtual ball-tossing game (cyberball), designed to measure reactions to rejection by the co-participant. We found no evidence that intranasal oxytocin can improve first impressions of an opposite-sex stranger, and some Bayesian support against this hypothesis. For rejection sensitivity, we observed a sex-and-context-dependent drug effect on post-ostracism mood ratings, consistent with recent studies indicating that interindividual variation and social context can interact with intranasal oxytocin effects. Further research is needed to determine the generalisability of these findings, i.e. if oxytocin can improve first impressions in humans under different conditions.

Depressive symptoms and social context modulate oxytocin's effect on negative memory recall.

Oxytocin promotes social affiliation across various species, in part by altering social cognition to facilitate approach behaviour. However, the effects of intranasal oxytocin on human social cognition are mixed, perhaps because its effects are context dependent and subject to inter-individual differences. Few studies have included explicit manipulations of social context to test this supposition. We examined oxytocin’s effects on autobiographical memory recall in two contexts, with and without social contact, and evaluated whether these effects were moderated by depressive symptoms. Two non-clinical samples (Study 1, n = 48; Study 2, n = 63) completed randomised, placebo-controlled, within-subject experiments. We assessed autobiographical memory recall across two sessions (intranasal oxytocin or placebo) and two contexts (memories elicited by an experimenter or by computer). Overall, intranasal oxytocin increased ratings of the vividness of recalled memories during the social context only. Individuals with elevated depressive symptoms also recalled memories that were more negative following oxytocin relative to placebo only in the non-social context across the two studies. Findings highlight the negative consequences of increasing oxytocin bioavailability in vulnerable persons in the absence of social contact. Contextual factors such as social isolation among depressed populations may complicate the clinical use of oxytocin.

Age and intranasal oxytocin effects on trust-related decisions after breach of trust: Behavioral and brain evidence.

Age-related differences in cognition and socioemotional functions, and in associated brain regions, may reduce sensitivity to cues of untrustworthiness, with effects on trust-related decision making and trusting behavior. This study examined age-group differences in brain activity and behavior during a trust game. In this game, participants received "breach-of-trust" feedback after half of the trials. The feedback indicated that only 50% of the monetary investment into their fellow players had resulted in returns. The study also explored the effects of intranasal oxytocin on trust-related decisions in aging, based on suggestions of a modulatory role of oxytocin in response to negative social stimuli and perceptions of trust. Forty-seven younger and 46 older participants self-administered intranasal oxytocin or placebo, in a randomized, double-blind, between-subjects procedure, before they engaged in the trust game while undergoing functional magnetic resonance imaging (fMRI). Younger participants invested less into their game partners after breach-of-trust feedback, while older participants showed no significant difference in their investment after breach-of-trust feedback. Oxytocin did not modulate the behavioral effects. However, after breach-of-trust feedback, older participants in the oxytocin group showed less activity in the left superior temporal gyrus. In contrast, older participants in the placebo group showed more activity in left superior temporal gyrus after breach of trust. The findings may reflect reduced responsiveness to cues of untrustworthiness in older adults. Furthermore, the modulatory effect of oxytocin on left superior temporal gyrus activity among older adults supports the neuropeptide's age-differential role in neural processes in aging, including in the context of trust-related decision making. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Supplemental Material for Age and Intranasal Oxytocin Effects on Trust-Related Decisions After Breach of Trust: Behavioral and Brain Evidence

Supplemental Material for Age and Intranasal Oxytocin Effects on Trust-Related Decisions After Breach of Trust: Behavioral and Brain Evidence

The Effects of Intranasal Oxytocin on Neural and Behavioral Responses to Social Touch in the Form of Massage.

Manually-administered massage can potently increase endogenous oxytocin concentrations and neural activity in social cognition and reward regions and intranasal oxytocin can increase the pleasantness of social touch. In the present study, we investigated whether intranasal oxytocin modulates behavioral and neural responses to foot massage applied manually or by machine using a randomized placebo-controlled within-subject pharmaco-fMRI design. 46 male participants underwent blocks of massage of each type where they both received and imagined receiving the massage. Intranasal oxytocin significantly increased subjective pleasantness ratings of the manual but not the machine massage and neural responses in key regions involved in reward (orbitofrontal cortex, dorsal striatum and ventral tegmental area), social cognition (superior temporal sulcus and inferior parietal lobule), emotion and salience (amygdala and anterior cingulate and insula) and default mode networks (medial prefrontal cortex, parahippocampal gyrus, posterior cingulate, and precuneus) as well as a number of sensory and motor processing regions. Both neural and behavioral effects of oxytocin occurred independent of whether subjects thought the massage was applied by a male or female masseur. These findings support the importance of oxytocin for enhancing positive behavioral and neural responses to social touch in the form of manually administered massage and that a combination of intranasal oxytocin and massage may have therapeutic potential in autism.Clinical Trials RegistrationThe Effects of Oxytocin on Social Touch; registration ID: NCT03278860; URL: https://clinicaltrials.gov/ct2/show/NCT03278860.

Intranasal (IN) Oxytocin Relieves Pain and Depressive Behavior in a Rodent Model of Mild Traumatic Brain Injury (TBI)

Evaluate the efficacy of intranasal oxytocin in relieving pain and associated depressive behavior in a rat model of mild TBI. Pain, anxiety, depression and cognitive impairment after TBI are sources of long-term disability for which there is no effective treatment. Decreases in endogenous oxytocin are associated with chronic pain and headache, and exogenous oxytocin reduces both pain and depressive behavior in animals and humans. This study examined the effects of intranasal oxytocin in pain and depressive behavior following TBI in rats. A standardized, reproducible, lateral fluid percussion rat model was employed using male Sprague-Dawley rats. Sham animals underwent the same procedure as the TBI animals except for the pressure pulse upon the dura. At 48-hour post procedure and establishment of hind paw and facial allodynia, 6 rats received IN oxytocin, 6 received IN vehicle. In 12 other rats, 16 ug oxytocin or vehicle was administered intravenously (IV). An additional 6 rats each received either IN oxytocin plus intraperitoneal (IP) oxytocin receptor antagonist atosiban or oxytocin plus vehicle. Rats were assessed on mechanical allodynia, conditioned place preference, and the forced swim test (FST). Oxytocin concentrations in trigeminal ganglia (TG), pons, spinal cord, and olfactory bulb were measured by ELISA immunoassay. IN oxytocin, but not IV or vehicle, attenuated both reactive and spontaneous pain following mild TBI as well as depressive behavior upon FST. This effect was blocked by atosiban, confirming an effect via oxytocin receptors. Immunoassay demonstrated concentrating of oxytocin primarily in TG. IN oxytocin was effective in relieving pain and associated depressive behavior of TBI in this model and has potential to be a safe and effective treatment for TBI headaches and post-concussion syndrome.

Intranasal oxytocin decreases self-oriented learning.

Oxytocin has been found to play an important role in human social cognition and social interaction. Over the last two decades, surge studies have been conducted to investigate how oxytocin impacts other-oriented processes, such as trust and generosity (Zak et al. in PLoS ONE 2(11):e1128, 2007); however, the examination of the effect of oxytocin on self-related processes was relatively inadequate. Appropriate and efficient social interactions require both self- and other-related information processing. Recent studies have found that intranasal oxytocin (IN-OT) influences the self-related process, although the results have been mixed. The computational process underlying the effects of IN-OT on self-processing remains unknown. We aim to investigate the effect of IN-OT on self-oriented learning across different contexts (self-other independent vs. self-other dependent) and uncover the process by which IN-OT affects dynamic behavior changes. We performed two double-blind, placebo-controlled studies and used reinforcement learning theory to integrate action and related feedback for participants' behaviors. In study 1, IN-OT decreased self-oriented reward learning when self-oriented learning and prosocial (other-oriented) learning were assessed separately. These effects were partially due to the OT-related increase in choice variability during self-oriented learning. In study 2, IN-OT also decreased learning performance during self-oriented reward learning when self-related and other-related rewards were present together. These effects occurred at an early stage of the learning process and could be moderated by the participants' social value orientation. Our findings show that OT attenuates the process of self-oriented learning and provides an underlying computational process. Our findings shed new light on the dynamics of IN-OT's effects on human self-oriented learning processes. For future studies on OT effects on self-oriented learning, individual factors such as social value orientation should be taken into consideration in research development and analysis.

Intranasal oxytocin attenuates insula activity in response to dynamic angry faces

The effects of intranasal oxytocin on amygdala activity during emotional perception are often mixed. Given that the brain is organized into networks of interconnected areas, functional connectivity might provide an effective way to further understand the oxytocin effect. The aim of the present study was to investigate whether oxytocin administration affects amygdala activity and its functional connectivity during dynamic facial expression perception. Using a between-group, double-blind, placebo-controlled design, 55 participants were randomly assigned to groups receiving a single dose of 24 IU oxytocin or a placebo via intranasal administration. An implicit emotional task was employed to investigate the effect of oxytocin on neural responses to dynamic angry, neutral, and happy facial expressions with fMRI. Participants were instructed to respond only when the inverted dynamic faces were presented. The results indicated that oxytocin attenuated activation of insula and emotional processing-related regions (e.g., ACC, thalamus, and MFG) during the viewing of dynamic angry faces. However, functional connectivity between the regions involved in the perception of dynamic angry faces was not changed following oxytocin administration. The present findings may contribute to our understanding of the anxiolytic effects of oxytocin and eventually facilitate human clinical applications.

The effect of intranasal oxytocin on visual processing and salience of human faces

The mechanisms underlying the role of oxytocin (OT) as a regulator of social behavior in mammals are only partly understood. Recently, it has been proposed that OT increases the salience of social stimuli. We carried out a randomized, double-blind, cross-over study of the effects of OT on binocular rivalry, a visual phenomenon underpinned by the interplay of excitation and inhibition in the cortex. A final sample of 45 participants viewed images of social stimuli (faces with different emotional expressions) and non-social stimuli (houses and Gabor patches). We demonstrate a robust effect that intranasal OT increases the salience of human faces in binocular rivalry, such that dominance durations of faces are longer—this effect is not modulated by the facial expression. We tentatively show that OT treatment increases dominance durations for non-social stimuli. Our results lend support to the social salience hypothesis of OT, and in addition offer provisional support for the role of OT in influencing excitation-inhibition balance in the brain.

Potential shortcomings in current studies on the effect of intranasal oxytocin in Anorexia Nervosa and healthy controls - A systematic review and meta-analysis.

The psychopathology of anorexia nervosa (AN) includes altered social cognition and information processing of fear and anxiety. Oxytocin, a neuromodulating hormone, may influence these functions and could be valuable for the treatment of AN. The current study aimed at reviewing the effect of intranasal oxytocin (IN-OT) on attentional bias (AB) and emotion recognition (ER) in AN. A systematic literature review was done for free-text and the MeSH-terms: anorexia nervosa, feeding and eating disorders, and oxytocin. Six publications, reporting from 4 unique clinical trials, were included in this review. A meta-analysis was conducted to examine the effects of IN-OT on AB towards food images and ER on healthy controls (HC) and patients with AN. Overall, IN-OT did not influence AB towards food images (effect size = 0.20 [- 0.16, 0.57], p = 0.28) and had no effect on ER (effect size = - 0.01 [- 0.27, 0.26], p = 0.97) in patients with AN and healthy control (HC) subjects collectively. Assessing HC and AN separately in subgroup analyses did not show any significant effect on AB and ER in neither of the subgroups. All tests were done between 15 and 55 min post-administration of IN-OT, while peak concentration in the cerebrospinal fluid has been determined to be at 75 min. The current level of evidence is moderate showing no effect of IN-OT on AB or ER in AN. However, brain exposure may not have been sufficient which future studies with IN-OT need to ensure by considering dose and dose-to-task interval.

Coding Errors Lead to Unsupported Conclusions

We have detected coding errors in the meta-analysis of Hofmann et al. (2015) who investigated the effect of intranasal oxytocin on psychiatric symptoms. We demonstrate that, after correcting these errors and reanalysing the data, the main conclusions of Hofmann et al. (2015) are no longer supported.

How Can Intranasal Oxytocin Research Be Trusted? A Systematic Review of the Interactive Effects of Intranasal Oxytocin on Psychosocial Outcomes

Over the past two decades, research about the role of oxytocin (OT) in human behavior has grown exponentially. However, a unified theory of OT effects has yet to be developed. Relatedly, growing concerns about the robustness of conclusions drawn in the field have been raised. The current article contributes to this debate by reporting on and discussing key conclusions from a systematic review of published studies addressing the interactive effects of intranasal OT (IN-OT) administration on psychosocial outcomes in a healthy population. The review indicates that (a) tested interactive IN-OT effects were highly heterogeneous; (b) for most published interactions, no replication was attempted; (c) when attempted, replications were largely unsuccessful; (d) significance was unrelated to sample size; (e) statistical power was critically low and unrelated to the rate of significant results; and (f) research practices were characteristic of an exploratory approach. This concerning state of affairs makes it virtually impossible to tease apart true from false interactive IN-OT effects. We provide constructive directions on the basis of this observation and positive predictive value simulations for future research that should help extract true effects from noise and move the IN-OT field forward.

Investigating resting brain perfusion abnormalities and disease target-engagement by intranasal oxytocin in women with bulimia nervosa and binge-eating disorder and healthy controls

Advances in the treatment of bulimia nervosa and binge-eating disorder (BN/BED) have been marred by our limited understanding of the underpinning neurobiology. Here we measured regional cerebral blood flow (rCBF) to map resting perfusion abnormalities in women with BN/BED compared with healthy controls and investigate whether intranasal oxytocin (OT), proposed as a potential treatment, can restore perfusion in disorder-related brain circuits. Twenty-four women with BN/BED and 23 healthy women participated in a randomized, double-blind, crossover, placebo-controlled study. We used arterial spin labelling MRI to measure rCBF and the effects of an acute dose of intranasal OT (40 IU) or placebo over 18–26 min post dosing, as we have previously shown robust OT-induced changes in resting rCBF in men in a similar time-window (15–36 min post dosing). We tested for effects of treatment, diagnosis and their interaction on extracted rCBF values in anatomical regions-of-interest previously implicated in BN/BED by other neuroimaging modalities, and conducted exploratory whole-brain analyses to investigate previously unidentified brain regions. We demonstrated that women with BN/BED presented increased resting rCBF in the medial prefrontal and orbitofrontal cortices, anterior cingulate gyrus, posterior insula and middle/inferior temporal gyri bilaterally. Hyperperfusion in these areas specifically correlated with eating symptoms severity in patients. Our data did not support a normalizing effect of intranasal OT on perfusion abnormalities in these patients, at least for the specific dose (40 IU) and post-dosing interval (18–26 min) examined. Our findings enhance our understanding of resting brain abnormalities in BN/BED and identify resting rCBF as a non-invasive potential biomarker for disease-related changes and treatment monitoring. They also highlight the need for a comprehensive investigation of intranasal OT pharmacodynamics in women before we can fully ascertain its therapeutic value in disorders affecting predominantly this gender, such as BN/BED.

Oxytocin biases eye-gaze to dynamic and static social images and the eyes of fearful faces: associations with trait autism

A key functional effect of intranasal oxytocin with potential therapeutic relevance for autism-spectrum disorder is its reported facilitation of attention towards social stimuli, notably the eye region of faces. In the current randomized placebo-controlled within-subject experiment on 40 healthy males, we investigated the robustness of this facilitation of attention by intranasal oxytocin (24IU) towards social cues. Eye-tracking measures of preference for dynamic and static social vs. non-social stimuli were taken in four different paradigms where autistic individuals tend to exhibit reduced interest in social stimuli. Additionally, we investigated whether oxytocin increases attention towards the eyes relative to other salient face regions in an emotional face paradigm. Results showed that the time spent viewing both dynamic and static social vs. non-social stimuli was negatively associated with trait autism and significantly increased following intranasal oxytocin. For face stimuli, oxytocin primarily increased gaze towards the eyes of fearful expression faces but not for other face emotions. Overall, our findings demonstrate that oxytocin significantly shifts gaze preference towards social vs. non-social stimuli and to the eyes of fearful faces. Importantly, oxytocin appears generally to shift attention more towards salient social stimuli of particular relevance in the context of autism providing further support for its potential therapeutic use in autism-spectrum disorder.

Actigraphy assessment of motor activity and sleep in patients with alcohol withdrawal syndrome and the effects of intranasal oxytocin.

The alcohol withdrawal syndrome increases autonomic activation and stress in patients during detoxification, leading to alterations in motor activity and sleep irregularities. Intranasal oxytocin has been proposed as a possible treatment of acute alcohol withdrawal. The aim of the present study was to explore whether actigraphy could be used as a tool to register symptoms during alcohol detoxification, whether oxytocin affected actigraphy variables related to motor activity and sleep compared to placebo during detoxification, and whether actigraphy-recorded motor function during detoxification was different from that in healthy controls. This study was a part of a randomized, double blind, placebo-controlled trial in which 40 patients with alcohol use disorder admitted for acute detoxification were included. Of these, 20 received insufflations with intranasal oxytocin and 20 received placebo. Outcomes were actigraphy-recorded motor activity during 5-hour sequences following the insufflations and a full 24-hour period, as well as actigraphy-recorded sleep. Results were related to clinical variables of alcohol intake and withdrawal, including self-reported sleep. Finally, the actigraphy results were compared to those in a group of 34 healthy individuals. There were no significant differences between the oxytocin group and the placebo group for any of actigraphy variables registered. Neither were there any correlations between actigraphy-recorded motor function and clinical symptoms of alcohol withdrawal, but there was a significant association between self-reported and actigraphy-recorded sleep. Compared to healthy controls, motor activity during alcohol withdrawal was lower in the evenings and showed increased variability. Intranasal oxytocin did not affect actigraphy-recorded motor activity nor sleep in patients with acute alcohol withdrawal. There were no findings indicating that actigraphy can be used to evaluate the degree of withdrawal symptoms during detoxification. However, patients undergoing acute alcohol withdrawal had a motor activity pattern different from than in healthy controls.

The Role of the Oxytocin System in Anxiety Disorders.

Oxytocin, a neuropeptide synthesized by the hypothalamus, plays a central role in human social behavior, social cognition, anxiety, mood, stress modulation, and fear learning and extinction. The relationships between oxytocin and psychiatric disorders including depression, anxiety, schizophrenia, and autism spectrum disorder have been extensively studied. In this chapter, we focus on the current knowledge about oxytocin and anxiety disorder. We discuss the anxiolytic effects of oxytocin in preclinical and clinical findings, possible related neurobehavioral mechanisms (social cognition, fear learning, and extinction), related neurotransmitter and neuroendocrine systems (hypothalamus-pituitary-adrenal axis, serotoninergic, and GABAergic systems), and studies regarding plasma levels of oxytocin, genetic and epigenetic findings, and effects of intranasal oxytocin in DSM-5 anxiety disorder (primarily social anxiety disorder and separation anxiety disorder) patients.

Intranasal Administration of Oxytocin Attenuates Stress Responses Following Chronic Complicated Stress in Rats.

Background/AimsGastrointestinal (GI) symptoms may develop when we fail to adapt to various stressors of our daily life. Central oxytocin (OXT) can counteract the biological actions of corticotropin-releasing factor (CRF), and in turn attenuates stress responses. Administration (intracerebroventricular) of OXT significantly antagonized the inhibitory effects of chronic complicated stress (CCS) on GI dysmotility in rats. However, intracerebroventricular administration is an invasive pathway. Intranasal administration can rapidly deliver peptides to the brain avoiding stress response. The effects of intranasal OXT on hypothalamus-pituitary-adrenal axis and GI motility in CCS conditions have not been investigated.MethodsA CCS rat model was set up, OXT 5, 10, or 20 μg were intranasal administered, 30 minutes prior to stress loading. Central CRF and OXT expression levels were analyzed, serum corticosterone and OXT concentrations were measured, and gastric and colonic motor functions were evaluated by gastric emptying, fecal pellet output, and motility recording system.ResultsRats in CCS condition showed significantly increased CRF expression and corticosterone concentration, which resulted in delayed gastric emptying and increased fecal pellet output, attenuated gastric motility and enhanced colonic motility were also recorded. OXT 10 μg or 20 μg significantly reduced CRF mRNA expression and the corticosterone concentration, OXT 20 μg also helped to restore GI motor dysfunction induced by CCS.ConclusionIntranasal administration of OXT has an anxiolytic effect and attenuates the hypothalamus-pituitary-adrenal axis in response to CCS, and gave effects which helped to restore GI dysmotility, and might be a new approach for the treatment of stress-induced GI motility disorders.

The acute effects of intranasal oxytocin on EEG mu responses to emotional faces

The acute effects of intranasal oxytocin on EEG mu responses to emotional faces

Sex-specific effects of intranasal oxytocin on intergroup competition

Sex-specific effects of intranasal oxytocin on intergroup competition

Intranasal administration of oxytocin decreases task-related aggressive responses in healthy young males

Aggression and distrust are often challenging problems in mental health treatment. Converging evidence reveals that oxytocin increases trust in social interactions and decreases fear of social betrayal. However, oxytocin has also been associated with protective behavior and, as such, might increase defensive aggressive reactions.In this randomized double-blind, placebo-controlled study, the effects of intranasal oxytocin (32IU) on task-related aggressive responses were measured using the Point Subtraction Aggression Paradigm (PSAP). Fifty-seven healthy males were enrolled and randomized to oxytocin (N = 30) or placebo (n = 27). Salivary oxytocin, cortisol and testosterone were measured serially prior to the intervention, and then before and after the PSAP, to evaluate the effects of oxytocin administration on hormonal functioning in relation to aggression. In addition, oxytocin was measured in urine collected directly after the experimental task, reflecting the 2 h period after oxytocin or placebo administration.The proportion of aggressive responses to the PSAP was significantly lower in participants receiving oxytocin versus placebo (β= -0.46, P = 0.01). No significant effect of oxytocin was found regarding defensive reactions. Urinary oxytocin was negatively associated with the proportion of aggressive responses to the PSAP in both the oxytocin and the placebo group (β= -0.02, P < 0.01), suggesting that higher levels of urinary oxytocin corresponded with reduced aggressive responding. Our results indicate that oxytocin administration reduces aggressive behavior in healthy young men. Moreover, increased endogenous urinary oxytocin is associated with less aggressive responding. Taken together, these findings suggest that oxytocin signaling has a causal influence on aggressive behavior.