Effects Of Intranasal Oxytocin Administration Research Articles

Oxytocin enhances the appropriate use of human social cues by the domestic dog (Canis familiaris) in an object choice task

It has been postulated that the neuropeptide, oxytocin, is involved in human-dog bonding. This may explain why dogs, compared to wolves, are such good performers on object choice tasks, which test their ability to attend to, and use, human social cues in order to find hidden food treats. The objective of this study was to investigate the effect of intranasal oxytocin administration, which is known to increase social cognition in humans, on domestic dogs' ability to perform such a task. We hypothesised that dogs would perform better on the task after an intranasal treatment of oxytocin. Sixty-two (31 males and 31 females) pet dogs completed the experiment over two different testing sessions, 5-15 days apart. Intranasal oxytocin or a saline control was administered 45 min before each session. All dogs received both treatments in a pseudo-randomised, counterbalanced order. Data were collected as scores out of ten for each of the four blocks of trials in each session. Two blocks of trials were conducted using a momentary distal pointing cue and two using a gazing cue, given by the experimenter. Oxytocin enhanced performance using momentary distal pointing cues, and this enhanced level of performance was maintained over 5-15 days time in the absence of oxytocin. Oxytocin also decreased aversion to gazing cues, in that performance was below chance levels after saline administration but at chance levels after oxytocin administration.

A meta-analytic review of the impact of intranasal oxytocin administration on cortisol concentrations during laboratory tasks: moderation by method and mental health.

A large body of research has examined the acute effects of intranasal oxytocin administration on social cognition and stress-regulation. While progress has been made with respect to understanding the effect of oxytocin administration on social cognition in clinical populations (e.g. autism, schizophrenia), less is known about its impact on the functioning of the hypothalamic-pituitary-adrenal (HPA) axis among individuals with a mental disorder. We conducted a meta-analysis on the acute effect of intranasal oxytocin administration on the cortisol response to laboratory tasks. The search yielded eighteen studies employing a randomized, placebo-controlled design (k=18, N=675). Random-effects models and moderator analyses were performed using the metafor package for the statistical program R. The overall effect size estimate was modest and not statistically significant (Hedges g=-0.151, p=0.11) with moderate heterogeneity in this effect across studies (I(2)=31%). Controlling for baseline differences in cortisol concentrations, moderation analyses revealed that this effect was larger in response to challenging laboratory tasks that produced a robust stimulation of the HPA-axis (Hedges g=-0.433, 95% CI[-0.841, -0.025]), and in clinical populations relative to healthy controls (Hedges g=-0.742, 95% CI[-1.405, -0.078]). Overall, oxytocin administration showed greater attenuation of the cortisol response to laboratory tasks that strongly activated the HPA-axis, relative to tasks that did not. The effect was more robust among clinical populations, suggesting possible increased sensitivity to oxytocin among those with a clinical diagnosis and concomitant social difficulties. These data support the view that oxytocin may play an important role in HPA dysfunction associated with psychopathology.

Effects of intranasal oxytocin administration on memory for infant cues: Moderation by childhood emotional maltreatment

Oxytocin has been implicated in parent–infant attachment and social recognition. With respect to emotion recognition memory, both memory-enhancing and impairing effects have been observed, suggesting an influence of individual factors. We assessed the effects of oxytocin on memory for infant cues, and whether these effects are moderated by self-reported childhood emotional maltreatment. Nulliparous females (N = 102) participated in a randomized, double-blind, between-subjects study with intranasal oxytocin or placebo administration. Participants’ memory was tested using the Baby Social Reward Task, where participants were asked to select the happier infant from a pair of two infants based on the information that they received about the infants’ mood in the previous phase. Participants reporting more childhood emotional maltreatment were less accurate in this task after inhaling oxytocin. Our findings add to a growing body of literature showing that the effects of intranasal oxytocin on memory and social behavior are moderated by adverse early life experiences.

Oxytocin makes females, but not males, less forgiving following betrayal of trust.

Although oxytocin has been shown to enhance trust behavior, to date no study has directly established whether oxytocin can modulate the effect of repair strategies on restoring damaged trust. In the current double-blind, between-subjects, placebo-controlled design study, two repair strategies were used to examine the effect of intranasal oxytocin administration on modulating trust restoration in a revised trust game. The results showed that although oxytocin had no overall effect on modulating trust restoration, it did have a significant gender specific effect. Female subjects showed less evidence for trust repair in the oxytocin compared with the placebo treatment group. This suggests that oxytocin may make female subjects exhibit more punitive behavior towards partners who violate their trust and less sensitive to repair strategies provided by them. Interestingly, this gender specific effect was more evident in the context of attempted trust repair using financial compensation. However, it also extended to both apology alone and no compensation conditions, but not to the fair one, in females exhibiting high trait forgiveness. Thus females with a more forgiving attitude towards betrayal may actually be more likely to punish betrayal following oxytocin treatment.

(340) Intranasal oxytocin decreases anxiety and enhances endogenous pain inhibition

Preliminary evidence suggests that intranasal oxytocin may be a safe and effective analgesic with far reaching applicability. However, this limited previous research has lacked methodological rigor. A separate and stronger evidence base underscores the efficacy of intranasal oxytocin for alleviating anxiety while enhancing psychological well-being. Better understanding the role of oxytocin in endogenous pain modulation and pain-related mood states may highlight novel mechanisms associated with analgesia. The current study examined the effects of intranasal oxytocin administration on endogenous pain inhibitory processes as well as anxiety using a placebo-controlled, double-blind, within-subjects crossover design. Thus far, 24 of an expected 30 (38% female) pain-free, young adults have completed three laboratory sessions on three consecutive days. The first session represented the baseline assessment of endogenous pain inhibition via conditioned pain modulation (CPM). CPM was tested using algometry (test stimulus) and cold pressor (conditioning stimulus). During the second and third study sessions, participants initially completed the State-Trait Anxiety Inventory (STAI) and then self-administered a single (40IU/1mL) dose of placebo or intranasal oxytocin in random order. Thirty minutes following administration, participants again completed the STAI and repeated assessment of CPM. Results showed a non-significant decrease in anxiety following placebo administration (t23 = 1.14, p = .27); however, anxiety did significantly decrease following the administration of oxytocin (t23 = 2.32, p = .03). Further, there was a significant increase in CPM across the three study sessions (F2,46 = 3.94, p = .03). Specifically, CPM was significantly increased following administration of oxytocin relative to baseline (F1,23 = 5.57, p = .02). Although CPM was greater following administration of oxytocin compared to placebo, this difference was not statistically significant (F1,23 = 2.50, p = .13). These data tentatively suggest that the administration of intranasal oxytocin yields anxiolytic effects and also augments endogenous pain inhibitory capacity.

Oxytocin administration, salivary testosterone, and father–infant social behavior

The growing involvement of fathers in childcare is followed by an increased interest in the neurobiology of fatherhood; yet, experimental work on the neuroendocrine basis of paternal care in humans is limited. The steroid Testosterone (T) and the neuropeptide Oxytocin (OT) have each been implicated in complex social behavior including parenting. However, no study to date explored the interaction between these two hormones in the context of fathering. In the current study we first test the relationship between father's basal salivary T and father and infant's social behaviors during parent-child interaction. Second, we examine the effects of intranasal OT administration on father's T production, and, finally, address the relations between OT-induced change in father's T with father-infant social behavior. Thirty-five fathers and their infants participated in a double-blind, placebo-controlled, within-subject study. Father-infant interaction was micro-coded for paternal and infant social behavior and synchrony was measured as the coordination between their gaze, affect, and vocalizations. Father's salivary T levels were measured at baseline and three times after administration. Results indicate that lower baseline T correlated with more optimal father and infant's behaviors. OT administration altered T production in fathers, relative to the pattern of T in the placebo condition. Finally, OT-induced change in T levels correlated with parent-child social behaviors, including positive affect, social gaze, touch, and vocal synchrony. Findings support the view that neuroendocrine systems in human males evolved to support committed parenting and are the first to describe the dynamic interactions between OT and T within a bio-behavioral synchrony model.

Oxytocin effects on complex brain networks are moderated by experiences of maternal love withdrawal

The neuropeptide oxytocin has been implicated in a variety of social processes. However, recent studies indicate that oxytocin does not enhance prosocial behavior in all people in all circumstances. Here, we investigate effects of intranasal oxytocin administration on intrinsic functional brain connectivity with resting state functional magnetic resonance imaging. Participants were 42 women who received a nasal spray containing either 16 IU of oxytocin or a placebo and reported how often their mother used love withdrawal as a disciplinary strategy involving withholding love and affection after a failure or misbehavior. We found that oxytocin changes functional connectivity between the posterior cingulate cortex (PCC) and the brainstem. In the oxytocin group there was a positive connectivity between these regions, whereas the placebo group showed negative connectivity. In addition, oxytocin induced functional connectivity changes between the PCC, the cerebellum and the postcentral gyrus, but only for those participants who experienced low levels of maternal love withdrawal. We speculate that oxytocin enhances prosocial behavior by influencing complex brain networks involved in self-referential processing and affectionate touch, most prominently in individuals with supportive family backgrounds.

Frontiers in oxytocin science: from basic to practice

Oxytocin is a paramount social hormone in mammals and accumulating evidence also strengthens a leading role of this nonapeptide in human social behavior. From voles to men, oxytocin modulates an intriguing number of social behaviors that resonates across species. Behaviors modulated by oxytocin include the quality of pair bonding, parenting, social stress, in-group and out-group relationships, and social communications. Recent molecular genetic studies of the human oxytocin receptor (OXTR) gene have strengthened the evidence regarding the role of this nonapeptide in a range of normal and pathological human behaviors. Moreover, dysfunctions in the oxytocin neural pathways are likely contributing to deficits in social skills and communication in several psychiatric disorders. Indeed, a growing number of clinical studies are now testing the therapeutic effect of intranasal oxytocin administration in mental disorders- from autism to schizophrenia. Our social behavior is extraordinarily complex and is mediated by multiple and overlapping systems. Thus, it remains a challenging task to understand the neurobiology and neuroendocrinology underlying this complexity. One of the important determinants of human social behavior is the oxytocin system, which has provided a uniquely promising avenue of research toward revealing the tapestry of these complex social phenotypes. This Research Topic provide a broad view of the current state of oxytocin science in humans and illustrate how pharmacological, genetic, and neuroimaging strategies can be successfully combined toward unraveling the mystery of how human social behavior is regulated. Part A provides several review articles outlining salient facets of current oxytocin research. Lopatina et al. (2013) focus on translational approaches and show how rodent models elucidate the roles of the OXTR and CD38 genes in social behaviors. This review generates new perspectives in clinical therapies for diseases characterized by deficits in social cognition. Kumsta et al. (2013) provide an overview of the functional importance of OXTR promoter region methylation and summarizes a group of epigenetic studies that reveal the role of OXTR methylation signatures in shaping behavioral phenotypes. Quintana et al. (2013) highlight a key role for autonomic cardiac control in social behavior and psychiatric disorders and suggest the intriguing idea that autonomic cardiac control may moderate the relationship between oxytocin and social behavior. MacDonald (2013) discusses three factors that can influence individual responses to intranasal administration of oxytocin; sex and hormonal status, genetic variation, and attachment history. Finally, MacDonald and Feifel (2013) discuss the promise of oxytocin-based therapeutics and identify 10 key questions that future oxytocin research should address to facilitate oxytocin use in clinical medicine and truly deliver this molecule's therapeutic potential. Part B provides several research articles from basic methodology to the powerful strategy combining molecular genetics and neuroimaging, so-called imaging genomics. van IJzendoorn et al. (2012) address the important question of how long salivary oxytocin levels remain elevated following intranasal administration and further examine the effect of different doses of oxytocin administration. Kret and De Dreu (2013) explore the effect of intranasal oxytocin in the context of group formation and further consider the effect of fetal testosterone and empathic concern on this process. Fischer-Shofty et al. (2013) test the effects of intranasal oxytocin administration on fear recognition in schizophrenic patients compared to healthy controls. Finally, Sauer et al. (2013) describe an imaging genomics approach using intranasal oxytocin administration during responses to social stimuli. Specifically, they investigate interactions between oxytocin and dopamine-related genes in contributing to individual differences in the activation of different brain regions. Understanding social behavior in our species is not only clinically extremely relevant for disorders characterized by dysfunctional social relationships, but also research on human social hormones has important implications beyond the clinic. Revealing the biological roots of human social behavior impacts the Social Sciences, including economics, sociology and psychology and moreover, is of great interest to the public at large.

Oxytocin and social pretreatment have similar effects on processing of negative emotional faces in healthy adult males

Oxytocin has been shown to affect several aspects of human social cognition, including facial emotion processing. There is also evidence that social stimuli (such as eye-contact) can effectively modulate endogenous oxytocin levels. In the present study we directly tested whether intranasal oxytocin administration and pre-treatment with social stimuli had similar effects on face processing at the behavioral level. Subjects (N = 52 healthy adult males) were presented with a set of faces with expressions of different valence (negative, neutral, positive) following different types of pretreatment (oxytocin—OT or placebo—PL and social interaction—Soc or no social interaction—NSoc, N = 13 in each) and were asked to rate all faces for perceived emotion and trustworthiness. On the next day subjects' recognition memory was tested on a set of neutral faces and additionally they had to again rate each face for trustworthiness and emotion. Subjects in both the OT and the Soc pretreatment group (as compared to the PL and to the NSoc groups) gave higher emotion and trustworthiness scores for faces with negative emotional expression. Moreover, 24 h later, subjects in the OT and Soc groups (unlike in control groups) gave lower trustworthiness scores for previously negative faces, than for faces previously seen as emotionally neutral or positive. In sum these results provide the first direct evidence of the similar effects of intranasal oxytocin administration and social stimulation on the perception of negative facial emotions as well as on the delayed recall of negative emotional information.

Oxytocin differentially modulates eye gaze to naturalistic social signals of happiness and anger

A number of previous studies has shown that oxytocin (OT) promotes facial emotion recognition and enhances eye gaze to facial stimuli in humans. Other studies report valence-specific effects of OT, supporting the proposed prosocial role of OT in social interactions. In the present study, we tested the hypothesis whether OT might selectively enhance eye gaze to positive, approach-related, but not to negative, threat-related social cues. In a placebo-controlled, double-blind, between-subject design, we assessed the effects of intranasal OT administration (24 IU) in 62 healthy male volunteers on eye gaze toward the eyes of neutral, positive (happy) and negative (angry) facial expressions compared with placebo. In order to capture the dynamics of facial expressions, we used video sequences showing neutral faces gradually displaying a specific emotion. In line with previous studies, OT increased eye gaze toward neutral facial expressions. Moreover, under OT treatment, eye gaze remained increased when the face showed a happy facial expression, but in contrast decreased when the face displayed an angry expression. These results support the notion that OT differentially modulates visual attention toward social signals of positive approach and threat and thereby contributes to the modulation of non-verbal interpersonal communication.

The other side of the coin: oxytocin decreases the adherence to fairness norms.

Oxytocin (OXT) has been implicated in prosocial behaviors such as trust and generosity. Yet, these effects appear to strongly depend on characteristics of the situation and the people with whom we interact or make decisions. Norms and rules can facilitate and guide our actions, with fairness being a particularly salient and fundamental norm. The current study investigated the effects of intranasal OXT administration on fairness considerations in social decision-making in a double-blind, placebo-controlled within-subject design. After having received 24 IU of OXT or placebo (PLC), participants completed a one-shot Dictator Game (DG) and played the role of the responder in a modified version of the Ultimatum Game (UG), in which an unfair offer of eight coins for the proposer and two coins for the responder is paired with either a fair-(5:5) or no-alternative (8:2). Rejection rates were higher when a fair alternative had been available than when there was no alternative to an unfair offer. Importantly, OXT did not de-or increase rejection rates overall, but reduced the sensitivity to contextual fairness, i.e., the context of alternatives in which an offer was made. As dictators, participants allocated less coins to the recipient when given OXT than when given PLC, indicating a decline in generosity. These results suggest that OXT decreases the adherence to fairness norms in social settings where others are likely to be perceived as not belonging to one's ingroup. While our findings do not support the prosocial conception of OXT, they corroborate recent ideas that the effects of OXT are more nuanced than assumed in the past.

Oxytocin decreases handgrip force in reaction to infant crying in females without harsh parenting experiences

Infant crying can elicit sensitive caregiving as well as hostility and harsh parenting responses. In the current study (N = 42 females) with a double-blind experimental design, we tested the effect of intranasal oxytocin administration on the use of excessive force using a hand-grip dynamometer during listening to infant cry sounds. Participants' experiences with harsh parental discipline during childhood were found to moderate the effect of oxytocin administration on the use of excessive force. Participants' whose parents did not discipline them harshly used less excessive force in the oxytocin condition, but for participants who were disciplined harshly there was no difference between the oxytocin and placebo condition. Such effects were not found during listening to infant laughter. We conclude that early caregiving experiences constitute an important moderator of the prosocial and/or stress-reducing effects of oxytocin. Oxytocin administration may increase trust and cooperation in individuals with supportive backgrounds, but not generate this effect in individuals who as a consequence of unfavorable early caregiving experiences may have a bias toward negative interpretation of social cues.

A sniff of trust: Meta-analysis of the effects of intranasal oxytocin administration on face recognition, trust to in-group, and trust to out-group

The neuropeptide oxytocin has a popular reputation of being the 'love' hormone. Here we test meta-analytically whether experiments with intranasal administration of oxytocin provide support for the proposed effects of oxytocin. Three psychological effects were subjected to meta-analysis: facial emotion recognition (13 effect sizes, N=408), in-group trust (8 effect sizes, N=317), and out-group trust (10 effect sizes; N=505). We found that intranasal oxytocin administration enhances the recognition of facial expressions of emotions, and that it elevates the level of in-group trust. The hypothesis that out-group trust is significantly decreased in the oxytocin condition was not supported. It is concluded that a sniff of oxytocin can change emotion perception and behavior in trusting relationships.

The acute effects of intranasal oxytocin administration on endocrine and sexual function in males

The role of the neuropeptide oxytocin (OT) ranges from the modulation of neuroendocrine physiological effects to the establishment of complex social and bonding behaviours. Experimental studies in animals, as well as case reports in humans, suggest that OT affects different aspects of sexual behaviour and has predominantly facilitating properties for sexual appetence and performance. Using a previously established experimental paradigm of sexual arousal and masturbation-induced orgasm, this study investigated the acute effects of intranasal OT application (24I.U.) on endocrine parameters and measures of sexual appetence and function in healthy men (n=10). In a double-blind, placebo-controlled, balanced cross-over design, sexual arousal, and orgasm were induced by an erotic film and masturbation. In addition to the continuous recording of endocrine (OT, cortisol, prolactin, epinephrine, norepinephrine) and cardiovascular data (heart rate), parameters of appetitive, consummatory, and refractory sexual behaviour were assessed using the acute sexual experience scale (ASES). OT plasma levels were significantly elevated after intranasal OT throughout the whole experiment (>60 min). In addition, OT treatment induced significantly higher increases in epinephrine plasma levels during sexual activity without affecting cortisol levels, prolactin levels or heart rate. OT treatment did not alter appetitive, consummatory, and refractory sexual behaviour according to the ASES. However, when subjects were asked about their subjective perception of whether OT or placebo had been applied, eight out of 10 subjects in the OT group answered correctly, thus pointing to an altered perception of arousal. In conclusion, intranasally administered OT leads to a marked increase in OT plasma levels together with increased secretion of catecholamines when subjects are engaged in sexual activity in a laboratory setting. As the effects of OT on sexual behaviour were equivocal, future studies should examine possible facilitating effects further by including males, females, and couples in a field setting, taking into account that OT exerts the most prominent behavioural effects in pair bond formations.