Intranasal Oxytocin Administration Research Articles

ODP576 A pilot randomized clinical trial of intranasal oxytocin to promote weight loss in children, adolescents, and adults with hypothalamic obesity

Abstract Many individuals with brain tumors affecting the hypothalamus and pituitary gain weight excessively after tumor treatment. There is currently no FDA-approved treatment for this condition, which is called hypothalamic obesity. In animals and in some preliminary studies in humans, the hypothalamic hormone oxytocin impacts metabolism, and may be deficient in individuals with hypothalamic obesity. Therefore, we performed a randomized, double-blind, placebo-controlled, cross-over trial to test the effects of 8 weeks of intranasal administration of oxytocin as compared to placebo on body weight in children, adolescents, and young adults (ages 10-<35y) with excess weight gain related to hypothalamic/pituitary brain tumors (N=13). We did not detect an effect of oxytocin on body weight or other metabolic measures. Overall oxytocin appeared well-tolerated, with most side effects being mild and not different from placebo. Our pilot study yielded several other lessons. First, affected individuals have many other medical problems. Also, individuals with hypothalamic obesity also differ from each other with respect to factors that impact body weight (e. g., appetite and eating behavior) and thus future larger studies could test different individualized dosing strategies, combination therapies, and a wider scope of outcomes to examine further the potential value of oxytocin treatment in this disorder. Keywords: Craniopharyngioma, Hypothalamic Dysfunction, Hypothalamus, Obesity, Weight Loss. Presentation: No date and time listed

Oro-mucosal administration of oxytocin using medicated lollipops alters social attention, similar to intranasal and lingual routes: Implications for therapeutic use.

A key functional effect of intranasal administration of the neuropeptide oxytocin is on top-down control of social attention. However, an oro-mucosal administration route may be better tolerated for chronic therapeutic use and evidence suggests that some functional effects of oxytocin can be mediated via peripheral routes. The current study investigated if oxytocin administered orally using medicated lollipops can both increase blood oxytocin concentrations and influence social attention and state anxiety. In a randomized, double-blind, clinical trial adult male participants received oral oxytocin (24IU) or placebo 30-min before completing a well-established anti-saccade paradigm which can assess treatment effects on both top-down and bottom-up attention. Oxytocin administration modulated top-down social attentional processing by increasing anti-saccade error rates on both social and non-social stimuli although it only increased response latencies for social cues. Anti-saccade errors were also positively associated with the proportionate increase in plasma oxytocin concentrations. A comparison analysis showed that oral oxytocin administration increased blood concentrations to a similar degree as given by lingual spray, although less than when given intranasally. Importantly, attentional and anxiolytic effects of oxytocin in the anti-saccade task were similar across intranasal, lingual, and oral administration routes. These findings demonstrate that oral administration of oxytocin, similar to via intranasal and lingual routes, can modulate top-down social attention and state anxiety and support its potential for therapeutic use. They also provide further evidence that functional effects of exogenously administered oxytocin can be mediated indirectly either by crossing the blood brain barrier or producing receptor mediated vagal stimulation, as opposed to via direct entry into the brain.

Effects of single- and multiple-dose oxytocin treatment on amygdala low-frequency BOLD fluctuations and BOLD spectral dynamics in autism

Prior neuroimaging clinical trials investigating the neural effects of intranasal administration of the neuropeptide oxytocin demonstrated a key role of the amygdala in oxytocin’s neuromodulatory effects. These studies mostly demonstrated the acute effects of single-dose administrations, examining task-dependent effects of oxytocin on brain activity elicited during explicit experimental tasks or stimuli presentations. The increased consideration of oxytocin as a potential ameliorating treatment in autism spectrum disorder (ASD) requires a better understanding of how multiple-dose oxytocin administration affects intrinsic, task-free, amygdala function. In this double-blind, randomized, placebo-controlled trial with between-subject design, 38 adult men with ASD underwent resting-state fMRI scanning before and after oxytocin or placebo treatment. Effects were assessed either after a single-dose administration, consisting of 24 international units, or after multiple-dose treatment, consisting of 4 weeks of once-daily nasal spray administrations. Compared to placebo, oxytocin induced a decrease in intrinsic resting-state BOLD signal amplitudes of the bilateral amygdala (fractional amplitudes of low-frequency fluctuations) and modulated cross-frequency interactions between adjacent BOLD frequency components. The right amygdala showed a pattern of reduced cross-frequency harmonicity, while the left amygdala showed a relative increase in harmonic cross-frequency interactions after oxytocin treatment. Notably, the direction and magnitude of BOLD spectral changes induced after a single-dose were qualitatively similar to treatment effects induced after multiple-dose treatment. Furthermore, the identified spectral changes in amygdalar BOLD amplitude and cross-frequency harmonicity were associated with improved feelings of tension, reflecting oxytocin’s anxiolytic, stress-reducing neuromodulatory role. The observed effects of oxytocin on amygdalar BOLD spectral characteristics and associated behaviors contribute to a deeper mechanistic understanding of the intrinsic, task-free neuromodulatory dynamics that underlie single- and multiple-dose oxytocin treatment in ASD. European Clinical Trial Registry (Eudract 2014-000586-45).

Frequency-Tagging EEG of Superimposed Social and Non-Social Visual Stimulation Streams Provides No Support for Social Salience Enhancement after Intranasal Oxytocin Administration.

The social salience hypothesis proposes that the neuropeptide oxytocin (OT) can impact human social behavior by modulating the salience of social cues. Here, frequency-tagging EEG was used to quantify the neural responses to social versus non-social stimuli while administering a single dose of OT (24 IU) versus placebo treatment. Specifically, two streams of faces and houses were superimposed on one another, with each stream of stimuli tagged with a particular presentation rate (i.e., 6 and 7.5 Hz or vice versa). These distinctive frequency tags allowed unambiguously disentangling and objectively quantifying the respective neural responses elicited by the different streams of stimuli. This study involved a double-blind, placebo-controlled, cross-over trial with 31 healthy adult men. Based on four trials of 60 s, we detected robust frequency-tagged neural responses in each individual, with entrainment to faces being more pronounced in lateral occipito-temporal regions and entrainment to houses being focused in medial occipital regions. However, contrary to our expectation, a single dose of OT did not modulate these stimulus-driven neural responses, not in terms of enhanced social processing nor in terms of generally enhanced information salience. Bayesian analyses formally confirmed these null findings. Possibly, the baseline ceiling level performance of these neurotypical adult participants as well as the personal irrelevance of the applied stimulation streams might have hindered the observation of any OT effect.

A randomized, double-blind, placebo-controlled clinical trial of 8-week intranasal oxytocin administration in adults with obesity: Rationale, study design, and methods

BackgroundObesity affects more than one-third of adults in the U.S., and effective treatment options are urgently needed. Oxytocin administration induces weight loss in animal models of obesity via effects on caloric intake, energy expenditure, and fat metabolism. We study intranasal oxytocin, an investigational drug shown to reduce caloric intake in humans, as a potential novel treatment for obesity. MethodsWe report the rationale, design, methods, and biostatistical analysis plan of a randomized, double-blind, placebo-controlled clinical trial of intranasal oxytocin for weight loss (primary endpoint) in adults with obesity. Participants (aged 18–45 years) were randomly allocated (1:1) to oxytocin (four times daily over eight weeks) versus placebo. Randomization was stratified by biological sex and BMI (30 to <35, 35 to <40, ≥40 kg/m2). We investigate the efficacy, safety, and mechanisms of oxytocin administration in reducing body weight. Secondary endpoints include changes in resting energy expenditure, body composition, caloric intake, metabolic profile, and brain activation via functional magnetic resonance imaging in response to food images and during an impulse control task. Safety and tolerability (e.g., review of adverse events, vital signs, electrocardiogram, comprehensive metabolic panel) are assessed throughout the study and six weeks after treatment completion. ResultsSixty-one male and female participants aged 18–45 years were randomized (mean age 34 years, mean BMI 37 kg/m2). The study sample is diverse with 38% identifying as non-White and 20% Hispanic. ConclusionInvestigating intranasal oxytocin's efficacy, safety, and mechanisms as an anti-obesity medication will advance the search for optimal treatment strategies for obesity and its associated severe sequelae.

Oxytocin-a social peptide? Deconstructing the evidence.

In this paper, we analyse the claim that oxytocin is a ‘social neuropeptide’. This claim originated from evidence that oxytocin was instrumental in the initiation of maternal behaviour and it was extended to become the claim that oxytocin has a key role in promoting social interactions between individuals. We begin by considering the structure of the scientific literature on this topic, identifying closely interconnected clusters of papers on particular themes. We then analyse this claim by considering evidence of four types as generated by these clusters: (i) mechanistic studies in animal models, designed to understand the pathways involved in the behavioural effects of centrally administered oxytocin; (ii) evidence from observational studies indicating an association between oxytocin signalling pathways and social behaviour; (iii) evidence from intervention studies, mainly involving intranasal oxytocin administration; and (iv) evidence from translational studies of patients with disorders of social behaviour. We then critically analyse the most highly cited papers in each segment of the evidence; we conclude that, if these represent the best evidence, then the evidence for the claim is weak.This article is part of the theme issue ‘Interplays between oxytocin and other neuromodulators in shaping complex social behaviours’.

Oxytocin administration versus emotion training in healthy males: considerations for future research.

Identifying emotions correctly is essential for successful social interaction. There is therefore a keen interest in designing therapeutic interventions to improve emotion recognition in individuals who struggle with social interaction. The neuropeptide oxytocin has been proposed as a potential physiological intervention due to its important role in emotion recognition and other aspects of social cognition. However, there are a number of caveats to consider with the current form of intranasal oxytocin commonly used in the literature. Psychological interventions, on the other hand, do not carry the same caveats, and there is, therefore, a need to understand how intranasal oxytocin administration compares to psychological interventions designed to target the same psychological phenomena; and whether a combined intervention approach may provide additive benefits. Here we present a pilot, proof-of-concept study in healthy volunteers comparing the effect of intranasal oxytocin against a validated emotion training programme, finding that the psychological intervention, and not intranasal oxytocin, improved emotion recognition specifically for angry expressions. We discuss the theoretical implications of the research for future clinical trials. This article is part of the theme issue 'Interplays between oxytocin and other neuromodulators in shaping complex social behaviours'.

Progress in Personalized Psychiatric Therapy with the Example of Using Intranasal Oxytocin in PTSD Treatment.

Post-traumatic stress disorder (PTSD) is a severe mental disorder that results in the frequent coexistence of other diseases, lowers patients’ quality of life, and has a high annual cost of treatment. However, despite the variety of therapeutic approaches that exist, some patients still do not achieve the desired results. In addition, we may soon face an increase in the number of new PTSD cases because of the current global situation—both the COVID-19 pandemic and the ongoing armed conflicts. Hence, in recent years, many publications have sought a new, more personalized treatment approach. One such approach is the administration of intranasal oxytocin (INOXT), which, due to its pleiotropic effects, seems to be a promising therapeutic option. However, the current findings suggest that it might only be helpful for a limited, strictly selected group of patients.

Oxytocin Impairs the Recognition of Micro-Expressions of Surprise and Disgust.

As fleeting facial expressions which reveal the emotion that a person tries to conceal, micro-expressions have great application potentials for fields like security, national defense and medical treatment. However, the physiological basis for the recognition of these facial expressions is poorly understood. In the present research, we utilized a double-blind, placebo-controlled, mixed-model experimental design to investigate the effects of oxytocin on the recognition of micro-expressions in three behavioral studies. Specifically, in Studies 1 and 2, participants were asked to perform a laboratory-based standardized micro-expression recognition task after self-administration of a single dose of intranasal oxytocin (40 IU) or placebo (containing all ingredients except for the neuropeptide). In Study 3, we further examined the effects of oxytocin on the recognition of natural micro-expressions. The results showed that intranasal oxytocin decreased the recognition speed for standardized intense micro-expressions of surprise (Study 1) and decreased the recognition accuracy for standardized subtle micro-expressions of disgust (Study 2). The results of Study 3 further revealed that intranasal oxytocin administration significantly reduced the recognition accuracy for natural micro-expressions of surprise and disgust. The present research is the first to investigate the effects of oxytocin on micro-expression recognition. It suggests that the oxytocin mainly plays an inhibiting role in the recognition of micro-expressions and there are fundamental differences in the neurophysiological basis for the recognition of micro-expressions and macro-expressions.

Age-Related Differences in Amygdala Activation Associated With Face Trustworthiness but No Evidence of Oxytocin Modulation.

The amygdala has been shown to be responsive to face trustworthiness. While older adults typically give higher face trustworthiness ratings than young adults, a direct link between amygdala response and age-related differences in face trustworthiness evaluation has not yet been confirmed. Additionally, there is a possible modulatory role of the neuropeptide oxytocin in face trustworthiness evaluation, but the results are mixed and effects unexplored in aging. To address these research gaps, young, and older adults were randomly assigned to oxytocin or placebo self-administration via a nasal spray before rating faces on trustworthiness while undergoing functional magnetic resonance imaging. There was no overall age-group difference in face trustworthiness ratings, but older compared to young participants gave higher trustworthiness ratings to ambivalently untrustworthy-looking faces. In both age groups, lower face trustworthiness ratings were associated with higher left amygdala activity. A comparable negative linear association was observed in right amygdala but only among young participants. Also, in the right amygdala, lower and higher, compared to moderate, face trustworthiness ratings were associated with greater right amygdala activity (i.e., positive quadratic (U-shaped) association) for both age groups. Neither the behavioral nor the brain effects were modulated by a single dose of intranasal oxytocin administration, however. These results suggest dampened response to faces with lower trustworthiness among older compared to young adults, supporting the notion of reduced sensitivity to cues of untrustworthiness in aging. The findings also extend evidence of an age-related positivity effect to the evaluation of face trustworthiness.

Protective Effects of Intranasally Administrated Oxytocin-Loaded Nanoparticles on Pentylenetetrazole-Kindling Epilepsy in Terms of Seizure Severity, Memory, Neurogenesis, and Neuronal Damage.

Pentylenetetrazole (PTZ)-induced kindling is an animal model for studying human temporal lobe epilepsy (TLE), which is characterized by alterations of hippocampal neurons and memory. Although the intranasal (IN) administration of oxytocin (OT) has limited efficiency, nanoparticles (NPs) are a promising candidate to deliver OT to the brain. However, there are very limited data on epilepsy research about oxytocin-loaded nanoparticles (NP-OTs). The aim of this study is to investigate the effects of IN administration of chronic NP-OTs on the hippocampus of PTZ-induced male epileptic rats in terms of seizure severity, memory, neurogenesis, and neuronal damage. Saline/OT/NP-OTs were administrated to both control (Ctrl) and PTZ groups intranasally. Consequently, saline and PTZ were injected, respectively, 25 times every 48 h. Then, seizure severity (score and latency) was calculated for the PTZ groups. A spatial working memory evaluation test (SWMET) was performed after the last injection. Hippocampus histopathology, neurogenesis, and apoptosis were demonstrated. Serum total antioxidant status (TAS) and total oxidant status (TOS) levels and the oxidative stress index (OSI) were measured. We showed that OTs and NP-OTs prevented the kindling development and had positive effects on seizure severity. SWMET-related behaviors were also recovered in the PTZ + NP-OT group. A significant increase of neurogenesis and decrease of apoptosis in the hippocampus of the PTZ + NP-OT group were observed, while OTs and NP-OTs had protective effects against PTZ-induced damage to hippocampal neurons. Our results indicate that the chronic administration of NP-OTs may have positive effects on hippocampal damage via increasing neurogenesis and decreasing apoptosis and seizure severity.

Intranasal oxytocin studies on dogs might not be double-blind

A single dose of intranasal oxytocin has been shown to affect family dogs’ behaviour across a series of social tasks and situations. These studies have all been conducted using a double-blind placebo controlled design, which is the gold-standard in the field of drug-effect research. However, it has not been investigated whether intranasal oxytocin studies in dogs are truly double-blind, meaning that participants are indeed unaware of the treatment(s) dogs have received. Here we used unpublished data from three already published studies assessing the effects of intranasal oxytocin (compared to placebo) administration on dogs’ behaviour. Owners in these studies were asked in the end to make a guess about the treatment received, which is analysed in the present paper. Results show that in two out of the three datasets owners were above chance with their guesses when dogs had received placebo treatment; and in one out of the three datasets they were also overall significantly above chance when looking at data from both the oxytocin and placebo groups. Owners’ guesses were not related to dogs’ performance in the variables measured in any of the three behavioural tasks. These results clearly indicate that caution should be taken regarding the blindness of intranasal oxytocin experiments in dogs. However, we also conclude that the previously reported oxytocin effects on dogs’ behaviour (at least in these three studies) were not caused by the owners’ beliefs.

Impact of Magnesium on Oxytocin Receptor Function.

Simple SummaryWhat is already known: Mg2+ levels modulate the affinity of oxytocin receptors for oxytocin in vitro, low serum Mg2+ is correlated with migraine headache onset. What this study adds: Electrophysiologic and behavioral assays demonstrate that Mg2+ increases the efficacy of oxytocin; oxytocin efficacy is limited by Mg2+ availability. Clinical significance: Modulating Mg2+ levels may enhance oxytocin efficacy for pain, other uses, and endogenous processes.Background and Purpose: The intranasal administration of oxytocin (OT) reduces migraine headaches through activation of the oxytocin receptor (OTR). Magnesium ion (Mg2+) concentration is critical to the activation of the OTR, and a low serum Mg2+ concentration is predictive of a migraine headache. We, therefore, examined the functional impact of Mg2+ concentration on OT-OTR binding efficacy using two complimentary bioassays. Experimental Approach: Current clamp recordings of rat trigeminal ganglia (TG) neurons measured the impact of Mg2+ on an OT-induced reduction in excitability. In addition, we assessed the impact of Mg2+ on intranasal OT-induced craniofacial analgesia in rats. Key Results: While OT alone dose-dependently hyperpolarized TG neurons, decreasing their excitability, the addition of 1.75 mM Mg2+ significantly enhanced this effect. Similarly, while the intranasal application of OT produced dose-dependent craniofacial analgesia, Mg2+ significantly enhanced these effects. Conclusions and Implications: OT efficacy may be limited by low ambient Mg2+ levels. The addition of Mg2+ to OT formulations may improve its efficacy in reducing headache pain as well as for other OT-dependent processes.

Examining the effect of chronic intranasal oxytocin administration on the neuroanatomy and behavior of three autism-related mouse models

Although initially showing great potential, oxytocin treatment has encountered a translational hurdle in its promise of treating the social deficits of autism. Some debate surrounds the ability of oxytocin to successfully enter the brain, and therefore modify neuroanatomy. Moreover, given the heterogeneous nature of autism, treatment will only amerliorate symptoms in a subset of patients. Therefore, to determine whether oxytocin changes brain circuitry, and whether it does so variably, depending on genotype, we implemented a large randomized, blinded, placebo-controlled, preclinical study on chronic intranasal oxytocin treatment in three different mouse models related to autism with a focus on using neuroanatomical phenotypes to assess and subset treatment response. Intranasal oxytocin (0.6IU) was administered daily, for 28 days, starting at 5 weeks of age to the 16p11.2 deletion, Shank3 (exon 4–9) knockout, and Fmr1 knockout mouse models. Given the sensitivity of structural magnetic resonance imaging (MRI) to the neurological effects of interventions like drugs, along with many other advantages, the mice underwent in vivo longitudinal and high-resolution ex vivo imaging with MRI. The scans included three in vivo T1weighted, 90 um isotropic resolution scans and a T2-weighted, 3D fast spin echo with 40um isotropic resolution ex vivo scan to assess the changes in neuroanatomy using established automated image registration and deformation based morphometry approaches in response to oxytocin treatment. The behavior of the mice was assessed in multiple domains, including social behaviours and repetitive behaviours, among others. Treatment effect on the neuroanatomy did not reach significance, although the pattern of trending effects was promising. No significant effect of treatment was found on social behavior in any of the strains, although a significant effect of treatment was found in the Fmr1 mouse, with treatment normalizing a grooming deficit. No other treatment effect on behavior was observed that survived multiple comparisons correction. Overall, chronic treatment with oxytocin had limited effects on the three mouse models related to autism, and no promising pattern of response susceptibility emerged.

Effects of oxytocin and vasopressin administration on human fathers' sensitive and challenging parenting: A randomized within-subject controlled trial

This randomized, double-blind, placebo-controlled within-subject study examined the effects of intranasal administration of oxytocin and vasopressin on fathers' sensitive and challenging parenting behaviors. Furthermore, we examined the moderating role of fathers' early childhood experiences. The sample consisted of 70 fathers with their 2- to 12-month-old infants. All fathers were assigned to each of the three experimental sessions (oxytocin, vasopressin, and placebo), on three separate days, with random order and intervening periods of one to two weeks. Sensitive and challenging parenting behaviors (CPB) were observed during a 10-minute free play task. Results showed no effects of vasopressin administration on paternal sensitivity. Fathers in the oxytocin condition were less sensitive than fathers in the placebo condition, and this effect was moderated by fathers' own childhood experiences: Fathers who reported higher levels of experienced parental love withdrawal were less sensitive in the oxytocin condition as compared to the placebo condition, whereas fathers with less experienced parental love withdrawal showed no difference in sensitivity between the oxytocin and placebo condition. No effects were found of oxytocin and vasopressin administration on fathers' CPB. Our results, although partly unexpected, are largely in line with previous literature showing that oxytocin administration can exert negative effects in individuals with adverse childhood experiences.

Early life oxytocin treatment improves thermo-sensory reactivity and maternal behavior in neonates lacking the autism-associated gene Magel2

Atypical responses to sensory stimuli are considered as a core aspect and early life marker of autism spectrum disorders (ASD). Although recent findings performed in mouse ASD genetic models report sensory deficits, these were explored exclusively during juvenile or adult period. Whether sensory dysfunctions might be present at the early life stage and rescued by therapeutic strategy are fairly uninvestigated. Here we found that under cool environment neonatal mice lacking the autism-associated gene Magel2 present pup calls hypo-reactivity and are retrieved with delay by their wild-type dam. This neonatal atypical sensory reactivity to cool stimuli was not associated with autonomic thermoregulatory alteration but with a deficit of the oxytocinergic system. Indeed, we show in control neonates that pharmacogenetic inactivation of hypothalamic oxytocin neurons mimicked atypical thermosensory reactivity found in Magel2 mutants. Furthermore, pharmacological intranasal administration of oxytocin to Magel2 neonates was able to rescue both the atypical thermosensory response and the maternal pup retrieval. This preclinical study establishes for the first-time early life impairments in thermosensory integration and suggest a therapeutic potential benefit of intranasal oxytocin treatment on neonatal atypical sensory reactivity for autism.

Transcriptome Analysis in Hippocampus of Rats Prenatally Exposed to Valproic Acid and Effects of Intranasal Treatment of Oxytocin.

Autism spectrum disorder (ASD) is a heterogeneous disorder characterized by repetitive behaviors and social impairments, often accompanied by learning disabilities. It has been documented that the neuropeptide oxytocin (OXT) ameliorates core symptoms in patients with ASD. We recently reported that chronic administration of intranasal OXT reversed social and learning impairments in prenatally valproic acid (VPA)-exposed rats. However, the underlying molecular mechanisms remain unclear. Here, we explored molecular alterations in the hippocampus of rats and the effects of chronic administration of intranasal OXT (12 μg/kg/d). Microarray analyses revealed that prenatal VPA exposure altered gene expression, a part of which is suggested as a candidate in ASD and is involved in key features including memory, developmental processes, and epilepsy. OXT partly improved the expression of these genes, which were predicted to interact with those involved in social behaviors and hippocampal-dependent memory. Collectively, the present study documented molecular profiling in the hippocampus related to ASD and improvement by chronic treatment with OXT.

Oxytocin promotes social proximity and decreases vigilance in groups of African lions

SummaryOxytocin modulates mammalian social behavior; however, behavioral responses to intranasal oxytocin can vary across species and contexts. The complexity of social interactions increases with group dynamics, and the impacts of oxytocin on both within- and between-group contexts are unknown. We tested the effects of intranasal administration of oxytocin on social and non-social behaviors within in-group and out-group contexts in African lions. We hypothesized that, post intranasal oxytocin administration, lions would be in closer proximity with fellow group members, whereas out-group stimuli could either produce a heightened vigilance response or an attenuated one. Compared to control trials, post oxytocin administration, lions increased their time spent in close proximity (reducing their distance to the nearest neighbor) and decreased vigilance toward out-group intruders (reducing their vocalizations following a roar-playback). These results not only have important implications for understanding the evolution of social circuitry but may also have practical applications for conservation efforts.

Endogenous oxytocin levels are associated with facial emotion recognition accuracy but not gaze behavior in individuals with schizophrenia.

Difficulties in social cognition are common in individuals with schizophrenia (SZ) and are not ameliorated by antipsychotic treatment. Intranasal oxytocin (OT) administration has been explored as a potential intervention to improve social cognition; however, results are inconsistent, suggesting potential individual difference variables that may influence treatment response. Less is known about the relationship between endogenous OT and social cognition in SZ, knowledge of which may improve the development of OT-focused therapies. We examined plasma OT in relationship to facial emotion recognition and visual attention to salient facial features in SZ and controls. Forty-two individuals with SZ and 23 healthy controls viewed photographs of facial expressions of varying emotional intensity and identified the emotional expression displayed. Participants' gaze behavior during the task was recorded via eye tracking. Plasma oxytocin concentrations were determined by radioimmunoassay. SZ were less accurate than controls at identifying high-intensity fearful facial expressions and low-intensity sad expressions. Lower overall and high-intensity facial emotion recognition accuracy was associated with lower plasma OT levels in SZ but not controls. OT was not associated with visual attention to salient facial features; however, SZ had reduced visual attention to the nose region compared to controls. Individual differences in endogenous OT predict facial emotion recognition ability in SZ but are not associated with visual attention to salient facial features. Increased understanding of the association between endogenous OT and social cognitive abilities in SZ may help improve the design and interpretation of OT-focused clinical trials in SZ.

Reduced vagal activity in borderline personality disorder is unaffected by intranasal oxytocin administration, but predicted by the interaction between childhood trauma and attachment insecurity

Individuals with borderline personality disorder (BPD) show self-regulatory deficits, associated with reduced heart-rate variability (HRV). However, results on reduced HRV in BPD remain heterogeneous, thus encouraging the search for developmental constructs explaining this heterogeneity. The present study first examined predictors of reduced resting-state HRV in BPD, namely the interaction between self-reported adult attachment insecurity and childhood trauma. Second, we investigated if alterations in resting-state HRV are modified by intranasal oxytocin administration, as oxytocin may enhance HRV and is implicated in the interaction between childhood trauma and disturbed attachment for the pathogenesis of BPD. In a randomized, placebo-controlled trial, 53 unmedicated women with BPD and 60 healthy controls (HC) self-administered either 24 I.U. of oxytocin or placebo and underwent a 4-min electrocardiogram. Our results replicate significantly reduced HRV in women with BPD, explained up to 16% by variations in childhood trauma and attachment insecurity. At high levels of acute attachment insecurity, higher levels of childhood trauma significantly predicted reduced HRV in BPD. However, our results do not support a significant effect of oxytocin on mean HRV, and no interaction effect emerged including childhood trauma and attachment insecurity. Our findings highlight a complex interaction between reduced vagal activity and developmental factors in BPD.