Oxytocin increases emotional theory of mind, but only for low socioeconomic status individuals.
ABSTRACT: 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.
Project description:The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin's dose-response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequence of single-dose sessions, 17 male adults with ASD received 8 international units (IU) oxytocin, 24IU oxytocin or placebo followed by four social-cognitive tasks. We observed an omnibus main effect of treatment on the primary outcome measure of overt emotion salience as measured by emotional ratings of faces (?2=0.18). Compared to placebo, 8IU treatment increased overt emotion salience (P=0.02, d=0.63). There was no statistically significant increase after 24IU treatment (P=0.12, d=0.4). The effects after 8IU oxytocin were observed despite no significant increase in peripheral blood plasma oxytocin concentrations. We found no significant effects for reading the mind in the eyes task performance or secondary outcome social-cognitive tasks (emotional dot probe and face-morphing). To our knowledge, this is the first trial to assess the dose-dependent effects of a single oxytocin administration in autism, with results indicating that a low dose of oxytocin can significantly modulate overt emotion salience despite minimal systemic exposure.
Project description:Background:The neuropeptide oxytocin can extensively modulate human social behavior and affective processing, and its effects can be interpreted in terms of mediating approach-avoidance motivational processes. However, little is known about how oxytocin mediates approach-avoidance behavior and particularly the underlying neural mechanisms. Methods:In a randomized, double-blind, between-subject design, the present pharmaco-fMRI study used an approach-avoidance paradigm to investigate oxytocin's effects on approach-avoidance behavior and associated neural mechanisms. Results:Results revealed that oxytocin generally decreased activity in the right striatum irrespective of response (approach/avoidance) and social context, suggesting an inhibitory effect on motivational representation during both appetitive approach and aversive avoidance. Importantly, while on the behavioral level oxytocin selectively enhanced accuracy when approaching social positive stimuli, on the neural level it decreased left ventral and right dorsal anterior insula activity in response to social vs nonsocial positive stimuli compared with the placebo treatment. The left ventral anterior insula activity was negatively correlated with the corresponding accuracy difference scores in the oxytocin but not in the placebo group. Conclusion:Given the role of the ventral anterior insula in emotional processing and the dorsal anterior insula in salience processing, the oxytocin-induced suppression of activity in these regions may indicate that oxytocin is acting to reduce interference from hyper-activity in core regions of the emotional and salience networks when approaching salient positive social stimuli and thereby to promote social interaction. Thus, oxytocin may be of potential therapeutic benefit for psychiatric disorders exhibiting avoidance of social stimuli.
Project description:Social cognition is impaired in people with schizophrenia and these deficits are strongly correlated with social functioning. Oxytocin is a hypothalamic peptide that contributes to maternal infant bonding and has diverse pro-social effects in adults. This study tested the hypothesis that 12weeks of intranasal oxytocin will improve social cognitive function in outpatients with schizophrenia and schizoaffective disorder. Sixty-eight eligible participants were randomized to oxytocin (24IU twice daily) or placebo. Social cognitive function was assessed using the Emotion Recognition-40, Brüne Theory of Mind, Reading the Mind in the Eyes test, Trustworthiness task and Ambiguous Intentions Hostility Questionnaire at baseline, 6weeks and 12weeks. In addition, social function was assessed using the Specific Levels of Functioning Scale and a role-play test, and psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Fifty-five participants completed the 12-week trial. The study found no evidence for a differential advantage of oxytocin over placebo on social cognition. Among secondary outcomes, there was a modest advantage for oxytocin over placebo on a component of social functioning, although there was also evidence that the placebo group outperformed the oxytocin group on the role-play task. No between-group differences emerged on measures of psychopathology in pre-specified comparisons, but oxytocin showed significant within-group reduction in PANSS negative symptoms and significant between-group improvement in negative symptoms in the schizophrenia subgroup. Further testing is needed to clarify whether oxytocin has therapeutic potential for social cognitive deficits and/or negative symptoms in people with schizophrenia.
Project description:BACKGROUND: The findings of the few studies that have to date investigated the way in which individuals with Anorexia Nervosa (AN) navigate their social environment are somewhat contradictory. We undertook this study to shed new light on the social-cognitive profile of patients with AN, analysing Theory of Mind and emotional functioning. Starting from previous evidence on the role of the amygdala in the neurobiology of AN and in the social cognition, we hypothesise preserved Theory of Mind and impaired emotional functioning in patients with AN. METHODOLOGY: Thirty women diagnosed with AN and thirty-two women matched for education and age were involved in the study. Theory of Mind and emotional functioning were assessed with a set of validated experimental tasks. A measure of perceived social support was also used to test the correlations between this dimension and the social-cognitive profile of AN patients. PRINCIPAL FINDINGS: The performance of patients with AN is significantly worse than that of healthy controls on tasks assessing emotional functioning, whereas patients' performance is comparable to that of healthy controls on the Theory of Mind task. Correlation analyses showed no relationship between scores on any of the social-cognition tasks and either age of onset or duration of illness. A correlation between social support and emotional functioning was found. This latter result seems to suggest a potential role of social support in the treatment and recovery of AN. CONCLUSIONS: The pattern of results followed the experimental hypothesis. They may be useful to help us better understand the social-cognitive profile of patients with AN and to contribute to the development of effective interventions based on the ways in which patients with AN actually perceive their social environment.
Project description:A central assumption that underpins much of the discussion of the role played by social cognition in brain evolution is that social cognition is unusually cognitively demanding. This assumption has never been tested. Here, we use a task in which participants read stories and then answered questions about the stories in a behavioural experiment (39 participants) and an fMRI experiment (17 participants) to show that mentalising requires more time for responses than factual memory of a matched complexity and also that higher orders of mentalising are disproportionately more demanding and require the recruitment of more neurons in brain regions known to be associated with theory of mind, including insula, posterior STS, temporal pole and cerebellum. These results have significant implications both for models of brain function and for models of brain evolution.
Project description:Receiving negative social feedback can be detrimental to emotional, cognitive, and physical well-being, and fear of negative social feedback is a prominent feature of mental illnesses that involve social anxiety. A large body of evidence has implicated the neuropeptides oxytocin and vasopressin in the modulation of human neural activity underlying social cognition, including negative emotion processing; however, the influence of oxytocin and vasopressin on neural activity elicited during negative social evaluation remains unknown. Here 21 healthy men underwent functional magnetic resonance imaging in a double-blind, placebo-controlled, crossover design to determine how intranasally administered oxytocin and vasopressin modulated neural activity when receiving negative feedback on task performance from a study investigator. We found that under placebo, a preferential response to negative social feedback compared with positive social feedback was evoked in brain regions putatively involved in theory of mind (temporoparietal junction), pain processing (anterior insula and supplementary motor area), and identification of emotionally important visual cues in social perception (right fusiform). These activations weakened with oxytocin and vasopressin administration such that neural responses to receiving negative social feedback were not significantly greater than positive social feedback. Our results show effects of both oxytocin and vasopressin on the brain network involved in negative social feedback, informing the possible use of a pharmacological approach targeting these regions in multiple disorders with impairments in social information processing.
Project description:The neurotransmitter oxytocin plays an important role in social affiliation. Low oxytocin levels and defects in the oxytocin receptor have been reported in childhood autism. However, little is known about oxytocin's post-receptor signaling pathways in autism. Oxytocin signals via stimulatory and inhibitory G proteins. c-fos mRNA expression has been used as a marker of OT signaling as well as of G protein signaling. Herein, we hypothesized that oxytocin and its signaling pathways would be altered in children with autism. We measured plasma oxytocin levels by ELISA, G-protein and c-fos mRNA by PCR, and G proteins by immunoblot in cultured peripheral blood mononuclear cells (PBMCs) in children with autism and in age-matched controls. Males with autism displayed elevated oxytocin levels compared to controls (p<0.05). Children with autism displayed significantly higher mRNA for stimulatory G proteins compared to controls (p<0.05). Oxytocin levels correlated strongly positively with c-fos mRNA levels, but only in control participants (p<0.01). Oxytocin, G-protein, and c-fos mRNA levels correlated inversely with measures of social and emotional behaviors, but only in control participants. These data suggest that children with autism may exhibit a dysregulation in oxytocin and/or its signaling pathways.
Project description:RATIONALE:Oxytocin is a neuropeptide widely recognized for its role in regulating social and reproductive behavior. Increasing evidence from animal models suggests that oxytocin also modulates reward circuitry in non-social contexts, but evidence in humans is lacking. OBJECTIVES:We examined the effects of oxytocin administration on reward circuit function in 18 healthy men as they performed a monetary incentive task. METHODS:The blood oxygenation level-dependent (BOLD) signal was measured using functional magnetic resonance imaging in the context of a randomized, double-blind, placebo-controlled, crossover trial of intranasal oxytocin. RESULTS:We found that oxytocin increases the BOLD signal in the midbrain (substantia nigra and ventral tegmental area) during the late phase of the hemodynamic response to incentive stimuli. Oxytocin's effects on midbrain responses correlated positively with its effects on positive emotional state. We did not detect an effect of oxytocin on responses in the nucleus accumbens. Whole-brain analyses revealed that oxytocin attenuated medial prefrontal cortical deactivation specifically during anticipation of loss. CONCLUSIONS:Our findings demonstrate that intranasal administration of oxytocin modulates human midbrain and medial prefrontal function during motivated behavior. These findings suggest that endogenous oxytocin is a neurochemical mediator of reward behaviors in humans-even in a non-social context-and that the oxytocinergic system is a potential target of pharmacotherapy for psychiatric disorders that involve dysfunction of reward circuitry.
Project description:Oxytocin is a key modulator of social interaction, but we possess little knowledge of its underlying effects on neuropsychological processes. We used a spatio-temporal EEG microstates analysis to reveal oxytocin's effects on the temporal dynamics of intrinsically generated activity in neural networks. Given oxytocin's known anxiolytic effects, we hypothesized that it increases the temporal stability of the four archetypal EEG resting networks. Eighty-six male participants had received oxytocin or placebo intranasally before we recorded their resting EEG. As hypothesized, oxytocin globally increased the average duration of the four archetypal resting networks and specifically decreased the occurrence and coverage of an autonomic processing-related network to benefit greater coverage of an attention-related network. Moreover, these neurophysiological changes were more pronounced in participants with high anxiety levels and strong subjectively experienced effects of the oxytocin administration. In sum, our study shows that oxytocin reduces rapid switching among neural resting networks by increasing their temporal stability. Specifically, it seems to reduce the brain's need for preparing the internally-oriented processing of autonomic information, thus enabling the externally-oriented processing of social information. Changes in the temporal dynamics of resting networks might underlie oxytocin's anxiolytic effects - potentially informing innovative psychobiological treatment strategies.
Project description:BACKGROUND:Blunted facial affect is a common negative symptom of schizophrenia. Additionally, assessing the trustworthiness of faces is a social cognitive ability that is impaired in schizophrenia. Currently available pharmacological agents are ineffective at improving either of these symptoms, despite their clinical significance. The hypothalamic neuropeptide oxytocin has multiple prosocial effects when administered intranasally to healthy individuals and shows promise in decreasing negative symptoms and enhancing social cognition in schizophrenia. Although two small studies have investigated oxytocin's effects on ratings of facial trustworthiness in schizophrenia, its effects on facial expressivity have not been investigated in any population. METHOD:We investigated the effects of oxytocin on facial emotional expressivity while participants performed a facial trustworthiness rating task in 33 individuals with schizophrenia and 35 age-matched healthy controls using a double-blind, placebo-controlled, cross-over design. Participants rated the trustworthiness of presented faces interspersed with emotionally evocative photographs while being video-recorded. Participants' facial expressivity in these videos was quantified by blind raters using a well-validated manualized approach (i.e. the Facial Expression Coding System; FACES). RESULTS:While oxytocin administration did not affect ratings of facial trustworthiness, it significantly increased facial expressivity in individuals with schizophrenia (Z = -2.33, p = 0.02) and at trend level in healthy controls (Z = -1.87, p = 0.06). CONCLUSIONS:These results demonstrate that oxytocin administration can increase facial expressivity in response to emotional stimuli and suggest that oxytocin may have the potential to serve as a treatment for blunted facial affect in schizophrenia.