Search

Prosocial and moral behaviors have overlapping neural systems and can both be affected in a number of psychiatric disorders, although whether they involve similar neurochemical systems is unclear. In the current registered randomized placebo-controlled trial on 180 adult male and female subjects, we investigated the effects of intranasal administration of oxytocin and vasopressin, which play key roles in influencing social behavior, on moral emotion ratings for situations involving harming others and on judgments of moral dilemmas where others are harmed for a greater good. Oxytocin, but not vasopressin, enhanced feelings of guilt and shame for intentional but not accidental harm and reduced endorsement of intentionally harming others to achieve a greater good. Neither peptide influenced arousal ratings for the scenarios. Effects of oxytocin on guilt and shame were strongest in individuals scoring lower on the personal distress subscale of trait empathy. Overall, findings demonstrate for the first time that oxytocin, but not vasopressin, promotes enhanced feelings of guilt and shame and unwillingness to harm others irrespective of the consequences. This may reflect associations between oxytocin and empathy and vasopressin with aggression and suggests that oxytocin may have greater therapeutic potential for disorders with atypical social and moral behavior., (© 2024. The Author(s).)

This meta-analysis investigates the effect of classic psychedelic drugs on empathy and focuses on cognitive and emotional empathy measured using the Multifaceted Empathy Test (MET). Empathy entails the ability to understand and share the feelings of another and is a significant component of social interaction. Several studies have examined the effects of psychedelic drugs such as LSD, psilocybin and ayahuasca on empathy, yet their overall effect has not been studied so far. In this meta-analysis, we reviewed data from studies up to November 2023 with the aim of examining the effects of various psychedelic drugs on empathic abilities broadly. Our findings suggest that classical psychedelics significantly enhance explicit and implicit emotional empathy without affecting measures of cognitive empathy. The results emphasize the need to continue testing the therapeutic potential of classic psychedelic drugs., (© 2024. The Author(s).)

Out-of-body experiences (OBEs) are subjective phenomena during which individuals feel disembodied or perceive themselves as outside of their physical bodies, often resulting in profound and transformative effects. In particular, experiencers report greater heightened pro-social behavior, including more peaceful relationships, tolerance, and empathy. Drawing parallels with the phenomenon of ego dissolution induced by certain psychedelic substances, we explore the notion that OBEs may engender these changes through ego dissolution, which fosters a deep-seated sense of unity and interconnectedness with others. We then assess potential brain mechanisms underlying the link between OBEs and empathy, considering the involvement of the temporoparietal junction and the Default Mode Network. This manuscript offers an examination of the potential pathways through which OBEs catalyze empathic enhancement, shedding light on the intricate interplay between altered states of consciousness and human empathy., (Copyright © 2024. Published by Elsevier Ltd.)

Administration of low-dose lipopolysaccharide (LPS) to healthy humans is a translational approach to analyze the effects of acute systemic inflammation and sickness behavior. Although studies documented that LPS-induced inflammation can alter social behavior, its impact on empathy remains poorly understood. In this double-blind, placebo-controlled study, 52 healthy female volunteers received an intravenous injection of either LPS (0.4 ng/kg body weight) or placebo and completed the Social Interaction Empathy Task (SIET) two hours after injection. Physiological responses (blood pressure, heart rate, body temperature, cytokines, cortisol) were analyzed along with sickness symptoms and mood before and after LPS or placebo administration. LPS application led to significant increases in plasma cytokines and sickness symptoms as well as low mood. Moreover, volunteers receiving LPS showed significantly less empathy for other's psychological pain than those who received placebo. Furthermore, LPS-injected volunteers with more severe sickness symptoms displayed higher pain ratings in the first-person perspective. Thus, low-grade inflammation reduces empathy for other's psychological pain which might reflect an adaptive strategy to save energy by not responding empathetically when sick oneself., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Methamphetamine (METH, "Crystal Meth") and 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") share structural-chemical similarities but have distinct psychotropic profiles due to specific neurochemical actions. Previous research has suggested that their impact on social cognitive functions and social behaviour may differ significantly, however, direct comparisons of METH and MDMA users regarding social cognition and interaction are lacking. Performances in cognitive and emotional empathy (Multifaceted Empathy Test) and emotion sensitivity (Face Morphing Task), as well as aggressive social behaviour (Competitive Reaction Time Task) were assessed in samples of n = 40 chronic METH users, n = 39 chronic MDMA users and n = 86 stimulant-naïve controls (total N = 165). Self-reports and hair samples were used to obtain subjective and objective estimates of substance use patterns. METH users displayed diminished cognitive and emotional empathy towards positive stimuli, elevated punitive social behaviour regardless of provocation, and self-reported heightened trait anger relative to controls. MDMA users diverged from the control group only by exhibiting a distinct rise in punitive behaviour when faced with provocation. Correlation analyses indicated that both higher hair concentrations of MDMA and METH may be associated with reduced cognitive empathy. Moreover, greater lifetime MDMA use correlated with increased punitive behaviour among MDMA users. Our findings confirm elevated aggression and empathy deficits in chronic METH users, while chronic MDMA users only displayed more impulsive aggression. Dose-response correlations indicate that some of these deficits might be a consequence of use. Specifically, the dopaminergic mechanism of METH might be responsible for social-cognitive deficits., Competing Interests: Declaration of competing interest The authors declare that they do not possess any identifiable conflicting financial interests or personal affiliations that may have exerted influence on the findings presented in this paper., (Copyright © 2024. Published by Elsevier B.V.)

MDMA (3,4-methylenedioxymethamphetamine) is a psychoactive drug with powerful prosocial effects. While MDMA is sometimes termed an "empathogen," empirical studies have struggled to clearly demonstrate these effects or pinpoint underlying mechanisms. Here, we paired the social transfer of pain and analgesia-behavioral tests modeling empathy in mice-with region-specific neuropharmacology, optogenetics, and transgenic manipulations to explore MDMA's action as an empathogen. We report that MDMA, given intraperitoneally or infused directly into the nucleus accumbens (NAc), robustly enhances the social transfer of pain and analgesia. Optogenetic stimulation of 5-HT release in the NAc recapitulates the effects of MDMA, implicating 5-HT signaling as a core mechanism. Last, we demonstrate that systemic MDMA or optogenetic stimulation of NAc 5-HT inputs restores deficits in empathy-like behaviors in the Shank3- deficient mouse model of autism. These findings demonstrate enhancement of empathy-related behaviors by MDMA and implicate 5-HT signaling in the NAc as a core mechanism mediating MDMA's empathogenic effects.

Emotional contagion is the most ancestral form of empathy. We tested to what extent the proximate mechanisms of emotional contagion are evolutionarily conserved by assessing the role of oxytocin, known to regulate empathic behaviors in mammals, in social fear contagion in zebrafish. Using oxytocin and oxytocin receptor mutants, we show that oxytocin is both necessary and sufficient for observer zebrafish to imitate the distressed behavior of conspecific demonstrators. The brain regions associated with emotional contagion in zebrafish are homologous to those involved in the same process in rodents (e.g., striatum, lateral septum), receiving direct projections from oxytocinergic neurons located in the pre-optic area. Together, our results support an evolutionary conserved role for oxytocin as a key regulator of basic empathic behaviors across vertebrates.

3,4-Methylenedioxymethamphetamine (MDMA) is a psychostimulant known for producing positive subjective effects and for enhancing social functioning and social connection in both clinical and recreational settings. Over the past two decades, scientists have begun to study the psychological effects of MDMA through rigorous placebo-controlled experimental work. However, most existing studies have small Ns, and the average sizes of the reported effects are unknown, creating uncertainty about the impact of these findings. The goal of the present study was to quantify the strength of MDMA's effects on self-reported social connection by aggregating sociability-related outcomes across multiple placebo-controlled studies. To this end, we conducted a multilevel meta-analysis based on 27 studies, 54 effect sizes, and a total of 592 participants. The results revealed a moderate-to-large effect (d = 0.86; 95% CI [0.68, 1.04]; r = .39; 95% CI [.32, .46]) of MDMA on self-reported sociability-related outcomes (e.g., feeling loving, talkative, and friendly). Given the magnitude of its effect on felt sociability, we propose that MDMA may have powerful implications for a variety of social contexts and for clinical settings, in particular. Finally, we discuss potential mechanisms underlying the relationship between MDMA and sociability-related feelings, as well as future directions for experimental work in this area., Competing Interests: The authors have declared that no competing interests exist.

Oral contraceptives (OC) and endogenous female sex hormones in naturally cycling women (NC) are related to a wide range of psychological variables (eg, cognition and affect). Little research on social behavior has been done. One study documented a tendency towards more prosocial behavior in NC than OC women, but the underlying neuroendocrine mechanisms remain unknown. The sex hormones progesterone and estradiol are potential candidates. We analyzed social decision-making and social behavior in 83 healthy women (38 OC and 45 NC) via the Social Value Orientation (SVO) and in real social interactions within a paradigm adapted from behavioral economics. We also measured empathy, and collected saliva samples to quantify the basal levels of estradiol and progesterone. Our analyses revealed higher levels of prosocial behavior and emotional empathy in NC than in OC women, a finding supported by higher levels of prosocial decisions in NC than OC women in the SVO. Regarding the underlying biological mechanisms, we detected lower progesterone levels in OC than NC women. Exploratory analyses revealed a negative correlation between progesterone and trust on the trend level. We found no correlations between estradiol and behavior. Our findings provide evidence that OC modulate social behavior and initial indications of a possible modulation by progesterone. Further research is needed to replicate our findings and extend them to other social behaviors., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Reduced empathic abilities are frequently observed in drug abusers. These deficits may compromise interpersonal interactions and contribute to diminished social functioning. However, previous evidence regarding empathy and addiction is behaviorally unspecific and virtually null in terms of their brain structural or functional correlates. Moreover, no previous study has investigated how empathy is affected by drugs whose consumption is particularly characterized by counter-empathic behaviors. Here, we conducted the first assessment of neurocognitive correlates of empathy for pain in dependent users (predominantly men) of smoked cocaine (SC, coca paste, n = 37). We compared their performance in the empathy task with that of two groups matched in relevant demographic variables: 24 dependent users of insufflated cocaine hydrochloride (CC) and 21 healthy controls. In addition, we explored the structural anatomy and functional connectivity (FC) correlates of empathic impairments across groups. Our results showed that, compared to CC and controls, SC users exhibited a selective reduction of empathic concern for intentional harms. These impairments were associated with lower gray matter volumes in regions subserving social cognition (i.e., right inferior parietal lobule, supramarginal and angular gyri). Furthermore, reduced empathic concern correlated with FC within affective empathy and social cognition networks, which are also linked to cognitive changes reported in addiction (i.e., inferior frontal and orbital gyri, posterior insula, supplementary motor area, cingulate cortex). Our findings suggest that chronic consumption of SC may involve reduced empathic concern and relevant neuroanatomical and FC abnormalities, which, in turn, may result in social interaction dysfunction. These results can inform theoretical and applied developments in neuropsychopharmacology., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Evidence suggests that intranasal application of oxytocin facilitates empathy and modulates its underlying neural processes, which are often impaired in individuals with autism spectrum disorders (ASD). Oxytocin has therefore been considered a promising candidate for the treatment of social difficulties in ASD. However, evidence linking oxytocin treatment to social behavior and brain function in ASD is limited and heterogeneous effects might depend on variations in the oxytocin-receptor gene (OXTR). We examined 25 male ASD patients without intellectual disability in a double-blind, cross-over, placebo-controlled fMRI-protocol, in which a single dose of oxytocin or placebo was applied intranasally. Patients performed three experiments in the MRI examining empathy for other's physical pain, basic emotions, and social pain. All participants were genotyped for the rs53576 single-nucleotide polymorphism of the OXTR. Oxytocin increased bilateral amygdala responsiveness during the physical pain task for both painful and neutral stimuli. Other than that, there were no effects of oxytocin treatment. OXTR genotype did not significantly interact with oxytocin treatment. Our results contribute to the growing body of empirical literature suggesting heterogenous effects of oxytocin administration in ASD. To draw clinically relevant conclusions regarding the usefulness of oxytocin treatment, however, empirical studies need to consider methods of delivery, dose, and moderating individual factors more carefully in larger samples., (© 2021. The Author(s).)

It is not known how specific the neural mechanisms underpinning empathy for different domains are. In the present study, we set out to test whether shared neural representations between first-hand pain and empathy for pain are pain-specific or extend to empathy for unpleasant affective touch as well. Using functional magnetic resonance imaging and psychopharmacological experiments, we investigated if placebo analgesia reduces first-hand and empathic experiences of affective touch, and compared them with the effects on pain. Placebo analgesia also affected the first-hand and empathic experience of unpleasant touch, implicating domain-general effects. However, and in contrast to pain and pain empathy, administering an opioid antagonist did not block these effects. Moreover, placebo analgesia reduced neural activity related to both modalities in the bilateral insular cortex, while it specifically modulated activity in the anterior midcingulate cortex for pain and pain empathy. These findings provide causal evidence that one of the major neurochemical systems for pain regulation is involved in pain empathy, and crucially substantiates the role of shared representations in empathy., (© The Author(s) 2021. Published by Oxford University Press.)

Background: 3,4-Methylenedioxymethamphetamine (MDMA) is being actively researched as an adjunct to psychotherapy. It may be beneficial to trust, empathy and cooperative behaviour due to its acute prosocial effects., Aim: To test (a) the acute effects of MDMA on measures of empathy, trust and cooperative behaviour, and (b) subacute changes in mood three days after MDMA administration., Methods: Twenty-five participants ( n =7 female), participated in this double-blind, repeated-measures, placebo-controlled experiment. Participants attended two acute sessions, one week apart. Each acute session was followed by a subacute session three days later. Participants received placebo (100 mg ascorbic acid) during one acute session, and MDMA (100 mg MDMA-HCl) at the other, with order counterbalanced. Participants completed the following tasks assessing prosocial behaviour: a trust investment task, a trustworthy face rating task, an empathic stories task, a public project game, a dictator game and an ultimatum game. Participants reported subjective effects. Blood was taken pre-drug, 2 and 4 hours post-drug, and tested for plasma MDMA levels., Results: MDMA acutely increased self-reported 'closeness to others' and 'euphoria' and increased plasma concentrations of MDMA. MDMA did not significantly change task-based empathy, trust or cooperative behaviour. Using Bayesian analyses, we found evidence that MDMA and placebo did not differ in their effects on empathy and cooperative behaviour. MDMA did not significantly change subacute mood and this was supported by our Bayesian analyses., Conclusion: Despite augmentation in plasma MDMA levels and subjective drug effects, we found no increase in prosocial behaviour in a laboratory setting.

Objective: How Parkinson's disease (PD) affects an individual's empathic capacity remains poorly understood. By using the event-related potential (ERP) technique, we sought to: (1) study the temporal dynamics of empathic responses in patients with PD; (2) explore whether dopaminergic medication modulates empathic processing., Methods: Twenty-six patients with early-to-moderate PD (13 on- and 13 off-medication) and 14 healthy controls performed an empathy-for-pain paradigm test while we recorded their electroencephalography. The participants responded to neutral or painful pictures during an active empathic condition (pain judgment task) and a control condition that was manipulated by task demands (laterality judgment task)., Results: The ERP results demonstrated an early automatic frontal response and a late controlled parietal response to pain in healthy elderly controls. The observed early and late ERP responses were detected in the on-medication patients but not in the off-medication patients., Conclusions: PD is associated with deficits in both affective and cognitive empathic responses, dopaminergic medication may have the potential to alleviate these deficits., Significance: This study helps to understand empathic deficits in patients with PD. Within-subject studies are required to reliably assess the effect of dopaminergic medication on empathic processing., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Consolation behaviors toward the sick are common in humans. Anxiety in the relatives of the sick is also common. Anxiety can cause detrimental effects on multiple systems. However, our understanding on the neural mechanisms of these behaviors is limited because of the lack of small animal models. Methods: Five of 6- to 8-week-old CD-1 male mice were housed in a cage. Among them, 2 mice had right common artery exposure (surgery) and the rest were without surgery. Allo-grooming and performance in light and dark box and elevated plus maze tests of the mice were determined. Results: Mice without surgery had increased allo-grooming toward mice with surgery but decreased allo-grooming toward non-surgery intruders. This increased allo-grooming toward surgery mice was higher in familiar observers of surgery mice than that of mice that were not cage-mates of surgery mice before the surgery. Familiar observers developed anxious behavior after being with surgery mice. Surgery mice with familiar observers had less anxious behavior than surgery mice without interacting with familiar observers. Multiple brain regions including paraventricular thalamic nucleus (PVT) were activated in familiar observers. The activated cells in PVT contained orexin receptors. Injuring the neurons with ibotenic acid, antagonizing orexin signaling with an anti-orexin antibody or inhibiting neurons by chemogenetic approach in PVT abolished the consolation and anxious behaviors of familiar observers. Conclusions: Mice show consolation behavior toward the sick. This behavior attenuates the anxious behavior of surgery mice. The orexin signaling in the PVT neurons play a critical role in the consolation of familiar observers toward surgery mice and their anxious behavior. Considering that about 50 million patients have surgery annually in the United States, our study represents the initial attempt to understand neural mechanisms for consolation and anxiety of a large number of people., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Rationale: Recent research has shown that classical serotonergic psychedelic (CSP) drugs may be used to ameliorate certain health issues and disorders. Here we hypothesised that CSP experiences, through their ability to induce awe and ego-dissolution, may result in a reduction of maladaptive narcissistic personality traits, such as a strong sense of entitlement and lack of empathy., Objectives: Our objective was to investigate whether high levels of awe and ego dissolution during recent CSP experiences are associated with currently lower levels of maladaptive narcissism., Methods: In this pre-registered high-powered (N = 414) study, we used an online retrospective survey asking participants to describe their 'most awe-inspiring, impressive, significant, or emotionally intense experience', as well as several validated scales to test our hypothesis., Results: A statistically significant mediation model indicated that recent CSP-induced experiences were associated with currently increased feelings of connectedness and affective empathetic drive, which in turn were associated with decreased exploitative-entitled narcissism. This relationship held even when taking into account sensation-seeking personality features. We found no evidence for feelings of ego dissolution to have the same effect., Conclusions: Feelings of awe, but not ego dissolution, during recent CSP experiences were associated with increased feelings of connectedness and empathy, which in turn were associated with decreased levels of maladaptive narcissism personality features. This suggests that CSPs hold therapeutic potential for disorders involving connectedness and empathy, such as the treatment of pathological narcissism, and that the induction of connectedness through awe appears to be the driving force behind this potential.

Aim: Empathy is defined as the capability to comprehend and simulate the feelings of others. Though it has been considered as a human feature, recent studies have demonstrated empathy-like behaviors in other animals including rats. The objective of the current study was to evaluate the role of nitric oxide system in cognition and nociception changes following observation of cagemates in pain. Material and methods: Adult male Wistar rats were used ( n  = 8 for each group). One sibling received formalin injection into the hindpaw five times within a nine-day period and the other sibling observed the pain while being pretreated with saline, L-NAME or L-arginine (10 mg/kg, i.p.). Nociception, anxiety-like behavior and locomotion, balance, muscle strength, spatial and fear learning were evaluated. Results: Observing a family member (sibling) in pain increased anxiety-like behavior, led to a hyperalgesia in the observer and disruption of spatial memory. Nitric oxide system modulated these changes, so that in some paradigms the activation of NO and in some others inhibition of NO dampened the effect of observing pain in a cagemate on the evaluated features. Conclusions: Results in the current study demonstrated a modulating effect of NO on empathy induced changes in nociception, motor function and spatial memory. Further studies addressing the specific brain regions and other neurotransmitters involved are recommended.

Empathy for pain depends on the ability to feel, recognize, comprehend and share painful emotional conditions of others. In this study, we investigated the role of NO in a rat model of empathic pain. Pain was socially transferred from the sibling demonstrator (SD) who experienced five formalin injection to the naïve sibling observer (SO) through observation. SO rats received L-NAME (a nonspecific NO synthase inhibitor) or L-arginine (a precursor of NO) prior to observing the SD. Nociception, and concentrations of NO metabolites (NOx) in the serum, left and right hippocampus, prefrontal cortex, and cerebellum were evaluated. Nociceptive responses were significantly increased in the pain-observing groups. NOx levels measured 24 h after the last pain observation using the Griess method, were indicative of NOx concentration decreases and increases in the left hippocampus and cerebellum, respectively. There was an increase in tissue concentration of NOx in cerebellum and prefrontal cortex in both pain and observer groups 7 days after the fifth formalin injection. Our results suggest that NO is involved in development of empathic hyperalgesia, and observation of sibling's pain can change NO metabolites in different brain regions in observer rats.

Inter-group conflicts drive human discrimination, mass migration, and violence, but their psychobiological mechanisms remain largely unknown. Here, we investigated whether the neuropeptide oxytocin modulates behavior and spatio-temporal brain dynamics in naturalistic inter-group conflict. Eighty-six male members of natural rival social groups received either oxytocin or placebo intranasally. In a decision-making paradigm involving real monetary stakes, participants could sacrifice their own resources to modulate the monetary gains and losses of in- and out-group members. Oxytocin eliminated the reduction in out-group gains - particularly in individuals with low emotional empathy, whereas those given placebo exhibited this negative social behavior. Our spatio-temporal analysis of event-related potentials elicited by outcome valuation revealed that oxytocin replaced a neurophysiological process associated with the negative valuation of out-group gains via a process associated with positive valuation between 200-500ms after outcome presentation. Oxytocin thus seems to modulate inter-group behavior in humans via a specific alteration of valuation-related brain dynamics., Competing Interests: Declaration of Competing Interest All authors declare no competing interests., (Copyright © 2019. Published by Elsevier B.V.)

Borderline personality disorder (BPD) is characterized by severe interpersonal dysfunction with problems in social cognition, empathy and social approach. Although the neuropeptide oxytocin is known to regulate complex social cognition and behavior in healthy individuals and clinical populations, there is still a lack of evidence for a potential beneficial effect of oxytocin administration on social cognition and social approach in BPD. Fifty-one women with BPD and 51 matched healthy controls were randomized to a double-blind, placebo-controlled, between-subject experimental trial. We administered a single dose of 24 IU oxytocin or placebo intranasally prior to a standardized task measuring affective and cognitive empathy and approach motivation. All participants were free of hormonal contraception and tested in the mid-luteal phase of their menstrual cycle. In the placebo condition, patients with BPD showed reduced cognitive and affective empathy, and less approach behavior motivation than healthy controls. Intranasal oxytocin significantly increased affective empathy and approach motivation in both BPD patients and healthy controls compared to placebo. More importantly, oxytocin administration led to similar scores between BPD and healthy controls. These findings provide the first evidence for a beneficial effect of oxytocin on deficits in affective empathy and approach motivation of BPD. Our results indicate a beneficial effect of a single dose of oxytocin on affective empathy and approach motivation in women with BPD adapting their level of social functioning to healthy controls. Future clinical trials will need to investigate the long-term effects and effectiveness of oxytocin as an add-on treatment for social impairments in BPD.

Rationale: Hypothetical moral dilemmas, pitting characteristically utilitarian and non-utilitarian outcomes against each other, have played a central role in investigations of moral decision-making. Preferences for utilitarian over non-utilitarian responses have been explained by two contrasting hypotheses; one implicating increased deliberative reasoning, and the other implicating diminished harm aversion. In recent field experiments, these hypotheses have been investigated using alcohol intoxication to impair both social and cognitive functioning. These studies have found increased utilitarian responding, arguably as a result of alcohol impairing affective empathy., Objectives: The present research expands existing investigations by examining the acute effects of alcohol on affective empathy and subsequent moral judgments in traditional vignettes and moral actions in virtual reality, as well as physiological responses in moral dilemmas., Methods: Participants (N = 48) were administered either a placebo or alcohol in one of two dosages; low or moderate. Both pre- and post intervention, participants completed a moral action and moral judgment task alongside behavioural measures of affective empathy., Results: Higher dosages of alcohol consumption resulted in inappropriate empathic responses to facial displays of emotion, mirroring responses of individuals high in trait psychopathy, but empathy for pain was unaffected. Whilst affective empathy was influenced by alcohol consumption in a facial responding task, both moral judgments and moral actions were unaffected., Conclusions: These results suggest that facets, beyond or in addition to deficits in affective empathy, might influence the relationship between alcohol consumption and utilitarian endorsements.

Background: Previously, oxytocin, a neuropeptide implicated in human social cognition and behavior, was shown to improve people's ability to dynamically track another's emotional state ("empathic accuracy") specifically for less socially proficient individuals-i.e., healthy adults who score higher on the Autism Spectrum Quotient (AQ); conversely, oxytocin had no effect on empathic accuracy for more socially proficient individuals, who performed well following oxytocin and placebo. Here, we aimed to replicate this finding and investigate the effects of oxytocin on empathic accuracy in women. To date, women have been seriously underrepresented in human oxytocin research, and it is not known whether the effects observed in male-only samples apply to women., Methods: In this randomized, double-blind, placebo-controlled, crossover trial, we administered 24 IU intranasal oxytocin (and, on a separate occasion, a matching placebo) to 31 men and 40 women and then measured empathic accuracy. AQ was assessed at baseline (prior to drug administration)., Results: Replicating a 2010 study by Bartz et al., oxytocin selectively improved empathic accuracy for men who scored higher on the AQ, whereas oxytocin did not benefit their lower AQ counterparts. Conversely, we found no effect of oxytocin on empathic accuracy for women (regardless of their AQ score)., Conclusions: In addition to speaking to reliability, this research is important given interest in using oxytocin to augment social functioning in some psychiatric disorders marked by social cognitive impairments. More generally, this research adds to our understanding of the biological systems that support human sociality and provides further evidence for the role of oxytocin therein., (Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Rationale: Deficits in empathy constitute a distinctive feature of several psychopathologies, including conduct disorder (CD). The co-occurrence of callous-unemotional (CU) traits, excess rates of aggression and violation of societal norms confers specific risk for adult psychopathy. To date, the off-label use of methylphenidate (MPH) constitutes the drug treatment of choice., Objectives: Herein, we tested the therapeutic potential of MPH in a recently devised mouse model recapitulating the core phenotypic abnormalities of CD., Methods: Two subgroups of BALB/cJ male mice exhibiting opposite profiles of emotional contagion (i.e. socially transmitted adoption of another's emotional states) were investigated for reactive aggression, sociability, attention control, anxiety-related behaviours and locomotor activity, in response to MPH administration (0.0, 3.0 or 6.0 mg/kg)., Results: Our data indicate that mice selected for excess callousness exhibit phenotypic abnormalities isomorphic to the symptoms of CD: stability of the low emotional contagion trait, increased aggression and reduced sociability. In accordance with our predictions, MPH reduced aggression and increased sociability in callous mice; yet, it failed to restore the low responsiveness to the emotions of a conspecific in pain, isomorphic to CU traits., Conclusions: Although our data support the notion that MPH may contribute to the management of excess aggression in CD patients, additional studies shall identify specific treatments to target the callousness domain. The latter, unaffected by MPH in our experimental model, demands focused consideration whereby it constitutes a specifier associated with a worse prognosis.

Acting without the expectation of compensation is called prosocial behaviour. Since prosocial behaviour requires high cognitive and social abilities, it has been thought to be only shown by primates. Although prosocial behaviour has been recently reported in rats, there are still questions regarding this finding. We demonstrated rescue-like behaviour in mice in a previous report. In this study, we investigated the motives underlying rescue-like behaviour for constrained cage-mates among mice. We prepared either a tube containing a ball of yarn or an opaque tube and assessed whether mice displayed the same rescue-like behaviour shown in the case of tube-restrained cage-mates. Mice did not open the lid of the tube containing the ball of yarn but opened the opaque tube lid. Mice showed a high interest in the tube in which the cage-mate had been restrained and prioritized staying in this tube rather than rescuing additional cage-mates. Oxytocin, which increases empathy, had no effect on the lid-opening behaviour. Thus, the rescue-like behaviour of mice is not based on empathy but is related to social interest in the cage-mate and the tube itself. These results suggest that rodent lid-opening behaviour may not conclusively prove the presence of prosocial behaviour.

Previous research has revealed a positive effect of oxytocin administration on several social behaviors especially in individuals with social-affective deficits. However, it is still unknown whether intranasal oxytocin administration (OT-IN) can be beneficial to residential youth who exhibit severe social-affective impairments. We conducted a randomized, double-blind, placebo-controlled, within-subjects, sequential study to examine the effect of OT-IN on empathy and emotion recognition in 100 male adolescents living in residential youth care facilities. We also explored the moderating role of callous-unemotional traits, trauma, and dissociation in the oxytocin effect. Participants self-administered one dose of 24 IU of oxytocin or placebo and performed experimental tasks on empathy and emotion recognition before and after the administration. The same procedure was performed one week later with the other substance. We found that empathy was increased after oxytocin administration compared to placebo and this effect was specific to individuals with high callous-unemotional traits. There was no effect of OT-IN on the overall emotion recognition, but there was a positive effect on accuracy of fear recognition. Trauma and dissociation did not moderate the oxytocin effect on empathy or emotion recognition. Our findings provided evidence of a beneficial effect of OT-IN on empathy and fear recognition in residential youth. We propose that a combination of OT-IN and psychological interventions merits further exploration, as it might be a novel promising direction for more tailored approaches and better treatment outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: While the neuropeptide oxytocin can facilitate empathy and altruistic behavior, it may also promote self-serving tendencies in some contexts, and it remains unclear if it would increase altruistic or self-interest behaviors when they compete within a social situation., Methods: The current between-subject, double-blind, placebo-controlled fMRI study investigated the effect of intranasal oxytocin on empathy for social exclusion using a modified online ball-tossing game that incorporated monetary rewards and the potential to display both altruistic and self-interest behaviors., Results: Results showed that when subjects in both oxytocin and placebo groups were observing a player being excluded (victim) by other players in the game, there was activation in the mentalizing network. When subjects then played both with the victim and the players who had excluded them, they threw more balls to the victim player, indicative of an altruistic response. However, subjects in the oxytocin group threw more balls to the excluder players indicative of greater self-interest, since the latter would be perceived as more likely to reciprocate to maximize financial gain. This behavioral effect of oxytocin was associated with greater medial orbitofrontal cortex activation when playing with the excluders and negatively correlated with trait-altruism scores., Conclusions: Overall, our findings suggest that in the context of competing motivations for exhibiting altruistic or self-interest behavior, oxytocin enhanced self-interest and this was associated with greater activation in frontal reward areas., (© The Author(s) 2019. Published by Oxford University Press on behalf of CINP.)

The steroid hormone cortisol is released in response to stress and exerts its effects in the brain via two different receptors: the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). This review - dedicated to Dirk Hellhammer - focusses on the role of MR on cognitive and emotional function in healthy individuals and in stress-associated disorders such as major depressive disorder (MDD) or borderline personality disorder (BPD). Animal data and studies from healthy individuals converge such that MR play an important role in the appraisal of new situations and the following response selection. Decision-making and empathy are important determinants of this response selection and both are affected by MR function. Furthermore, MR are crucially involved in visuospatial navigation and memory in young and elderly healthy individuals whereas the exact physiological role of MR in verbal learning and verbal memory needs to be further characterized. In contrast to studies in healthy participants, age played a moderating role on the effects of MR stimulation on cognition in depressed patients. In young depressed patients, MR stimulation exerted beneficial effects on verbal memory and executive function, whereas in elderly depressed patients MR stimulation led to impaired verbal learning and visuospatial memory. Similar to healthy controls, BPD patients showed enhanced emotional empathy but not cognitive empathy after MR stimulation. Accordingly, this make MR an interesting target for potential pharmacological augmentation of psychotherapy in BPD. Given the important role MR play in cognitive and emotional function in health and disease, further studies should examine whether MR modulation can alleviate cognitive and emotional problems in patients with stress-associated disorders., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Major depressive disorder (MDD) has been hypothesized to lead to impairments in empathy. Previous cross-sectional studies did not disentangle effects of MDD itself and antidepressant treatment. In this first longitudinal neuroimaging study on empathy in depression, 29 patients with MDD participated in two functional magnetic resonance imaging (fMRI) sessions before and after 3 months of antidepressant therapy. We compared their responses to an empathy for pain task to a group of healthy controls (N = 35). All participants provided self-report ratings targeting cognitive (perspective taking) and affective (unpleasant affect) aspects of empathy. To control for general effects on processing of negative affective states, participants additionally underwent an electrical pain task. Before treatment, we found no differences in empathic responses between controls and patients with MDD. After treatment, patients showed significant decreases in both affective empathy and activity of three a priori selected brain regions associated with empathy for pain. Decreases in affective empathy were moreover correlated with symptom improvement. Moreover, functional connectivity during the empathy task between areas associated with affective (anterior insula) and cognitive (precuneus) empathy decreased between sessions in the MDD group. Neither cognitive empathy nor responses to painful electrical shocks were changed after treatment. These findings contradict previous cross-sectional reports of empathy deficits in acute MDD. Rather, they suggest that antidepressant treatment reduces the aversive responses triggered by exposure to the suffering of others. Importantly, this cannot be explained by a general blunting of negative affect, as treatment did not change self-experienced pain.

Creative thinking and empathy are crucial for everyday interactions and subjective well-being. This is emphasized by studies showing a reduction in these skills in populations where social interaction and subjective well-being are significantly compromised (e.g., depression). Anecdotal reports and recent studies suggest that a single administration of psilocybin can enhance such processes and could therefore be a potential treatment. However, it has yet to be assessed whether effects outlast acute intoxication. The present study aimed to assess the sub-acute effects of psilocybin on creative thinking, empathy, and well-being. Participants attending a psilocybin retreat completed tests of creative (convergent and divergent) thinking and empathy, and the satisfaction with life scale on three occasions: before ingesting psilocybin ( N = 55), the morning after ( N = 50), and seven days after ( N = 22). Results indicated that psilocybin enhanced divergent thinking and emotional empathy the morning after use. Enhancements in convergent thinking, valence-specific emotional empathy, and well-being persisted seven days after use. Sub-acute changes in empathy correlated with changes in well-being. The study demonstrates that a single administration of psilocybin in a social setting may be associated with sub-acute enhancement of creative thinking, empathy, and subjective well-being. Future research should test whether these effects contribute to the therapeutic effects in clinical populations.

Background: 3,4-Methylenedioxymethamphetamine (MDMA) is widely known for its positive acute effects on social behaviour, such as increasing empathy, whilst also attenuating the negative impact of social exclusion. However there is a scarcity of research that investigates the long-term impact of recreational MDMA use on these fundamental social processes., Method: Sixty-seven individuals were split into three groups based on their drug-use history: poly-drug MDMA users ( n = 25), poly-drug users who do not use MDMA ( n = 19), alcohol-only users ( n = 23), and were tested in an independent groups design. Participants completed both a self-report measure of emotional and cognitive empathy, along with the Multifaceted Empathy Task - a computerised assessment of empathy - and the Cyberball Game - a social exclusion paradigm., Results: MDMA users had significantly greater subjective emotional empathy, and greater cognitive empathy on the computer task compared with the poly-drug users who do not use MDMA. There were no significant differences in subjective responses to social exclusion between the groups. Indices of MDMA use did not correlate with empathy., Conclusions: Long-term MDMA users in this sample exhibited normal psychosocial functioning in regard to empathy and social pain and had higher subjective emotional empathy. This conflicts with previous suggestions that moderate, long-term MDMA use may cause heightened social distress, and is further evidence of the safety of the drug, which is relevant to considerations of its therapeutic use.

The effects of intranasal oxytocin, a neuropeptide involved in prosocial behavior and modulation of neural networks underlying social cognition and emotion regulation, have been studied in schizophrenia. We tested the hypothesis that twice-daily intranasal oxytocin administered for 12-weeks would improve tertiary and exploratory outcomes of self-reported social symptoms, empathy and introspective accuracy from the Jarskog et al. (2017) randomized controlled trial. Sixty-eight stable outpatients with schizophrenia or schizoaffective disorder were randomized to receive oxytocin (24 IU twice daily) or placebo. Introspective accuracy was assessed with the Specific Level of Functioning Scale and the Interpersonal Perception Task. Empathy was assessed with the Interpersonal Reactivity Index (IRI), and social symptoms were assessed with the Liebowitz Social Anxiety Scale and the Green et al. Paranoid Thoughts Scales. Outcomes were assessed at baseline, six, and twelve weeks. Results demonstrated limited effect of oxytocin with some improvement on the IRI Perspective-Taking Subscale. No additional between-group differences emerged on self-reported symptoms, empathy, or introspective accuracy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Rationale: Non-medical prescription opioid use (NMPOU) has become a major public health issue in the USA and is also increasing in Europe. However, little is known about neuropsychological associations of NMPOU-specifically regarding social cognition, which is essential for social functioning and treatability of opioid dependence. Previous studies with heroin users and opioid-substituted patients reported deficits in various cognitive functions, but these results are likely confounded by comorbid physical and psychiatric diseases, overdose-associated hypoxia, and adulteration of street heroin. Therefore, the purpose of the present study was to investigate social and non-social cognition in a relatively pure NMPOU sample taking opioid analgesics or antitussives., Methods: We assessed 23 individuals with NMPOU objectively confirmed by hair analyses and 29 opioid-naïve, healthy controls, employing a comprehensive neuropsychological test battery., Results: Significant impairments were found between NMPOU individuals and controls regarding the cognitive domains of attention (p < .01, Hedge's g = .85), declarative memory (p < .05, g = .66), and global cognitive empathy (p < .01, g = 0.99)-the latter included problems with emotion recognition from faces, voices, and complex scenes. Opioid hair concentrations transformed to morphine equivalents were negatively correlated with global cognitive empathy (r = - 0.52, p < .01), suggesting dose-dependent deficits., Conclusion: In contrast to stimulant users primarily displaying deficits in emotional empathy, opioid users showed relatively selective impairments in measures of cognitive empathy, with dose-dependent effects suggesting potential opioid-induced deficits and involvement of the opioid-system in processes of cognitive empathy. These results have important implications for future interventions of opioid dependence targeting social functioning and consequently enhancing therapy outcome and preventing relapse.

Deficits in empathy, the ability to share an emotion of another individual, constitute a hallmark of several psychopathological conditions, including conduct disorder. The co-occurrence of excess rates of aggression, general violation of societal norms and callous-unemotional traits confers specific risk for adult psychopathy. In the present study, we relied on a recently devised experimental model of conduct disorder in mice to test the potential efficacy of intranasal oxytocin administration. Two subgroups of BALB/cJ male mice exhibiting opposite profiles in emotional contagion (i.e. socially transmitted adoption of another's emotional states) underwent a series of tests mapping onto reactive aggression, information processing, perseverative behaviour, punishment-related emotional memory, physiological arousal and hormonal stress reactivity, with or without intranasal oxytocin administration (5.0 or 20.0 μg/kg). Collectively, our data indicate that a trait of markedly reduced emotional contagion is associated with a behavioural syndrome of sensorimotor gating deficits, impaired emotional memory, increased aggression and stereotyped behaviours, dysregulations in the circadian rhythms of activity and body temperature and dampened physiological reactivity to external stressors. Moreover, in the absence of changes in oxytocin receptor density in the neural network involved in empathy-like behaviour, we showed that oxytocin administration normalised emotional contagion, aggression and behavioural stereotypies, thereby ameliorating the phenotype of mice characterised by deficient empathy-like behaviour. Besides, oxytocin led to a lower, more prolonged neuroendocrine response of the HPA-axis to stress in all mice. Ultimately, current data support the notion that oxytocin may constitute a valid therapeutic approach in disturbances characterised by abnormal aggression and excess callousness., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Autism spectrum disorders (ASDs) are neurodevelopmental conditions with impairments in social communication and interaction. Empathy is the ability to understand and share another person's inner life, and it is an essential process in social cognition, which is deficient in ASD. The mismatch field (MMF) has been used as a neurophysiological marker for the automatic detection of changes in auditory stimuli. In the present study, we focused on long-term changes in MMF evoked by an empathic voice and changes in the empathy quotient (EQ) in ASD during an 8-week clinical trial using oxytocin (OT). Ten males with ASD without intellectual disability participated in this pilot study. The results demonstrated a significant positive correlation between the change in the MMF amplitude in the auditory cortex (i.e., right banks of the superior sulcus) and the change in the EQ score during the 8-week clinical trial, whereas no significant change was observed in the MMF amplitude or EQ score after the administration period of OT. Although we cannot conclude that the observed relationships were caused by OT's effect or by natural changes, our results suggest that MMF evoked by social voice can be a state-dependent marker of empathic abilities in male adults with ASD., (Copyright © 2018. Published by Elsevier B.V.)

Objectives: 4-Fluoroamphetamine (4-FA) is a novel psychoactive substance with a pharmacological profile and reported subjective effects (e.g., empathy) intermediate between 3,4-methylenedioxymethamphetamine (MDMA) and amphetamine. Studies have shown that MDMA and amphetamine increase emotional empathy without affecting cognitive empathy; MDMA simultaneously leads to elevated levels of oxytocin, unrelated to its behavioral effects. The aim of the present study was to assess the reported enhancement of empathy by 4-FA, to assess its effects on oxytocin, and to test potential associations between both., Methods: Twelve healthy poly-drug users were included in a double-blind placebo-controlled two-way crossover study. Treatments were 4-FA (100 mg) and placebo; empathy was assessed by means of the multifaceted empathy test, and blood samples were taken before and after treatment administration to determine oxytocin concentrations., Results: 4-FA reduced cognitive empathy, whereas emotional empathy was left unaffected. One hour after treatment, plasma oxytocin levels were significantly increased compared with placebo. Behavioral and hormonal effects were unrelated., Conclusion: Although 4-FA shares its pharmacological mechanism with MDMA and amphetamine, current findings seem to indicate that it affects empathy differently. The 4-FA-induced increase in oxytocin levels was independent of behavioral effects, which confirms previous findings that drug-induced effects on peripheral oxytocin levels are not associated with empathy., (© 2018 John Wiley & Sons, Ltd.)

Background: Using more than one psychotropic substance is accompanied by increased risks for psychiatric and physical disorders. Accordingly, deficits in basal cognitive functions have been consistently associated with polysubstance use (PSU), whereas little is known about potential impairments in more complex socio-cognitive skills, which are relevant for daily-life functioning. Therefore, we investigated the effects of toxicological validated stimulant PSU on social cognition under consideration of potential cumulative effects., Methods: We compared socio-cognitive performances of 47 individuals with stimulant PSU with 59 matched stimulant-naïve controls using the Multifaceted Empathy Test (MET) and the Movie for the Assessment of Social Cognition (MASC). Additionally, social network size was assessed by the Social Network Questionnaire (SNQ). Hair and urine testing was employed to categorize three PSU subgroups (3, 4, and ≥5 substances used) and to ensure drug abstinence in controls., Results: Individuals with stimulant PSU showed lower emotional empathy (MET) and a smaller social network (SNQ) compared to controls (both with linear trends for increasing number of used substances: p < .05). In contrast, cognitive empathy (MET and MASC) was largely unaffected by PSU. Additional linear regression analyses within PSU individuals revealed number of used substances as the best predictor for inferior performance in emotional empathy (p < .01), while severity of the use of single substances or substance-classes did not show a significant impact., Conclusion: These findings demonstrate cumulative adverse effects of stimulant PSU on an important facet of socio-cognitive functioning. Therefore, emotional empathy deficits should be targeted in future interventions and rehabilitations for individuals with PSU., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Methylenedioxymethamphetamine (MDMA) increases oxytocin, empathy, and prosociality. Oxytocin plays a critical role in emotion processing and social behavior and has been shown to mediate the prosocial effects of MDMA in animals. Genetic variants, such as single-nucleotide polymorphisms (SNPs), of the oxytocin receptor (OXTR) may influence the emotional and social effects of MDMA in humans. The effects of common genetic variants of the OXTR (rs53576, rs1042778, and rs2254298 SNPs) on the emotional, empathogenic, and prosocial effects of MDMA were characterized in up to 132 healthy subjects in a pooled analysis of eight double-blind, placebo-controlled studies. In a subset of 53 subjects, MDMA produced significantly greater feelings of trust in rs1042778 TT genotypes compared with G allele carriers. The rs53576 and rs225498 SNPs did not moderate the subjective effects of MDMA in up to 132 subjects. None of the SNPs moderated MDMA-induced impairments in negative facial emotion recognition or enhancements in emotional empathy in the Multifaceted Empathy Test in 69 subjects. MDMA significantly increased plasma oxytocin concentrations. MDMA and oxytocin concentrations did not differ between OXTR gene variants. The present results provide preliminary evidence that OXTR gene variations may modulate aspects of the prosocial subjective effects of MDMA in humans. However, interpretation should be cautious due to the small sample size. Additionally, OXTR SNPs did not moderate the subjective overall effect of MDMA (any drug effect) or feelings of "closeness to others"., Trial Registration: ClinicalTrials.gov: http://www.clinicaltrials.gov, No: NCT00886886, NCT00990067, NCT01136278, NCT01270672, NCT01386177, NCT01465685, NCT01771874, and NCT01951508., Competing Interests: The authors have declared that no competing interests exist.

Rationale: Drinking alcohol is associated with various interpersonal effects, including effects on cognitive empathy. Empathic accuracy (EA) is a form of cognitive empathy concerned with perceivers' accuracy in inferring a target's thoughts and feelings. The effects of alcohol on EA have not previously been studied., Objectives: We examined the effect of a moderate alcohol dose on EA in social drinkers., Methods: Fifty-four men with varying levels of hazardous drinking according to the Alcohol Use Disorders Identification Test (AUDIT) participated in a randomized, double-blind, between-group study. The alcohol group received 0.56 g/kg alcohol in a vodka and tonic-mixed drink. The placebo group received tonic, with 4 ml of vodka sprayed on top. All participants performed an EA task that involved watching 16 videos of people narrating positive and negative emotional autobiographical events and continuously rating how targets felt while narrating., Results: There were no significant main effects of beverage condition on the EA task. There was an effect of the condition by AUDIT interaction for EA on the positive videos. Post-hoc simple contrasts revealed that in participants with lower AUDIT scores, the alcohol condition had lower EA for positive videos than the placebo condition. No significant main effect for condition occurred in the participants with higher AUDIT scores., Conclusions: The effect of condition in participants with lower AUDIT scores indicates alcohol selectively reduced EA in individuals low on hazardous drinking. This suggests either alcohol-induced impairments of EA for positive events or a positivity bias in men at low risk for alcohol dependency.

Background: The empathogen 3,4-methylenedioxymethamphetamine (MDMA) is the prototypical prosocial club drug inducing emotional openness to others. It has recently been shown that acutely applied 3,4-MDMA in fact enhances emotional empathy and prosocial behavior, while it simultaneously decreases cognitive empathy. However, the long-term effects of 3,4-MDMA use on socio-cognitive functions and social interactions have not been investigated yet. Therefore, we examined emotional and cognitive empathy, social decision-making, and oxytocin plasma levels in chronic 3,4-MDMA users., Methods: We tested 38 regular but recently abstinent 3,4-MDMA users and 56 3,4-MDMA-naïve controls with the Movie for the Assessment of Social Cognition, the Multifaceted Empathy Test, and the Distribution Game and the Dictator Game. Drug use was objectively quantified by 6-month hair analyses. Furthermore, oxytocin plasma levels were determined in smaller subgroups (24 3,4-MDMA users, 9 controls)., Results: 3,4-MDMA users showed superior cognitive empathy compared with controls in the Multifaceted Empathy Test (Cohen's d=.39) and in the Movie for the Assessment of Social Cognition (d=.50), but they did not differ from controls in emotional empathy. Moreover, 3,4-MDMA users acted less self-serving in the Distribution Game. However, within 3,4-MDMA users, multiple regression analyses showed that higher 3,4-MDMA concentrations in hair were associated with lower cognitive empathy (βMDMA=-.34, t=-2.12, P<.05). Oxytocin plasma concentrations did not significantly differ between both groups., Conclusions: We conclude that people with high cognitive empathy abilities and pronounced social motivations might be more prone to 3,4-MDMA consumption. In contrast, long-term 3,4-MDMA use might nevertheless have a detrimental effect on cognitive empathy capacity.

Deficits in social cognition are pervasive and characteristic of neurodevelopmental disorders (NDDs). Clinical trials of intranasal oxytocin (IN-OT) to improve social cognition have yielded inconclusive results. The current study is a meta-analysis of randomized controlled trials (RCTs) considering the effect of IN-OT on social cognitive domains across a range of NDDs. Medline, PsychINFO and Scopus were searched for RCTs published through to July 25, 2017. Seventeen studies met inclusion criteria, comprising 466 participants with a NDD. Meta-analysis using a random-effects model, revealed that IN-OT had no significant effect on emotion recognition (Hedges' g=0.08), a moderate but non-significant effect on empathy (Hedges' g=0.49), and a small, significant effect on theory of mind (ToM) (Hedges' g=0.21). Meta-regression indicated that the effect of IN-OT on social cognition was not moderated by the diagnosis or age of participants, or the dose or frequency of IN-OT administration. The results highlight a need for more well-designed RCTs, as it remains difficult to draw conclusions about the potential for IN-OT to improve social cognition in NDDs. The promise of IN-OT should be considered tentative., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The neuropeptide oxytocin (OT) has emerged as a potent modulator of diverse aspects of interpersonal relationships. OT appears to work in close interaction with several other neurotransmitter networks, including the dopaminergic reward circuit, and to be dependent on sex-specific hormonal influences. In this chapter, we focus on four main domains of OT and interpersonal relationships, including (1) the protective effect of OT on an individual's ability to withstand stress (i.e., stress buffering), (2) the effect of OT on emotion recognition and empathy, (3) OT's ability to enhance social synchrony and cooperation among individuals, and (4) the effect of OT on an individual's perception of social touch. We then illustrate the connection between OT and loneliness while grieving the loss of a loved one. We finish by discussing the clinical potential of OT, focusing on its potential role as an adjunct to psychotherapy, its enhancement through sex-specific hormonal influences, and the difficulties that present themselves when considering OT as a therapy. Overall, we argue that OT continues to hold strong therapeutic promise, but that it is strongly dependent on internal and external influences, for instance the patient's personal past experiences and interaction with the therapist, in order to provide the best possible therapy.

Oxytocin (OXT) has previously been implicated in a range of prosocial behaviors such as trust and emotion recognition. Nevertheless, recent studies have questioned the evidence for this link. In addition, there has been relatively little conclusive research on the effect of OXT on empathic ability and such studies as there are have not examined the mechanisms through which OXT might affect empathy, or whether OXT selectively facilitates empathy for specific emotions. In the current study, we used eye-tracking to assess attention to socially relevant information while participants viewed dynamic, empathy-inducing video clips, in which protagonists expressed sadness, happiness, pain or fear. In a double-blind, within-subjects, randomized control trial, 40 healthy male participants received 24 IU intranasal OXT or placebo in two identical experimental sessions, separated by a 2-week interval. OXT led to an increase in time spent fixating upon the eye-region of the protagonist's face across emotions. OXT also selectively enhanced self-reported affective empathy for fear, but did not affect cognitive or affective empathy for other emotions. Nevertheless, there was no positive relationship between eye-gaze patterns and affective empathy, suggesting that although OXT influences eye-gaze and may enhance affective empathy for fear, these two systems are independent. Future studies need to further examine the effect of OXT on eye-gaze to fully ascertain whether this can explain the improvements in emotional behavior., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Behaviour may be influenced by pituitary hormones or treatments. Dopamine agonist (DA) indicated in prolactinomas treatment can cause side effects, and especially impulse control disorders. In the context of prolactinomas treatment, impulse control disorders (ICD) have been reported like gambling, compulsive shopping, but mostly hypersexuality. These ICD can occur with low AD doses, and seem to be independent of type of molecule and psychiatric medical history. The main pathophysiologic hypothesis is a dysregulation of dopaminergic pathway involved in reward system. Given the possible devastating social impact of these ICD, they have to be screened in patients treated with DA. Our social behaviour can also be impacted by oxytocin. This hormone secreted on physiologic state at posterior pituitary, but also by others areas of brain and brainstem, has an impact on attachment in pair partners and in parent-child relationship, but also in empathy behaviour. Oxytocin affects as well eating behaviour with an anorexigenic impact. Studies on small populations assessed the relevance of an oxytocin treatment in several endocrine and nutritional pathologies like post-surgery craniopharyngioma, panhypopituitarism and obesity. Despite promising results, several pitfalls prevent yet the oxytocin use in clinical practice., (© 2017 Elsevier Masson SAS. Tous droits réservés.)

The oxytocinergic system is crucial for sociality and well-being and is associated with empathy. It is suggested that the oxytocinergic system exerts context- and person-dependent effects. We examined how sexual sadistic contexts influenced the effects of the oxytocinergic system on empathic-related behaviors and brain activity in healthy adults. Combining genetic neuroimaging, pharmacological techniques and a psychological paradigm of empathy, we recorded EEG neural responses in female OXTR rs53756 G/G and A/A carriers and measured subjective empathic ratings after intranasal administration of oxytocin/placebo in healthy male adults during the perception of painful facial expressions in sadistic/general social contexts. The results revealed that sadistic contexts modulate oxytocinergic effects on empathy at both behavioral and neural levels. The oxytocinergic system preferentially modulated empathic responses to sadistic contexts. These effects are moderated by individual's trait empathy. Our combined genetic-pharmacological-imaging results provide a neurochemical mechanism for sadistic context-dependent effects of the oxytocinergic system on empathy.

Background: Impaired empathic abilities lead to severe negative social consequences and influence the development and treatment of several psychiatric disorders. Furthermore, empathy has been shown to play a crucial role in moral and prosocial behavior. Although the serotonin system has been implicated in modulating empathy and moral behavior, the relative contribution of the various serotonin receptor subtypes is still unknown., Methods: We investigated the acute effect of psilocybin (0.215 mg/kg p.o.) in healthy human subjects on different facets of empathy and hypothetical moral decision-making using the multifaceted empathy test (n=32) and the moral dilemma task (n=24)., Results: Psilocybin significantly increased emotional, but not cognitive empathy compared with placebo, and the increase in implicit emotional empathy was significantly associated with psilocybin-induced changed meaning of percepts. In contrast, moral decision-making remained unaffected by psilocybin., Conclusions: These findings provide first evidence that psilocybin has distinct effects on social cognition by enhancing emotional empathy but not moral behavior. Furthermore, together with previous findings, psilocybin appears to promote emotional empathy presumably via activation of serotonin 2A/1A receptors, suggesting that targeting serotonin 2A/1A receptors has implications for potential treatment of dysfunctional social cognition., (© The Author 2017. Published by Oxford University Press on behalf of CINP.)

Neuroimaging studies have shown that seeing others in pain activates brain regions that are involved in first-hand pain, suggesting that shared neuromolecular pathways support processing of first-hand and vicarious pain. We tested whether the dopamine and opioid neurotransmitter systems involved in nociceptive processing also contribute to vicarious pain experience. We used in vivo positron emission tomography to quantify type 2 dopamine and μ-opioid receptor (D2R and MOR, respectively) availabilities in brains of 35 subjects. During functional magnetic resonance imaging, the subjects watched short movie clips depicting persons in painful and painless situations. Painful scenes activated pain-responsive brain regions including anterior insulae, thalamus and secondary somatosensory cortices, as well as posterior superior temporal sulci. MOR availability correlated negatively with the haemodynamic responses during painful scenes in anterior and posterior insulae, thalamus, secondary and primary somatosensory cortices, primary motor cortex, and superior temporal sulci. MOR availability correlated positively with orbitofrontal haemodynamic responses during painful scenes. D2R availability was not correlated with the haemodynamic responses in any brain region. These results suggest that the opioid system contributes to neural processing of vicarious pain, and that interindividual differences in opioidergic system could explain why some individuals react more strongly than others to seeing pain., (© The Author 2017. Published by Oxford University Press.)

This study investigates paternal brain function with the hope of better understanding the neural basis for variation in caregiving involvement among men. The neuropeptides oxytocin (OT) and vasopressin (AVP) are implicated in paternal caregiving in humans and other species. In a double-blind, placebo-controlled, within-subject pharmaco-functional MRI experiment, we randomized 30 fathers of 1-2year old children to receive either 24IU intranasal OT before one scan and placebo before the other scan (n=15) or 20IU intranasal AVP before one scan and placebo before the other scan (n=15). Brain function was measured with fMRI as the fathers viewed pictures of their children, unknown children and unknown adults, and as they listened to unknown infant cry stimuli. Intranasal OT, but not AVP, significantly increased the BOLD fMRI response to viewing pictures of own children within the caudate nucleus, a target of midbrain dopamine projections, as well as the dorsal anterior cingulate (dACC) and visual cortex, suggesting that intranasal oxytocin augments activation in brain regions involved in reward, empathy and attention in human fathers. OT effects also varied as a function of order of administration such that when OT was given before placebo, it increased activation within several reward-related structures (substantia nigra, ventral tegmental area, putamen) more than when it was given after placebo. Neither OT nor AVP had significant main effects on the neural response to cries. Our findings suggest that the hormonal changes associated with the transition to fatherhood are likely to facilitate increased approach motivation and empathy for children, and call for future research that evaluates the potential of OT to normalize deficits in paternal motivation, as might be found among men suffering from post-partum depression., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to compare children and adolescents with attention-deficit/hyperactivity disorder (ADHD) to healthy children and adolescents in terms of state and trait empathy and emotion expression recognition skills. The goal was also to determine whether there are changes in emotion recognition and empathy measures in children with ADHD after methylphenidate (MPH) treatment., Methods: The research sample consisted of outpatient drug-naive children and adolescents between the age of 8 and 14 years (n = 65) with ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. criteria, and healthy children and adolescents of the same age (n = 61). Scores of the oppositional problems (OPs) and conduct problems (CPs) were obtained to evaluate their impact on children's empathy skills with the Child Behavior Checklist. Self-reported (Bryant Index of Empathy, BEI) and parent-reported (Griffith Empathy Measurement-Parent Rating, GEM-PR) scales were used to evaluate trait empathy. The Empathy Response Task (ERT) was used to evaluate state empathy, and the Diagnostic Analysis of Nonverbal Accuracy-2 (DANVA-2) was used to evaluate facial expression recognition skills. The scales and tests were repeated after 12 weeks of MPH treatment in the ADHD group., Results: There were no significant statistical differences in trait empathy skills evaluated by parent-reported and self-reported measures, ERT, and DANVA-2 scores. In self-reported measures, the girls had higher scores than boys. From the results of the regression analysis, it was concluded that OPs were not associated with the measures. However, CPs were associated with the scores of the BEI, GEM-PR, and the match scores of the ERT. The average dosage of MPH in the group with ADHD was 0.83 ± 0.21 mg/(kg·d). While there was no change in the BEI and GEM-PR scores after 12 weeks of treatment, there was a significant increase in the ERT interpretation subscore and a significant decrease in the recognition error of anger and sadness expressions in the DANVA-2., Conclusions: The findings of our study suggest that children with ADHD have similar levels of trait and state empathy skills and facial expressions as healthy controls and CPs negatively affect their empathy skills. MPH treatment does not change trait empathy skills, yet there are some improvements in state empathy skills.

Objective: To assess the Empathizing Quotient (EQ) of patients diagnosed with attention-deficit/hyperactivity disorder (ADHD) only or comorbid with oppositional defiant disorder (ODD) and compare the two groups' responses to methylphenidate (MPH) treatment., Methods: Fifty-two children (8-18 years) diagnosed with ADHD, 26 of whom were also diagnosed with comorbid ODD (ADHD/ODD), were treated with MPH for 12 weeks. The level of EQ was assessed with the Children's version of the Empathizing Quotient (EQ-C) and the severity of ADHD symptoms with the ADHD Rating Scale (ADHD-RS). Assessments were done at baseline and at end point., Results: A significant increase in EQ scores was obtained in both groups following MPH treatment (p = 0.003 for ADHD/ODD; p = 0.002 for ADHD). Significant correlation was found in the ADHD group between the changes in ADHD-RS and those in EQ, following MPH treatment (p = 0.015), but not in the ADHD/ODD group (p = 0.48)., Conclusions: A correlation exists between MPH-related improvement in ADHD symptoms and between more empathy in children with ADHD not comorbid with ODD.

Previous placebo-controlled experimental studies have shown that a single dose of MDMA can increase emotional empathy in the multifaceted empathy test (MET) without affecting cognitive empathy. Although sufficiently powered to detect main effects of MDMA, these studies were generally underpowered to also validly assess contributions of additional parameters, such as sex, drug use history, trait empathy and MDMA or oxytocin plasma concentrations. The present study examined the robustness of the MDMA effect on empathy and investigated the moderating role of these additional parameters. Participants ( n = 118) from six placebo-controlled within-subject studies and two laboratories were included in the present pooled analysis. Empathy (MET), MDMA and oxytocin plasma concentrations were assessed after oral administration of MDMA (single dose, 75 or 125 mg). Trait empathy was assessed using the interpersonal reactivity index. We confirmed that MDMA increased emotional empathy at both doses without affecting cognitive empathy. This MDMA-related increase in empathy was most pronounced during presentation of positive emotions as compared with negative emotions. MDMA-induced empathy enhancement was positively related to MDMA blood concentrations measured before the test, but independent of sex, drug use history and trait empathy. Oxytocin concentrations increased after MDMA administration but were not associated with behavioral effects. The MDMA effects on emotional empathy were stable across laboratories and doses. Sex did not play a moderating role in this effect, and oxytocin levels, trait empathy and drug use history were also unrelated. Acute drug exposure was of significant relevance in the MDMA-induced emotional empathy elevation.