Advances in human oxytocin measurement: challenges and proposed solutions.

Oxytocin, a neuropeptide known for its role in reproduction and socioemotional processes, may hold promise as a therapeutic agent in treating social impairments in patient populations. However, research has yet to uncover precisely how to manipulate this system for clinical benefit. Moreover, inconsistent use of standardized and validated oxytocin measurement methodologies-including the design and study of hormone secretion and biochemical assays-present unresolved challenges. Human studies measuring peripheral (i.e., in plasma, saliva, or urine) or central (i.e., in cerebrospinal fluid) oxytocin concentrations have involved very diverse methods, including the use of different assay techniques, further compounding this problem. In the present review, we describe the scientific value in measuring human endogenous oxytocin concentrations, common issues in biochemical analysis and study design that researchers face when doing so, and our recommendations for improving studies using valid and reliable methodologies.

Null results of oxytocin and vasopressin administration on mentalizing in a large fMRI sample: evidence from a randomized controlled trial.

BACKGROUND: Although potential links between oxytocin (OT), vasopressin (AVP), and social cognition are well-grounded theoretically, most studies have included all male samples, and few have demonstrated consistent effects of either neuropeptide on mentalizing (i.e. understanding the mental states of others). To understand the potential of either neuropeptide as a pharmacological treatment for individuals with impairments in social cognition, it is important to demonstrate the beneficial effects of OT and AVP on mentalizing in healthy individuals. METHODS: In the present randomized, double-blind, placebo-controlled study (n = 186) of healthy individuals, we examined the effects of OT and AVP administration on behavioral responses and neural activity in response to a mentalizing task. RESULTS: Relative to placebo, neither drug showed an effect on task reaction time or accuracy, nor on whole-brain neural activation or functional connectivity observed within brain networks associated with mentalizing. Exploratory analyses included several variables previously shown to moderate OT's effects on social processes (e.g., self-reported empathy, alexithymia) but resulted in no significant interaction effects. CONCLUSIONS: Results add to a growing literature demonstrating that intranasal administration of OT and AVP may have a more limited effect on social cognition, at both the behavioral and neural level, than initially assumed. Randomized controlled trial registrations: ClinicalTrials.gov; NCT02393443; NCT02393456; NCT02394054.

Parsing social motivation: development and validation of a self-report measure of social effort.

BACKGROUND: Reduced efforts to form and maintain social bonds can exist in the context of a sufficient desire for social connection. Thus, social impairment common across many psychiatric conditions may often reflect failures in social effort exertion, despite normative levels of social liking and wanting. Although there are many questionnaires available that assess sociability, desire, or lack thereof for connection and perceived social support, there is no current self-report assessment of the behavioral outputs of social motivation. AIMS: We aimed to develop and validate a measure of the social effort in college students and the general population. METHODS: College students (n = 981) and a broader sample of adults via Amazon's Mechanical Turk (MTurk; n = 506) participated in the study. RESULTS: We identified two factors that represented content related to general social effort and social effort in adherence with social norms; we named the measure the Social Effort and Conscientiousness Scale (SEACS). Results suggest the SEACS is a reliable and valid measure of social effort. CONCLUSIONS: Lower scores on the SEACS were associated with symptoms of depression and anxiety, highlighting the scale's potential utility in clinical populations. We include a discussion of possible applications of the SEACS, including its further use and application in psychopathology research.

Conciliatory gestures promote forgiveness and reduce anger in humans.

Conflict is an inevitable component of social life, and natural selection has exerted strong effects on many organisms to facilitate victory in conflict and to deter conspecifics from imposing harms upon them. Like many species, humans likely possess cognitive systems whose function is to motivate revenge as a means of deterring individuals who have harmed them from harming them again in the future. However, many social relationships often retain value even after conflicts have occurred between interactants, so natural selection has very likely also endowed humans with cognitive systems whose function is to motivate reconciliation with transgressors whom they perceive as valuable and nonthreatening, notwithstanding their harmful prior actions. In a longitudinal study with 337 participants who had recently been harmed by a relationship partner, we found that conciliatory gestures (e.g., apologies, offers of compensation) were associated with increases in victims' perceptions of their transgressors' relationship value and reductions in perceptions of their transgressors' exploitation risk. In addition, conciliatory gestures appeared to accelerate forgiveness and reduce reactive anger via their intermediate effects on relationship value and exploitation risk. These results strongly suggest that conciliatory gestures facilitate forgiveness and reduce anger by modifying victims' perceptions of their transgressors' value as relationship partners and likelihood of recidivism.

Harsh childhood environmental characteristics predict exploitation and retaliation in humans.

Across and within societies, people vary in their propensities towards exploitative and retaliatory defection in potentially cooperative interaction. We hypothesized that this variation reflects adaptive responses to variation in cues during childhood that life will be harsh, unstable and short--cues that probabilistically indicate that it is in one's fitness interests to exploit co-operators and to retaliate quickly against defectors. Here, we show that childhood exposure to family neglect, conflict and violence, and to neighbourhood crime, were positively associated for men (but not women) with exploitation of an interaction partner and retaliatory defection after that partner began to defect. The associations between childhood environment and both forms of defection for men appeared to be mediated by participants' endorsement of a 'code of honour'. These results suggest that individual differences in mutual benefit cooperation are not merely due to genetic noise, random developmental variation or the operation of domain-general cultural learning mechanisms, but rather, might reflect the adaptive calibration of social strategies to local social-ecological conditions.

Cognitive systems for revenge and forgiveness.

Minimizing the costs that others impose upon oneself and upon those in whom one has a fitness stake, such as kin and allies, is a key adaptive problem for many organisms. Our ancestors regularly faced such adaptive problems (including homicide, bodily harm, theft, mate poaching, cuckoldry, reputational damage, sexual aggression, and the infliction of these costs on one's offspring, mates, coalition partners, or friends). One solution to this problem is to impose retaliatory costs on an aggressor so that the aggressor and other observers will lower their estimates of the net benefits to be gained from exploiting the retaliator in the future. We posit that humans have an evolved cognitive system that implements this strategy ­ deterrence ­ which we conceptualize as a revenge system. The revenge system produces a second adaptive problem: losing downstream gains from the individual on whom retaliatory costs have been imposed. We posit, consequently, a subsidiary computational system designed to restore particular relationships after cost-imposing interactions by inhibiting revenge and motivating behaviors that signal benevolence for the harmdoer. The operation of these systems depends on estimating the risk of future exploitation by the harmdoer and the expected future value of the relationship with the harmdoer. We review empirical evidence regarding the operation of these systems, discuss the causes of cultural and individual differences in their outputs, and sketch their computational architecture.

Putting revenge and forgiveness in an evolutionary context.

In this response, we address eight issues concerning our proposal that human minds contain adaptations for revenge and forgiveness. Specifically, we discuss (a) the inferences that are and are not licensed by patterns of contemporary behavioral data in the context of the adaptationist approach; (b) the theoretical pitfalls of conflating proximate and ultimate causation; (c) the role of development in the production of adaptations; (d) the implications of proposing that the brain's cognitive systems are fundamentally computational in nature; (e) our preferred method for considering the role of individual differences in computational systems; (f) applications of our proposal to understanding conflicts between groups; (g) the possible implications of our views for understanding the operation of contemporary criminal justice systems; and (h) the question of whether people ever "genuinely" forgive.

Initial evidence for a relation between behaviorally assessed empathic accuracy and affect sharing for people and music.

Are people who are better able to understand or feel the emotions of others also better at understanding or feeling emotions conveyed through music? Although evolutionary theories have proposed that both empathy and music help to foster social connection, few studies to date have examined the relation between behavioral assessments of empathic processes for people and music. We examined this question using 2 independent samples: a laboratory sample of undergraduates (n = 236) and a larger online direct replication with participants across the United States (n = 596). Across both samples, linear mixed effects models showed positive associations between empathic accuracy and affect sharing for people telling personal stories and for musical expression, and results were maintained when including relevant individual differences as covariates. These findings provide initial evidence of a relation between behaviorally assessed empathic processes across social and musical domains. Future research is needed to build upon this evidence by investigating whether active, socially engaged music listening may have a beneficial effect on social cognition. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Conciliatory gestures facilitate forgiveness and feelings of friendship by making transgressors appear more agreeable.

The authors examined how conciliatory gestures exhibited in response to interpersonal transgressions influence forgiveness and feelings of friendship with the transgressor. In Study 1, 163 undergraduates who had recently been harmed were examined longitudinally. Conciliatory gestures exhibited by transgressors predicted higher rates of forgiveness over 21 days, and this relationship was mediated by victims' perceptions of their transgressors' Agreeableness. Study 2 was an experiment including 145 undergraduates who experienced a breach in trust from an anonymous partner during an iterated prisoner's dilemma. When transgressors apologized and offered financial compensation, participants reported higher levels of forgiveness and feelings of friendship when compared to a control condition and an aggravating condition. The effects of apology/compensation on forgiveness and perceived friendship were mediated by victims' perceptions of their transgressors' Agreeableness. Results suggest that conciliatory gestures promote forgiveness in part by depicting transgressors as more sympathetic, considerate, fair, and just (i.e., agreeable).

The pandemic should catalyze research on social pain: Examining oxytocin administration studies.

For decades, researchers have tried to identify drugs that can decrease the painful feelings associated with social loss, rejection, or isolation. One effort has been to investigate whether the neuropeptide oxytocin reduces social pain. In this commentary, I examine intranasal oxytocin's effects on experimentally induced social exclusion. Future recommendations are presented with the goal of spurring new research efforts to elucidate the neurobiological mechanisms underlying the experience of social pain.

Social anxiety and behavioral assessments of social cognition: A systematic review.

BACKGROUND: Social anxiety is highly prevalent and has increased in young adults during the COVID-19 pandemic. Since social anxiety negatively impacts interpersonal functioning, identifying aspects of social cognition that may be impaired can increase our understanding of the development and maintenance of social anxiety disorder. However, to date, studies examining associations between social anxiety and social cognition have resulted in mixed findings. METHODS: The aim of this systematic review was to summarize the literature on the association between social anxiety and social cognition, while also considering several potential moderators and covariates that may influence findings. RESULTS: A systematic search identified 52 studies. Results showed mixed evidence for the association between social anxiety and lower-level social cognitive processes (emotion recognition and affect sharing) and a trend for a negative association with higher-level social cognitive processes (theory of mind and empathic accuracy). Most studies examining valence-specific effects found a significant negative association for positive and neutral stimuli. LIMITATIONS: Not all aspects of social cognition were included (e.g., attributional bias) and we focused on adults and not children, limiting the scope of the review. CONCLUSIONS: Future studies would benefit from the inclusion of relevant moderators and covariates, multiple well-validated measures within the same domain of social cognition, and assessments of interpersonal functioning outside of the laboratory. Additional research examining the moderating role of attention or interpretation biases on social cognitive performance, and the potential benefit of social cognitive skills training for social anxiety, could inform and improve existing cognitive behavioral interventions.

Social anxiety is associated with greater peripheral oxytocin reactivity to psychosocial stress.

To date, it has been difficult to establish reliable biomarkers associated with specific forms of psychopathology. Social anxiety, for example, is associated with inconsistent biological responses to psychosocial stress on markers including cortisol and salivary alpha-amylase. Thus, it is critical that studies identify more reliable biomarkers that index patterns associated with social anxiety. Two potential candidates are the neuropeptides oxytocin and vasopressin, which have been implicated in stress responsivity across species. Studies have demonstrated a reliable increase in oxytocin, and a surrogate marker for vasopressin, following engagement in the most widely used lab-based psychosocial stress paradigm: the Trier Social Stress Test (TSST). However, no study has examined whether social anxiety moderates peripheral oxytocin or vasopressin reactivity to psychosocial stress. In 101 young adult participants, dimensionally assessed social anxiety was associated with greater plasma oxytocin, but not vasopressin, reactivity to the TSST. Results were maintained following the inclusion of depression as a covariate. Findings suggest that studying changes in peripheral oxytocin concentrations may be a method of differentiating individuals with higher levels of social anxiety.

Revisiting the association between self-reported empathy and behavioral assessments of social cognition.

Previous research has shown a weak association between self-reported empathy and performance on behavioral assessments of social cognition. However, previous studies have often overlooked important distinctions within these multifaceted constructs (e.g., differences among the subcomponents of self-reported empathy, distinctions in tasks assessing lower- vs. high-level social cognition, and potential covariates that represent competing predictors). Using data from three separate studies (total N = 2,376), we tested whether the tendency to take the perspective of others (i.e., perspective-taking), and the tendency to catch the emotions of others (i.e., emotional contagion for positive and negative emotions), were associated with performance on tasks assessing lower- to higher-level social-cognitive ability (i.e., emotion recognition, theory of mind, and empathic accuracy) and affect sharing. Results showed little evidence of an association between any of the self-reported empathy measures and either social-cognitive ability or affect sharing. Using several large samples, our findings add additional evidence to previous work showing that self-report measures of empathy are not valid proxies of behaviorally assessed social cognition. Moreover, we find that the ease with which individuals recognize and understand their own emotions (i.e., alexithymia) is more related to social-cognitive abilities and affect sharing, than their tendency to take the perspective of others, or to vicariously experience the emotions of others. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Oxytocin reactivity to a lab-based stressor predicts support seeking after stress in daily life: Implications for the Tend-and-Befriend theory.

Social relationships play an important role in mental and physical health, particularly during times of stress. However, little is known about the biological mechanisms underlying the tendency to seek support following stress. The Tend-and-Befriend theory suggests that oxytocin (OT) may enhance the desire for social contact in response to stress. Yet, no studies in humans have provided empirical support for the connection between stress-induced changes in endogenous OT and increased support seeking after stress. In the present study, 94 participants performed a standardized laboratory stressor and then completed two weeks of daily assessments of support seeking after stress. In line with preregistered hypotheses, stress-induced plasma OT reactivity to the laboratory stressor was associated with more frequent support seeking behaviors following stress in daily life (i.e., outside of the laboratory). Additional results suggested that attachment anxiety (but not avoidance) strengthened this association. Our findings implicate the OT system in affiliative behaviors following stress, providing empirical support for the Tend-and-Befriend theory.

Evaluation of enzyme immunoassay and radioimmunoassay methods for the measurement of plasma oxytocin.

OBJECTIVE: There is increased interest in measuring peripheral oxytocin levels to better understand the role of this peptide in mammalian behavior, physiology, and disease. The purpose of this study was to compare methods for plasma oxytocin measurement using a commercially available enzyme immunoassay (EIA) and radioimmunoassay (RIA), to evaluate the need for sample extraction, and to assess the immunospecificity of the assays. METHODS: Oxytocin was measured in extracted and unextracted human plasma samples (n = 39). Oxytocin and its degradation products were separated by high-performance liquid chromatography and gel filtration chromatography and then assayed by EIA or RIA to identify oxytocin immunoreactive peaks. RESULTS: Without extraction, plasma measured by EIA was more than 100-fold higher than in extracted plasma, and the correlation between oxytocin levels in extracted and unextracted plasma was minimal (Spearman ρ = -0.10, p = .54). Using the RIA, most samples (>90%) were below the level of detection with or without extraction. After chromatographic fractionation of sample extracts, multiple immunoreactive products were found to be present in addition to oxytocin, which casts doubts on the specificity of the assays. CONCLUSIONS: Changes in oxytocin levels have been reported in social and behavioral challenge studies. This study indicates that sample extraction is necessary to obtain valid assay results. Changes in oxytocin degradation products are likely to contribute to the previously observed responses in circulating oxytocin levels to behavioral and social challenge. There is a critical need for valid and reliable methods to measure oxytocin in biologic samples.

Social anxiety is negatively associated with theory of mind and empathic accuracy.

Social anxiety interferes with accurate perceptions of others' thoughts and intentions, yet studies examining the association between social anxiety and social cognition have resulted in mixed findings. We examined the association between dimensional levels of social anxiety and assessments of lower- and higher-level social cognition. In Study 1 (n = 1485), we found that social anxiety was negatively related to accuracy in an assessment of higher-level social cognition (i.e., theory of mind) across all stimuli. However, no consistent association was found between social anxiety and accuracy in an assessment of lower-level social cognition (i.e., emotion recognition). In Study 2 (n = 363), we found that social anxiety was negatively associated with another higher-level form of social cognition, empathic accuracy, for positive but not negative stimuli. These findings demonstrate that social anxiety is negatively associated with higher-level social cognition but not lower-level social cognition, and this association appears to be more consistent for positive stimuli. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Preliminary Evidence That CD38 Moderates the Association of Neuroticism on Amygdala-Subgenual Cingulate Connectivity.

CD38 genetic variation has been associated with autism spectrum disorders and social anxiety disorder, which may result from CD38's regulation of oxytocin secretion. Converging evidence has found that the rs3796863 A-allele contributes to increased social sensitivity compared to the CC genotype. The current study examined the moderating role of CD38 genetic variants (rs3796863 and rs6449182) that have been associated with enhanced (or reduced) social sensitivity on neural activation related to neuroticism, which is commonly elevated in individuals with social anxiety and depression. Adults (n = 72) with varying levels of social anxiety and depression provided biological samples for DNA extraction, completed a measure of neuroticism, and participated in a standardized emotion processing task (affect matching) while undergoing fMRI. A significant interaction effect was found for rs3796863 x neuroticism that predicted right amygdala-subgenual anterior cingulate cortex (sgACC) functional connectivity. Simple slopes analyses showed a positive association between neuroticism and right amygdala-sgACC connectivity among rs3796863 A-allele carriers. Findings suggest that the more socially sensitive rs3796863 A-allele may partially explain the relationship between a known risk factor (i.e. neuroticism) and promising biomarker (i.e. amygdala-sgACC connectivity) in the development and maintenance of social anxiety and depression.

Null results of oxytocin and vasopressin administration across a range of social cognitive and behavioral paradigms: Evidence from a randomized controlled trial.

Research examining oxytocin and vasopressin in humans has the potential to elucidate neurobiological mechanisms underlying human sociality that have been previously unknown or not well characterized. A primary goal of this work is to increase our knowledge about neurodevelopmental and psychiatric disorders characterized by impairments in social cognition. However, years of research highlighting wide-ranging effects of, in particular, intranasal oxytocin administration have been tempered as the fields of psychology, neuroscience, and other disciplines have been addressing concerns over the reproducibility and validity of research findings. We present a series of behavioral tasks that were conducted using a randomized, double-blind, placebo controlled, between-subjects design, in which our research group found no main effects of oxytocin and vasopressin on a host of social outcomes. In addition to null hypothesis significance testing, we implemented equivalence testing and Bayesian hypothesis testing to examine the sensitivity of our findings. These analyses indicated that 47-83% of our results (depending on the method of post-hoc analysis) had enough sensitivity to detect the absence of a main effect. Our results add to evidence that intranasal oxytocin may have a more limited direct effect on human social processes than initially assumed and suggest that the direct effects of intranasal vasopressin may be similarly limited. Randomized controlled trial registration: NCT01680718.

Sensing emotion in voices: Negativity bias and gender differences in a validation study of the Oxford Vocal ('OxVoc') sounds database.

Emotional expressions are an essential element of human interactions. Recent work has increasingly recognized that emotional vocalizations can color and shape interactions between individuals. Here we present data on the psychometric properties of a recently developed database of authentic nonlinguistic emotional vocalizations from human adults and infants (the Oxford Vocal 'OxVoc' Sounds Database; Parsons, Young, Craske, Stein, & Kringelbach, 2014). In a large sample (n = 562), we demonstrate that adults can reliably categorize these sounds (as 'positive,' 'negative,' or 'sounds with no emotion'), and rate valence in these sounds consistently over time. In an extended sample (n = 945, including the initial n = 562), we also investigated a number of individual difference factors in relation to valence ratings of these vocalizations. Results demonstrated small but significant effects of (a) symptoms of depression and anxiety with more negative ratings of adult neutral vocalizations (R2 = .011 and R2 = .008, respectively) and (b) gender differences in perceived valence such that female listeners rated adult neutral vocalizations more positively and infant cry vocalizations more negatively than male listeners (R2 = .021, R2 = .010, respectively). Of note, we did not find evidence of negativity bias among other affective vocalizations or gender differences in perceived valence of adult laughter, adult cries, infant laughter, or infant neutral vocalizations. Together, these findings largely converge with factors previously shown to impact processing of emotional facial expressions, suggesting a modality-independent impact of depression, anxiety, and listener gender, particularly among vocalizations with more ambiguous valence. (PsycINFO Database Record

Oxytocin, but not vasopressin, impairs social cognitive ability among individuals with higher levels of social anxiety: a randomized controlled trial.

Individuals with social anxiety are characterized by a high degree of social sensitivity, which can coincide with impairments in social cognitive functioning (e.g. theory of mind). Oxytocin (OT) and vasopressin (AVP) have been shown to improve social cognition, and OT has been theorized as a potential therapeutic agent for individuals with social anxiety disorder. However, no study has investigated whether these neuropeptides improve social cognitive ability among socially anxious individuals. In a randomized, double-blind, placebo controlled, between-subjects design we investigated whether social anxiety moderated the effects of OT or AVP (vs placebo) on social working memory (i.e. working memory that involves manipulating social information) and non-social working memory. OT vs placebo impaired social working memory accuracy in participants with higher levels of social anxiety. No differences were found for non-social working memory or for AVP vs placebo. Results suggest that OT administration in individuals with higher levels of social anxiety may impair social cognitive functioning. Randomized-controlled trial registration: NCT01680718.