The social effects of intranasal oxytocin reported in all-male samples may not generalize to females.Neuroimaging studies reliably demonstrate opposing effects of oxytocin on the activation of social ...brain regions – particularly the amygdala – in males and females.Sex differences in the effects of oxytocin on social cognition and behavior are context-dependent, with more reports of 'prosocial' effects in males.Sex-differential effects may arise from differences in the underlying physiology (endogenous oxytocin system variation, multi-hormone interactions) and/or socialization processes, reflecting the role of oxytocin in promoting evolutionarily adaptive social interactions and/or sociocultural processes such as gender roles.Oxytocin cannot be assumed to influence social outcomes in a 'one-size-fits-all' manner: individual differences such as sex and social context must be considered.
Although the social role of oxytocin came to light due to sex-specific interactions such as mother–offspring bonding, current understanding of sex differences in the effects of oxytocin on human sociality is limited because of the predominance of all-male samples. With the increasing inclusion of females in intranasal oxytocin research, it is now possible to explore such patterns. Neuroimaging studies reveal relatively consistent sex-differential effects of oxytocin on the activation of brain regions associated with processing social stimuli – particularly the amygdala. Findings from behavioral research are varied but suggest that oxytocin more often facilitates social cognition and positive social interactions in males, with context-dependent effects in each sex. We discuss potential biological and psychological mechanisms underlying the reported sex differences, and conclude with considerations for future research and clinical applications of oxytocin.
Although the social role of oxytocin came to light due to sex-specific interactions such as mother–offspring bonding, current understanding of sex differences in the effects of oxytocin on human sociality is limited because of the predominance of all-male samples. With the increasing inclusion of females in intranasal oxytocin research, it is now possible to explore such patterns. Neuroimaging studies reveal relatively consistent sex-differential effects of oxytocin on the activation of brain regions associated with processing social stimuli – particularly the amygdala. Findings from behavioral research are varied but suggest that oxytocin more often facilitates social cognition and positive social interactions in males, with context-dependent effects in each sex. We discuss potential biological and psychological mechanisms underlying the reported sex differences, and conclude with considerations for future research and clinical applications of oxytocin.
Oxytocin and testosterone coordinate adaptive social behaviors with stimuli in the environment. Administration of oxytocin and testosterone is associated with increased and reduced indicators of ...empathy, respectively, but how levels of these hormones are jointly affected by naturalistic empathy-inducing stimuli remains unclear. In this study, salivary oxytocin and testosterone levels were measured in 173 healthy adults before and after watching a video involving a gravely ill child. Participants also completed questionnaires to assess psychological variables predicted to affect oxytocin reactivity (Autism-Spectrum Quotient, Interpersonal Reactivity Index, Empathy and Systemizing Quotients). On average, there was a 14% increase in oxytocin (p = 0.003) and 4% decrease in testosterone (p = 0.001) pre- to post-video. Opposite directional changes in hormone levels occurred together, as supported by a chi-square test (p < 0.001) and a circular statistics test (p < 0.05). Considered separately, psychological traits did not predict hormone levels or changes to any appreciable degree. However, oxytocin and testosterone changes were linked with empathy relative to systemizing such that: (1) ‘Empathy Bias’ was associated with a large oxytocin increase but little change in testosterone, while (2) ‘Systemizing Bias’ and ‘Balance’ between empathy and systemizing were associated with a decrease in testosterone but little change in oxytocin. These findings suggest that participants were divisible into ‘high oxytocin responders’ (relatively empathetic) and ‘high testosterone responders’ (balanced or systemizing-biased). These findings support a model of joint, opposite changes in oxytocin and testosterone under experimental empathy induction, with high, somewhat predictable, diversity in individual responses.
•Oxytocin levels increased, and testosterone decreased, after empathy induction.•These hormonal shifts were affected by self-reported empathizing and systemizing.•Oxytocin and testosterone thus show antagonistic effects, mediated by personality.
Genetic variation in CD38-a putative oxytocin pathway gene-has been linked to higher oxytocin levels, empathy, and sensitive parenting, but also to more negative interpersonal outcomes (e.g., ...alienation from friends and family, poorer romantic relationship quality). To reconcile these seemingly contradictory findings, we drew upon the idea that CD38 variation may heighten social-emotional sensitivity and, consequently, make individuals prone to negative emotions in distressing interpersonal situations. To test this hypothesis, we performed a secondary analysis of a dataset including participants' (n = 171; 94 females) empathic concern ("sympathetic") and distress-related ("anxious") responses to an emotional video. Distress responses were higher for the CD38 rs3796863 AA/AC group vs. the CC group (p = 0.03, η
= 0.027); however, there was no significant effect of genotype for empathic concern responses to the video or for indices of trait empathy. These findings provide preliminary evidence that, in the face of an interpersonal stressor, CD38 genetic variation may predict more self-focused, aversive emotional reactions. More broadly, this finding highlights the need to adopt a more nuanced perspective in which the influence of oxytocin system variation (assessed by oxytocin-related genetic variation) should be considered in light of the social context.
Perspectives on autism and psychiatric conditions are affected by a mix of scientific and social influences. Evolutionary psychiatry (EP) and the neurodiversity movement are emerging paradigms that ...reflect these distinct influences, with the former grounded in scientific theory and the latter driven by political and social principles. Despite their separate foundations, there is a significant overlap between EP and neurodiversity that has not been explored. Specifically, both paradigms reframe disorders as natural cognitive differences rather than disease; expand the concept of "normal" beyond that implied in modern psychiatry; focus on relative strengths; recognize that modern environments disadvantage certain individuals to cause functional impairment; emphasize cognitive variation being socially accommodated and integrated rather than treated or cured; and can help reduce stigmatization. However, in other ways, they are distinct and sometimes in conflict. EP emphasizes scientific explanation, defines "dysfunction" in objective terms, and differentiates heterogenous cases based on underlying causes (e.g. autism due to de novo genetic mutations). The neurodiversity movement emphasizes social action, removes barriers to inclusion, promotes inclusive language, and allows unrestricted identification as neurodivergent. By comparing and contrasting these two approaches, we find that EP can, to some extent, support the goals of neurodiversity. In particular, EP perspectives could be convincing to groups more responsive to scientific evidence and help achieve a middle ground between neurodiversity advocates and critics of the movement.
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•We review the biological bases for low social anxiety in Williams syndrome.•Oxytocin and the GTF2I gene mediate copy number phenotypes for this region.•GTF2I polymorphisms and gene ...deletion influence oxytocin reactivity.•GTF2I, and oxytocin production, are subject to parent of origin effects.•Williams syndrome may reflect, in part, the active but odd’ subtype of autism.
We describe and evaluate an integrative hypothesis for helping to explain the major neurocognitive features of individuals with Williams syndrome region deletions and duplications. First, we demonstrate how the cognitive differences between Williams syndrome individuals, individuals with duplications of this region, and healthy individuals parallel the differences between individuals subject to effects of increased or decreased oxytocin. Second, we synthesize evidence showing that variation in expression of the gene GTF2I (General Transcription Factor II–I) underlies the primary social phenotypes of Williams syndrome and that common genetic variation in GTF2I mediates oxytocin reactivity, and its correlates, in healthy populations. Third, we describe findings relevant to the hypothesis that the GTF2I gene is subject to parent of origin effects whose behavioral expression fits with predictions from the kinship theory of genomic imprinting. Fourth, we describe how Williams syndrome can be considered, in part, as an autistic syndrome of Lorna Wing's ‘active-but-odd' autism subtype, in contrast to associations of duplications with both schizophrenia and autism.
Little is known about the neurobiological pathways through which testosterone promotes aggression or about the people in whom this effect is observed. Using a psychopharmacogenetic approach, we found ...that testosterone increases aggression in men (N = 308) with select personality profiles and that these effects are further enhanced among those with fewer cytosine-adenine-guanine (CAG) repeats in exon 1 of the androgen receptor (AR) gene, a polymorphism associated with increased AR efficiency. Testosterone’s effects were rapid (~30 min after administration) and mediated, in part, by subjective reward associated with aggression. Testosterone thus appears to promote human aggression through an AR-related mechanism and to have stronger effects in men with the select personality profiles because it more strongly upregulates the subjective pleasure they derive from aggression. Given other evidence that testosterone regulates reward through dopaminergic pathways, and that the sensitivity of such pathways is enhanced among individuals with the personality profiles we identified, our findings may also implicate dopaminergic processes in testosterone’s heterogeneous effects on aggression.
The social heuristic hypothesis posits that human cooperation is an intuitive response that is expressed especially under conditions of time-constraint. Conversely, it proposes that for individuals ...given an opportunity for reflection, cooperation is more likely to be curtailed by an optimizing process calibrated to maximize individual benefit in a given situation. Notably, the steroid hormone testosterone has also been implicated in intuitive decision-making, including both prosocial and anti-social behaviors, with effects strongest in men with particular dispositional characteristics. This raises the possibility that increased testosterone may augment the effects predicted by the social heuristic hypothesis, particularly among men higher in specific dispositional characteristics (dominance, impulsivity, independent self-construal: high risk for testosterone-induced antisocial behavior). Here, in a testosterone administration study with a relatively large sample of men (N = 400), we test this possibility in a double-blind, placebo-controlled paradigm, with men randomly assigned to play a one-shot public goods game either under time-pressure (forced intuition) or with a time delay (forced reflection). Results revealed that within the placebo group, time-pressure (versus forced delay) increased cooperation among low risk men, but decreased cooperation among high risk men. Testosterone further moderated this pattern by abolishing the time-pressure effect in low risk men and-in high risk men-reversing the effect by selectively reducing offers (compared to placebo) under forced delay. This is the first evidence that testosterone and personality can interact with time-pressure and delay to predict human cooperation.
The neurohormone oxytocin plays a central role in human social behaviour and cognition, and oxytocin dysregulation may contribute to psychiatric disorders. However, genetic factors influencing ...individual variation in the oxytocinergic system remain poorly understood. We genotyped 169 healthy adults for a functional polymorphism in GTF2I (general transcription factor II-I), a gene associated with high prosociality and reduced social anxiety in Williams syndrome, a condition reported to involve high oxytocin levels and reactivity. Participants’ salivary oxytocin levels were measured before and after watching a validated empathy-inducing video. Oxytocin reactivity, defined as pre- to post-video percentage change in salivary oxytocin, varied substantially and significantly between individuals with different GTF2I genotypes, with, additionally, a trend towards an interaction between genotype and sex. Individuals with more oxytocin-reactive genotypes also reported significantly lower social anxiety. These findings suggest a model whereby GTF2I has a continuum of effects on human sociality, from the extreme social phenotypes and oxytocin dysregulation associated with gene deletion in Williams syndrome, to individual differences in oxytocin reactivity and sociality associated with common polymorphisms in healthy populations.
Oxytocin is hypothesized to promote social interactions by enhancing the salience of social stimuli. While previous neuroimaging studies have reported that oxytocin enhances amygdala activation to ...face stimuli in autistic men, effects in autistic women remain unclear. In this study, the influence of intranasal oxytocin on activation and functional connectivity of the basolateral amygdala--the brain's 'salience detector'--while processing emotional faces vs shapes was tested in 16 autistic and 21 non-autistic women by functional magnetic resonance imaging in a placebo-controlled, within-subject, cross-over design. In the placebo condition, minimal activation differences were observed between autistic and non-autistic women. However, significant drug * group interactions were observed for both basolateral amygdala activation and functional connectivity. Oxytocin increased left basolateral amygdala activation among autistic women (35-voxel cluster, Montreal Neurological Institute (MNI) coordinates of peak voxel = -22 -10 -28; mean change = +0.079%, t = 3.159, P.sub.Tukey = 0.0166) but not among non-autistic women (mean change = +0.003%, t = 0.153, P.sub.Tukey = 0.999). Furthermore, oxytocin increased functional connectivity of the right basolateral amygdala with brain regions associated with socio-emotional information processing in autistic women, but not in non-autistic women, attenuating group differences in the placebo condition. Taken together, these findings extend evidence of oxytocin's effects on the amygdala to specifically include autistic women and specify the subregion of the effect.
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