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.

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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 (), 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 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 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.

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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 timepressure and delay to predict human cooperation.Effect of exogenous testosterone on cooperation depends on personality. . . BM Bird et al.Neuropsychopharmacology (2019) 44:538 -545 1234567890();,:Effect of exogenous testosterone on cooperation depends on personality. . . BM Bird et al.

Variation in the AVPR1a gene, which codes for a receptor for the neurohormone vasopressin, has been found to relate to autism risk. Interestingly, variation in this gene also relates to differences in social behaviour in non-clinical populations. Variation in this gene may affect expression of AVPR1a receptors in brain areas involved in social behaviour. Here, we tested whether AVPR1a variation was associated with Autism Quotient (AQ) scores, a questionnaire that measures non-clinical manifestations of autism, in a population of 873 healthy university students. The AVPR1a RS1 and RS3 microsatellites were examined, and variants were categorized as "long" or "short". The RS3 long/long genotype was significantly associated with a higher AQ score (i.e., a more autistic-like phenotype) for the combined population and for females only. Further examination showed that this relationship was due to a specific RS3 variant, termed the "target allele", which previous research has linked to reduced altruism and increased marital problems in healthy individuals. We also observed that the relationship between RS3 genotype and AQ score was mainly due to the "attention switching" (the ability to shift attention from one task to another) component of the questionnaire; this ability is commonly impaired in autism spectrum disorders. Overall, our study establishes continuity between the existing AVPR1a research in clinical and non-clinical populations. Our results suggest that vasopressin may exert its effects on social behaviour in part by modulating attentional focus between social and non-social cues. Autism Res 2017, 10: 750-756. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Background: Oxytocin administration, which may be of therapeutic value for individuals with social difficulties, is likely to affect endogenous levels of other socially relevant hormones. However, to date, the effects of oxytocin administration on endogenous hormones have only been examined in neurotypical individuals. The need to consider multi-hormone interactions is particularly warranted in oxytocin trials for autism due to evidence of irregularities in both oxytocin and sex steroid systems. Methods: In this double-blind cross-over study, saliva samples were collected from 16 autistic and 29 neurotypical women before and after intranasal administration of 24 IU oxytocin or placebo. Oestradiol, testosterone, and oxytocin levels were quantified in saliva samples. Participants also completed the Autism-Spectrum Quotient (AQ) and Empathy Quotient (EQ) questionnaires. Results: Distinct patterns of change in testosterone and oestradiol levels pre-to-post-administration were observed in autistic relative to neurotypical women (ANCOVA, p < 0.05 main effect of Group), controlling for sample collection time. The mean percent change oestradiol was + 8.8% for the autism group and − 13.0% for the neurotypical group (t = 1.81, p = 0.08), while the mean percent change testosterone was + 1.1% in the autism group and − 12.6% in the neurotypical group (t = 1.26, p = 0.22). In the oxytocin condition, the mean percent change oestradiol was + 12.6% in the autism group and − 6.9% in the neurotypical group (t = 1.78, p = 0.08), while the mean percent change testosterone was + 14.4% in the autism group and − 15.2% in the neurotypical group (t = 3.00, p = 0.006). Robust regression confirmed that group differences in percent change hormone levels were not driven by a small number of influential individuals. Baseline hormone levels did not differ between groups when considered individually. However, baseline testosterone relative to oestradiol (T:E2 ratio) was higher in autistic women (p = 0.023, Cohen's d = 0.63), and this ratio correlated positively and negatively with AQ and EQ scores, respectively, in the combined sample. Limitations: Further studies with larger and more diverse autistic sample are warranted to confirm these effects.

Intranasal oxytocin administration has been shown to influence a variety of outcomes related to social behavior and cognition in clinical and typical samples. One possibility for these diverse effects is that oxytocin alters functional connectivity of social brain regions. However, this hypothesis has not been tested in autistic women. Using a cross-over design, we examined the effects of a single 24IU dose of oxytocin relative to placebo on resting-state functional connectivity in 16 autistic women and 23 non-autistic women matched for age and IQ. Connectivity among social brain regions (amygdala, anterior cingulate cortex (ACC), insula, medial prefrontal cortex (mPFC), and temporoparietal junction (TPJ)) was examined and compared between drug conditions and groups. We found a main drug effect for ACC-insula connectivity, with lower mean connectivity in the oxytocin condition. Significant Drug×Group interactions were also observed, such that oxytocin tended to increase connectivity among amygdala, insula, mPFC, and TPJ in autistic women but decrease connectivity in non-autistic women. Among autistic women, oxytocin-associated increases of moderate effect size were observed for insula-left TPJ and left amygdala-right TPJ connectivity, which attenuated large group connectivity differences observed in the baseline condition. Exploratory analyses suggested that women whose salivary oxytocin levels were more elevated from baseline by oxytocin administration tended to show larger increases in connectivity. These findings offer further evidence that oxytocin influences resting-state connectivity, with effects moderated by individual differences in endogenous hormone levels and clinical phenotype.