Effects of oxytocin on the social brain in autistic and typical women

Chapter 1 of this work introduces the neurohormone oxytocin, its roles in social behaviour and cognition, and its associations with autism. Oxytocin is then discussed as one of the few compounds to have shown effects for the core social challenges of autism, and the gaps in knowledge that have hindered therapeutic applications of oxytocin are described. Specifically, uncertainty regarding the neural mechanisms through which oxytocin influences social behaviour and the inconsistent patterns of oxytocin’s effects across studies are noted. Chapter 2 presents a systematic review of the oxytocin administration literature to identify variables shown to influence individual differences in response to oxytocin, including biological sex, oxytocin-related genotype, and broader autism phenotype. Chapters 3 to 6 report the findings of a double-blind, placebo-controlled oxytocin administration experiment involving 42 adult women, 16 of whom have an autism diagnosis. Chapter 3 reports pre- to-post administration changes in participants’ salivary hormone levels and tests relationships between baseline hormone levels and psychological traits. An increase in salivary testosterone after oxytocin administration was observed in autistic women, but not in non-autistic women, and autistic-like traits correlated positively with greater testosterone relative to oestradiol. In Chapter 4, fMRI is used to assess the effects of oxytocin on resting-state connectivity. In the placebo condition, autistic women showed lower resting-state connectivity among social brain areas compared to non-autistic women. At the group level, oxytocin enhanced connectivity among autistic women, but decreased connectivity among non-autistic women, such that average connectivity in autistic women in the oxytocin condition resembled that in non-autistic women in the placebo condition. Chapter 5 reports the effects of oxytocin on activation of the amygdala, a brain region implicated in autism and emotional response, while matching images of negatively-valenced face stimuli (Hariri task). Matching faces (relative to matching shapes) robustly activated bilateral amygdala in both groups. Oxytocin was found to increase amygdala activation to face stimuli in autistic women and to enhance amygdala functional connectivity in the combined sample. Chapter 6 presents the effects of oxytocin on neural reward processing during two variants of an incentive delay task: one involving a social reward (a smiling face) and one involving a non-social reward (money). Autistic women showed lower activation of brain areas associated with reward anticipation relative to non-autistic women. Oxytocin increased activation of the same regions, with variation by group, task phase (anticipation vs outcome), and reward type. The discussion in Chapter 7 ties the findings of the multiple neuroimaging studies together, suggesting that oxytocin influences several neural pathways expected to influence social behaviour and cognition. The general patterns of how individual differences, including autism phenotype and social traits, influenced the effects of oxytocin on brain activation and the implications for therapeutic applications of oxytocin are also discussed. Finally, the limitations of these studies and directions for future research in this area are addressed