Intranasal Oxytocin Differentially Affects Functional Connectivity in Women with and without Autism

Background: Oxytocin, which is known to influence social behaviour and cognition, may be of therapeutic value for enhancing social functioning in individuals with autism spectrum conditions (ASC). We previously reported that intranasal oxytocin increased resting state connectivity across subcortical and cortical networks in neurotypical women and that this effect correlated positively with autistic-like traits [1]. Thus, we predicted strong oxytocin-induced increases in functional connectivity in the same corticostriatal circuit in women with ASC.

Objectives: To test whether the same effect of oxytocin on resting state connectivity observed in neurotypical women is present in autistic women.

Methods: To extend this study, 16 age- and IQ-matched women with a diagnosis of high-functioning autism or Asperger syndrome participated in the same double-blind placebo-controlled crossover experiment. Resting-state functional magnetic resonance imaging (fMRI) data were collected after intranasal administration of 24 IU oxytocin (Syntocinon, Novartis) or placebo. A total of 270 resting-state functional volumes (eyes-open, with fixation cross) were acquired using a multi-echo sequence and online reconstruction (TR = 2300 ms; field-of-view = 240 mm; 33 oblique slices, alternating slice acquisition, slice thickness = 3.8 mm, 11% slice gap; 3 echoes at TE = 12, 29, and 46 ms, flip angle 80°). Independent components analysis was applied to examine connectivity between networks. Correlation matrices for all independent component (IC) pairs were computed with corrections for multiple comparisons.

Results: Mirroring our previous finding, we identified components involved in reward, emotion, social communication, language, and pain processing. Three IC pairs showed significant changes in activation between the oxytocin and placebo conditions in autistic women, although the effect sizes were small (≤0.80, Cohen’s d). The independent component pair (IC11-IC21) previously found to show the greatest oxytocin-induced connectivity increase in neurotypical women did not show a significant connectivity change between placebo and oxytocin conditions in autistic women. While all neurotypical women showed significantly increased connectivity in this IC pair under oxytocin relative to placebo, several autistic women showed a substantial decrease in connectivity under the oxytocin condition (Figure 1). Overall, oxytocin-induced connectivity changes were more heterogeneous in autistic women compared to neurotypical women.

Conclusions: These findings are suggestive that response to exogenous oxytocin between autistic and neurotypical women. Within the autism group, individual differences in response to oxytocin may arise from differences in the oxytocinergic system or interactions between oxytocin and other hormones. In future work, we plan we explore this possibility by combining fMRI data and salivary hormone level data.

1. Bethlehem, RAI et al. Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women. Transl Psychiatry (2017).