µ-Opioid Modulation of Sensorimotor Functional Connectivity in Autism: Insights from a Pharmacological Neuroimaging Investigation using Tianeptine

Reproducible patterns of atypical functional connectivity of sensorimotor and higher-order networks have been previously identified in the autistic brain. However, the neurosignalling pathways underpinning these differences remain unclear. The µ-opioid system is involved in sensory processing as well as social and reward behaviours and has been implicated in autism, suggesting a potential role in shaping the autistic brain. Hence, we tested the hypothesis that there is atypical involvement of the µ-opioid system in these networks in autism. We used a placebo-controlled, double-blind, randomised, crossover study design to compare the effects of an acute dose of the µ-opioid receptor agonist tianeptine in autistic and non-autistic participants on functional connectivity (FC) of sensorimotor and frontoparietal networks. We found that tianeptine increased FC of a sensorimotor network previously characterised by atypically low FC in autism. The connectivity of the frontoparietal network was not significantly shifted. Our findings suggest that µ-opioid neurosignalling might contribute to functional brain differences in the sensorimotor network in autism. Given that sensorimotor system alterations are thought to be core to autism and contribute to other core autistic features, as well as adaptability and mental health, further research is warranted to explore the translational potential of µ-opioid modulation in autism.