# μ Opioid Modulation of Sensorimotor Functional Connectivity in Autism: Insights From a Pharmacological Neuroimaging Investigation Using Tianeptine

## TL;DR

This study explores how the opioid system affects brain connectivity in autism, finding that a drug called tianeptine increases sensorimotor network connectivity in autistic individuals.

## Contribution

The study provides first evidence linking μ opioid modulation to sensorimotor functional connectivity differences in autism.

## Key findings

- Tianeptine increased sensorimotor network connectivity in autistic individuals.
- Frontoparietal network connectivity was not significantly affected by tianeptine.
- The findings suggest μ opioid signaling may contribute to sensorimotor differences in autism.

## Abstract

Reproducible patterns of atypical functional connectivity (FC) of sensorimotor and higher-order networks have previously been identified in the autistic brain. However, the neurosignaling pathways underpinning these differences remain unclear. The μ opioid system is involved in sensory processing as well as social and reward behaviors and has been implicated in autism, suggesting a potential role in shaping the autistic brain. Therefore, 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, randomized, crossover study design to compare the effects of a single dose of the μ opioid receptor agonist tianeptine in autistic (n = 20) and nonautistic (n = 21) males on FC of sensorimotor and frontoparietal networks.

We found that tianeptine increased FC of a sensorimotor network previously characterized by atypically low FC in autism. The connectivity of the frontoparietal network was not significantly shifted.

Our findings suggest that μ opioid neurosignaling may contribute to functional brain differences in the sensorimotor network in autism. Given that sensorimotor system alterations are thought to be central 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.

Reproducible patterns of atypical brain connectivity have been identified in autism. However, the underlying molecular mechanisms remain unclear. In this study, we measured the effects of the μ opioid receptor agonist tianeptine on brain connectivity in autistic and nonautistic men. We found that, in the former, tianeptine increased connectivity of sensorimotor regions previously characterized by atypically low connectivity. This suggests a role for μ opioid signaling in sensorimotor differences in autism and possibly downstream adaptive behaviors and mental health.

Reproducible patterns of atypical brain connectivity have been identified in autism. However, the underlying molecular mechanisms remain unclear. In this study, we measured the effects of the μ opioid receptor agonist tianeptine on brain connectivity in autistic and nonautistic men. We found that, in the former, tianeptine increased connectivity of sensorimotor regions previously characterized by atypically low connectivity. This suggests a role for μ opioid signaling in sensorimotor differences in autism and possibly downstream adaptive behaviors and mental health.