Abstract
Intranasal administration of the neuropeptide oxytocin (IN-OT) is increasingly explored as a potential treatment for targeting the core symptoms of autism spectrum disorder (ASD). To date, however, the impact of multiple-dose IN-OT treatment on human neural circuitry is largely unknown, and also the possibility that long-term IN-OT use may induce long-lasting neural adaptations remains unexplored. Using a double-blind, randomized, placebo-controlled, between-subject design (including 38 adult men with ASD), this treatment-mechanism study showed that 4 weeks of daily oxytocin administration (24 IU/day) significantly altered intrinsic (resting-state fMRI) functional connectivity of the amygdala to core regions of the “social brain” (particularly orbitofrontal cortex and superior temporal sulcus) up to 4 weeks and 1 year post treatment. The neural adaptations in functional coupling of the amygdala to the orbitofrontal cortex were associated with reduced feelings of avoidance toward others and—at the trend level—reduced repetitive behaviors. These observations contribute to a deeper mechanistic understanding of the neural substrates that underlie behavioral effects of multiple-dose IN-OT treatment, and provide initial insights into the long-lasting neural consequences of chronic IN-OT use on amygdala circuitry. Future studies are however warranted to further elucidate the long-term impact of IN-OT treatment on human neural circuitry and its behavioral consequences.
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Acknowledgements
We would like to thank Emmely Berra for her help in data collections. We would also like to thank all the participants of the study and our colleagues of the Leuven Autism Research Consortium (LAuRes).
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KA, JS, and NW designed the study. SB and CD acquired the data. KA analyzed the data and wrote the paper. SB, JP, JS, and NW provided intellectual contribution to the data analyses and revised the paper. All authors read and approved the final paper.
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Alaerts, K., Bernaerts, S., Prinsen, J. et al. Oxytocin induces long-lasting adaptations within amygdala circuitry in autism: a treatment-mechanism study with randomized placebo-controlled design. Neuropsychopharmacol. 45, 1141–1149 (2020). https://doi.org/10.1038/s41386-020-0653-8
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DOI: https://doi.org/10.1038/s41386-020-0653-8
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