Autism-risk gene mutations convergently disrupt sexually dimorphic oxytocin circuits to lower social engagement

Patwardhan, A.; Moslemian, A.; Tse, E. E.; Grinevich, V.; Choe, K. Y.

doi:10.64898/2026.08.27.747579

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bioRxiv · 10.64898/2026.08.27.747579

Autism-risk gene mutations convergently disrupt sexually dimorphic oxytocin circuits to lower social engagement

Patwardhan, A.·Moslemian, A.·Tse, E. E.·Grinevich, V.·Choe, K. Y.

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Abstract

Autism arises from diverse genetic risk factors, yet how they converge to produce core symptoms and contribute to its sex bias remains unestablished. Oxytocin increases sociability in multiple murine autism models, presenting an opportunity to identify a potentially shared mechanistic basis across etiologies. Here we show that spontaneous social investigation triggers overlapping patterns of aberrant functional connectivity across social and sensory brain regions in two knockout (KO) mouse models, which are rescued by oxytocin. We also report that, during social investigation, wildtype mice exhibit sexually dimorphic oxytocin release and neuronal activity dynamics in the nucleus accumbens and the amygdala. These patterns are disrupted in both KO models, but can be restored by sex- and circuit-specific stimulation of endogenous oxytocin release, accompanied by enhanced social engagement. These findings identify impaired oxytocin recruitment of sexually dimorphic social circuits as a convergent consequence of autism-risk gene mutations that may underlie low sociability.

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Patwardhan, A., Moslemian, A., Tse, E. E., Grinevich, V., Choe, K. Y.. 2026-09-01. Autism-risk gene mutations convergently disrupt sexually dimorphic oxytocin circuits to lower social engagement. https://doi.org/10.64898/2026.08.27.747579

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