ArticleJournal of neurodevelopmental disorders2026
Oxytocin receptor gene expression in the basal forebrain in autism: association with receptor binding levels and single nucleotide polymorphisms.
Article in Journal of neurodevelopmental disorders, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundThe brain’s oxytocin system has been implicated in the neurobiology of autism (ASD), given the role of oxytocin in modulating social function in humans and animals more broadly. Previous work from members of our group reported dysregulation in oxytocin receptor (OXTR) binding in postmortem tissue from the basal forebrain in donors with autism compared to unaffected control donors. This study follows up on those findings by investigating the potential genetic and gene expression changes that could be driving those differences.
methodsWe used adjacent sections from the same specimens from our previous study and performed duplex fluorescence in situ hybridization to visualize and quantify OXTR mRNA in the ventral pallidum (VP) and in the cholinergic magnocellular neurons of the nucleus basalis of Meynert (NBM), visualized with choline acetyltransferase (ChAT). We genotyped the brain samples using a SNP microarray on extracted DNA. We then used regression models to test associations between OXTR binding density, OXTR mRNA levels, and relevant OXTR SNPs. Additionally, we tested for correlations between age and OXTR mRNA.
resultsASD specimens showed significantly greater OXTR mRNA than unaffected donors in both the VP and the NBM. Furthermore, this is the first demonstration of OXTR expression in the cholinergic neurons of the human basal forebrain; 73% of OXTR signal in the images of the ChAT+ neurons were colocalized with the cholinergic neurons. OXTR binding levels from our previous study were positively associated with OXTR mRNA in the NBM but only in the ChAT+ neurons there. OXTR binding levels were not associated with OXTR mRNA in the VP. We genotyped all specimens for three common SNPs in the OXTR gene that have been associated with ASD in the literature, but none significantly predicted levels of OXTR binding or gene expression in the NBM or VP. OXTR mRNA levels were strongly positively correlated with donor age across regions, which was driven by ASD specimens.
conclusionsTaken together, our results contribute to a more nuanced picture triangulating variation in OXTR gene sequence, gene expression, protein levels, and human behavior.
trial registrationClinical trial number: not applicable.
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