Researchers looked at the oxytocin receptor (OXTR) in brain tissue from people with autism and found higher levels of OXTR messenger RNA in certain brain areas, but this doesn't tell us anything useful for everyday health hacks or performance improvement.

The 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. We used adjacent sections from the same specimens from our previous study and performed duplex fluorescent <i>in situ</i> hybridization to visualize and quantify <i>OXTR</i> mRNA in the ventral pallidum (VP) and in the cholinergic magnocellular neurons of the nucleus basalis of Meynert (NBM), visualized with choline acetyltransferase (<i>ChAT</i>). We genotyped the brain samples using a SNP microarray on extracted DNA. We then used regression models to test associations between OXTR binding density, <i>OXTR</i> mRNA levels, and relevant <i>OXTR</i> SNPs. Additionally, we tested for correlation between age and <i>OXTR</i> mRNA. ASD specimens showed significantly greater <i>OXTR</i> mRNA than unaffected donors in both the VP and the NBM. Furthermore, this is the first demonstration of <i>OXTR</i>expression in the cholinergic neurons of the human basal forebrain; 73% of <i>OXTR</i> signal in the images of the <i>ChAT+</i> neurons were colocalized with the cholinergic neurons. OXTR binding levels from our previous study were positively associated with <i>OXTR</i> mRNA in the NBM of control specimens but not in ASD specimens, implying potential dysregulation at the level of protein translation or mRNA trafficking in the NBM in ASD. OXTR binding levels were not associated with <i>OXTR</i>mRNA in the VP of either group. We genotyped all specimens for three common SNPs in the <i>OXTR</i> 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. Taken together, our results contribute to a more nuanced picture triangulating variation in <i>OXTR</i> gene sequence, gene expression, protein levels, and human behavior. Clinical trial number: not applicable.