Oxytocin receptor expression patterns in the human brain across development

Background: Oxytocin plays a vital role in social behavior and homeostatic processes, with animal models indicating that oxytocin receptor (OXTR) expression patterns in the brain influence behavior and physiology. However, the developmental trajectory of OXTR gene expression is unclear, which is considerable knowledge gap as many psychiatric illnesses emerge early in life and genes tend to be differentially regulated across development. Methods: We calculated spatiotemporal expression patterns for 16660 genes in the human brain using transcriptome data from 57 donors across the lifespan. Next, we explored the evolutionary origin of these patterns using a comparative gene expression dataset from 38 macaque donors. Finally, we determined the functional significance of OXTR spatiotemporal co-expression patterns via the annotation of genetic associations with psychiatric and body composition phenotypes.Results: OXTR expression in the brain accelerated before birth with a peak in early childhood and OXTR expression was highly correlated with dopamine receptor D2 expression across development. These gene expression patterns were not observed in a comparative macaque sample, suggesting they might be evolutionarily new features. In addition, a network of genes strongly spatiotemporally coupled with OXTR was enriched in schizophrenia, cognitive, and body composition phenotypes, with elements of this gene network having undergone positive selection in humans but not macaques.Conclusions: These results demonstrate that oxytocin signaling plays an important role in a diverse set of psychological and physiological processes across the lifespan. Identifying a critical window of OXTR expression in the brain, together with associated genes, may help illuminate our understanding of disease etiology.