Functional implications of oxytocin receptor expression patterns in the human brain across the lifespan

Abstract

The neuropeptide oxytocin has attracted considerable interest for its role in social behavior and its potential for the treatment of psychiatric illnesses characterised by social dysfunction. However, the distribution of oxytocin receptors in the human brain, and the functional significance of expression patterns, are poorly understood. Our aim was to characterise gene expression patterns of the oxytocin receptor (OXTR) gene across the lifespan and the association of these expression patterns with cognitive states in adulthood, to better understand the functional relevance of the oxytocin signalling system. mRNA expression values were identified from post-mortem brain samples across the lifespan using the Brainspan and Allen Human Brain Atlas databases. Voxel-by-voxel gene expression values were calculated from the adult post-mortem samples, which provided high spatial resolution. Voxel-by-voxel OXTR maps were correlated against 20,736 generated maps of protein coding genes, to identify the strongest associations of gene expression patterns. Mental state correlates of oxytocin receptor expression were identified by performing a large-scale meta-analysis of 14,371 fMRI studies, using the NeuroSynth platform. Whole-brain oxytocin receptor expression was enriched in late childhood. In adulthood, OXTR was enriched in subcortical and olfactory regions and highly co-expressed with several dopaminergic and muscarinic acetylcholine genes. OXTR expression patterns were most strongly correlated with the brain expression patterns of genes associated with metabolic regulation. The OXTR expression map corresponded with the brain activity patterns associated with social, anticipatory, appetitive, and aversive cognitive states. OXTR enrichment in early childhood compared to the rest of the lifespan suggests that oxytocin signalling plays a particularly important role in this critical developmental period. While OXTR expression patterns in adulthood were associated with social cognitive states, which is consistent with prior work, our results point to a more complex role in human behaviour. The data also suggests that oxytocin signalling is critically involved in metabolic regulation. Altogether, our results illustrate the sophisticated nature of oxytocin signalling in the human brain, which may help guide future therapeutic interventions with intranasal oxytocin

Date
Location
SCNP annual meeting, Gothenburg, Sweden