Oxytocin gene networks in the human brain: A gene expression and large-scale fMRI meta-analysis study

Abstract

AbstractOxytocin is a neuropeptide involved in animal and human reproductive and social behavior, with implications for a range of psychiatric disorders. However, the therapeutic potential of oxytocin in mental health care suggested by animal research has not been successfully translated into clinical practice. This may be partly due to a poor understanding of the expression and distribution of the oxytocin signaling pathway in the human brain, and its complex interactions with other biological systems. Among the genes involved in the oxytocin signaling pathway, three genes have been frequently implicated in human social behavior: OXT (structural gene for oxytocin), OXTR (oxytocin receptor), and CD38 (central oxytocin secretion). We characterized the distribution of OXT, OXTR, and CD38 mRNA across the brain, identified putative gene pathway interactions by comparing gene expression patterns across 20737 genes, and assessed associations between gene expression patterns and mental states via large-scale fMRI metaanalysis. In line with the animal literature, expression of the three selected oxytocin pathway genes was increased in central, temporal, and olfactory regions. Across the brain, there was high co-expression with several dopaminergic and muscarinic acetylcholine genes, reflecting an anatomical basis for critical gene pathway interactions. Finally, fMRI meta-analysis revealed that the oxytocin pathway gene maps correspond with motivation and emotion processing.