Abstract
Oxytocin is a neuropeptide involved in animal and human reproductive and social behavior. Three oxytocin signaling genes have been frequently implicated in human social behavior: OXT (structural gene for oxytocin), OXTR (oxytocin receptor), and CD38 (oxytocin secretion). Here, we characterized the distribution of OXT, OXTR, and CD38 mRNA across the human brain by creating voxel-by-voxel volumetric expression maps, and identified putative gene pathway interactions by comparing gene expression patterns across 20,737 genes. Expression of the three selected oxytocin pathway genes was enriched in subcortical and olfactory regions and there was high co-expression with several dopaminergic and muscarinic acetylcholine genes, reflecting an anatomical basis for critical gene pathway interactions. fMRI meta-analysis revealed that the oxytocin pathway gene maps correspond with the processing of anticipatory, appetitive, and aversive cognitive states. The oxytocin signaling system may interact with dopaminergic and muscarinic acetylcholine signaling to modulate cognitive state processes involved in complex human behaviors.
Highlights
The results from a large-scale fMRI metaanalysis suggest that oxytocin pathway gene expression maps correspond with the processing of anticipatory, appetitive, and aversive cognitive states. These results indicate that the oxytocin signaling system may operate synergistically with the dopaminergic and muscarinic acetylcholine signaling systems to exert its complex effects on cognition
Decoding cognitive states meta-analytically from voxel-byvoxel mRNA maps (Fig. 6) via quantitative reverse inference revealed that oxytocin receptor (OXTR), CD38, and oxytocin-neurophysin I (OXT) mRNA expression maps were most highly correlated with functional imaging maps that can be broadly categorized as anticipatory, appetitive, and aversive (Fig. 7a, Supplementary Table 2)
All correlation coefficient p-values for the relationship between each cognitive state term and oxytocin pathway genes (OXTR, CD38, and OXT) are presented in Supplementary Table 2
Summary
Oxytocin gene expression patterns in the brain. The full dataset of protein coding genes (n = 20,737) from six donor brains were collected from the Allen Human Brain Atlas (http://human.brainmap.org/). The Genotype-Tissue Expression (GTEx) project database[30] was used for independent sample validation. This dataset provides gene expression data from fewer brain regions (i.e., 10) compared to the Allen dataset, the data is derived from a larger dataset of donors (mean sample size for mRNA expression across brain regions = 131.7, range = 88–173). Median gene expression profiles from 10 distinct brain regions were extracted for the above-specified 20 genes of interest from the GTEx database and median values were calculated for these same 10
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