Peripheral Blood Mononuclear Cell Oxytocin and Vasopressin Receptor Expression Positively Correlates with Social and Behavioral Function in Children with Autism

Irena Voinsky,Richard E Frye,Julie Svigals,Sirish C Bennuri,Shannon Rose,David Gurwitz

doi:10.1038/s41598-019-49617-9

Abstract

The peptide hormone oxytocin is an established regulator of social function in mammals, and dysregulated oxytocin signaling is implicated in autism spectrum disorder (ASD). Several clinical trials examining the effects of intranasal oxytocin for improving social and behavioral function in ASD have had mixed or inclusive outcomes. The heterogeneity in clinical trials outcomes may reflect large inter-individual expression variations of the oxytocin and/or vasopressin receptor genes OXTR and AVPR1A, respectively. To explore this hypothesis we examined the expression of both genes in peripheral blood mononuclear cells (PBMC) from ASD children, their non-ASD siblings, and age-matched neurotypical children aged 3 to 16 years of age as well as datamined published ASD datasets. Both genes were found to have large inter-individual variations. Higher OXTR and AVPR1A expression was associated with lower Aberrant Behavior Checklist (ABC) scores. OXTR expression was associated with less severe behavior and higher adaptive behavior on additional standardized measures. Combining the sum expression levels OXTR, AVPR1A, and IGF1 yielded the strongest correlation with ABC scores. We propose that future clinical trials in ASD children with oxytocin, oxytocin mimetics and additional tentative therapeutics should assess the prognostic value of their PBMC mRNA expression of OXTR, AVPR1A, and IGF1.

Highlights

The peptide hormone oxytocin is an established regulator of social function in mammals, and dysregulated oxytocin signaling is implicated in autism spectrum disorder (ASD)
We propose that future clinical trials in ASD children with oxytocin, oxytocin mimetics and additional tentative therapeutics should assess the prognostic value of their peripheral blood mononuclear cells (PBMC) mRNA expression of OXTR, AVPR1A, and IGF1
Our findings suggest that PBMC expression levels of OXTR, AVPR1A and IGF1 correlate with several standardized measures of behavior and development, including the Aberrant Behavior Checklist (ABC), Vineland Adaptive Behavior Scale (VABS), Social Responsiveness Scale (SRS), and Childhood Behavior Checklist (CBCL)

Summary

Introduction

The peptide hormone oxytocin is an established regulator of social function in mammals, and dysregulated oxytocin signaling is implicated in autism spectrum disorder (ASD). The heterogeneity in clinical trials outcomes may reflect large interindividual expression variations of the oxytocin and/or vasopressin receptor genes OXTR and AVPR1A, respectively. To explore this hypothesis we examined the expression of both genes in peripheral blood mononuclear cells (PBMC) from ASD children, their non-ASD siblings, and age-matched neurotypical children aged 3 to 16 years of age as well as datamined published ASD datasets. The closely similar peptide hormone arginine-vasopressin is implicated in social function via its V1AR receptor, encoded by AVPR1A24–27 Another peptide hormone studied as a tentative ASD therapeutic is insulin-like growth factor 1 (IGF-1), encoded in humans by IGF1. A single small study with recombinant human IGF-1 reported favorable response in ASD children[28] and another study (NCT01970345) is ongoing

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