TY - JOUR
T1 - Peripheral Blood Mononuclear Cell Oxytocin and Vasopressin Receptor Expression Positively Correlates with Social and Behavioral Function in Children with Autism
AU - Voinsky, Irena
AU - Bennuri, Sirish C.
AU - Svigals, Julie
AU - Frye, Richard E.
AU - Rose, Shannon
AU - Gurwitz, David
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85072279252&partnerID=8YFLogxK
U2 - 10.1038/s41598-019-49617-9
DO - 10.1038/s41598-019-49617-9
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C2 - 31530830
AN - SCOPUS:85072279252
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 13443
ER -