AUTHOR=Beversdorf David Q. , Shah Ayten , Jhin Allison , Noel-MacDonnell Janelle , Hecht Patrick , Ferguson Bradley J. , Bruce Danielle , Tilley Michael , Talebizadeh Zohreh 

TITLE=microRNAs and Gene–Environment Interactions in Autism: Effects of Prenatal Maternal Stress and the SERT Gene on Maternal microRNA Expression

JOURNAL=Frontiers in Psychiatry

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2021.668577

DOI=10.3389/fpsyt.2021.668577

ISSN=1664-0640

ABSTRACT=<p><bold>Background:</bold> Genetics and environment both are critical in autism spectrum disorder (ASD), but their interaction (G × E) is less understood. Numerous studies have shown higher incidence of stress exposures during pregnancies with children later diagnosed with ASD. However, many stress-exposed mothers have unaffected children. The serotonin transporter (<italic>SERT</italic>) gene affects stress reactivity. Two independent samples have shown that the association between maternal stress exposure and ASD is greatest with maternal presence of the <italic>SERT</italic> short (S)-allele (deletion in the promoter region). MicroRNAs play a regulatory role in the serotonergic pathway and in prenatal stress and are therefore potential mechanistic targets in this setting.</p><p><bold>Design/methods:</bold> We profiled microRNA expression in blood from mothers of children with ASD, with known stress exposure during pregnancy. Samples were divided into groups based on <italic>SERT</italic> genotypes (LL/LS/SS) and prenatal stress level (high/low).</p><p><bold>Results:</bold> Two thousand five hundred mature microRNAs were examined. The ANOVA analysis showed differential expression (DE) of 119 microRNAs; 90 were DE in high- vs. low-stress groups (stress-dependent). Two (miR-1224-5p, miR-331-3p) were recently reported by our group to exhibit stress-dependent expression in rodent brain samples from embryos exposed to prenatal stress. Another, miR-145-5p, is associated with maternal stress. Across <italic>SERT</italic> genotypes, with high stress exposure, 20 significantly DE microRNAs were detected, five were stress-dependent. These microRNAs may be candidates for stress × <italic>SERT</italic> genotype interactions. This is remarkable as these changes were from mothers several years after stress-exposed pregnancies.</p><p><bold>Conclusions:</bold> Our study provides evidence for epigenetic alterations in relation to a G × E model (prenatal maternal stress × <italic>SERT</italic> gene) in ASD.</p>