Document Type
Article
Publication Date
7-5-2021
Identifier
DOI: 10.3389/fpsyt.2021.668577; PMCID: PMC8288023
Abstract
Background: 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 (SERT) 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 SERT 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.
Design/methods: 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 SERT genotypes (LL/LS/SS) and prenatal stress level (high/low).
Results: 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 SERT genotypes, with high stress exposure, 20 significantly DE microRNAs were detected, five were stress-dependent. These microRNAs may be candidates for stress × SERT genotype interactions. This is remarkable as these changes were from mothers several years after stress-exposed pregnancies.
Conclusions: Our study provides evidence for epigenetic alterations in relation to a G × E model (prenatal maternal stress × SERT gene) in ASD.
Journal Title
Front Psychiatry
Volume
12
First Page
668577
Last Page
668577
Keywords
autism spectrum disorder; dopamine; epigenetics; gene x environment; miRNA; prenatal stress
Recommended Citation
Beversdorf DQ, Shah A, Jhin A, et al. microRNAs and Gene-Environment Interactions in Autism: Effects of Prenatal Maternal Stress and the SERT Gene on Maternal microRNA Expression. Front Psychiatry. 2021;12:668577. Published 2021 Jul 5. doi:10.3389/fpsyt.2021.668577
Comments
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Publisher's Link: https://www.frontiersin.org/articles/10.3389/fpsyt.2021.668577/full