Differential microRNA expression in adolescent anxiety proneness

Abstract

Biological mechanisms underlying anxiety proneness (AP), the tendency to react fearfully to stressors due to the belief that experiencing anxiety has harmful consequences, remain unclear. Epigenetic mechanisms, such as microRNAs (small, non-coding RNAs 19-20 nucleotides long), may be contributory. This study investigated AP-associated differences in microRNA expression among South African adolescents with variable exposure to childhood trauma (CT). AP was assessed using a composite score reflecting trait anxiety and anxiety sensitivity, while CT exposure was assessed with the Childhood Trauma Questionnaire. High-quality total RNA (n = 88) extracted from whole blood underwent microRNA-sequencing. Differential microRNA expression analysis was conducted with DESeq2 in R, messenger RNA target prediction analysis was performed using TargetScan and DIANA-microT, and the DIANA mirPATH tool was used for KEGG pathway analysis. The majority of participants were female (75.86%) with an average age of 15 (±1.19) years. MicroRNA expression analysis identified upregulation of hsa-miR-28-5p and downregulation of hsa-miR-502-3p and hsa-miR-500a-3p in high-AP individuals, irrespective of CT. Four KEGG pathways, each with ≥10% of their constituent genes predicted to be targets of the differentially expressed microRNAs, were identified and were enriched for genes involved in calcineurin and glutamate signalling. These findings suggest that epigenetically mediated effects on neuronal function contribute to the molecular aetiology of AP.

Keywords: anxiety proneness; childhood trauma; epigenetics; glutamate; microRNA.