Gray matter volume and microRNA levels in patients with attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder often characterized by gray matter (GM) volume reductions. MicroRNAs, which participate in regulating gene expression, potentially influence neurodevelopment. This study aimed to explore whether differential GM volume is associated with differential miRNA levels in ADHD patients. We recruited a total of 30 drug-naive patients with ADHD (mean age 10.6 years) and 25 healthy controls (mean age 10.6 years) that underwent a single session of 3.0-T whole brain structural MRI scanning. RNA samples from the participants' white blood cells were collected to identify the Delta Ct values of three miRNAs (miR-30e-5p, miR-126-5p, and miR-140-3p) using the real-time quantitative reverse transcription polymerase chain reaction. In comparison to the control group, ADHD patients demonstrated a significantly lower GM volume in the cingulate gyrus, left middle temporal gyrus, right middle occipital gyrus, left fusiform gyrus, and significantly higher Delta Ct values of miR-30e-5p, miR-126-5p, and miR-140-3p. In the ADHD group, the GM volume of cingulate gyrus and left fusiform gyrus was negatively correlated with the Delta Ct values of miR-30e-5p, miR-140-3p. The GM volume of left fusiform gyrus was negatively correlated to ADHD behavioral symptoms. Using structural equation modeling (SEM), we observed that the effect of miR-140-3p on hyperactivity/impulsivity symptoms was mediated by left fusiform gyrus. Our findings support that GM volume reduction and miRNA increases may be biomarkers for ADHD in children and adolescents. Expression levels of miRNAs may affect the development of brain structures and further participate in the pathophysiology of ADHD.