Profiling of miRNAs in serum of children with attention-deficit hyperactivity disorder shows significant alterations

Abstract

Background: Attention-deficit/hyperactivity disorder (ADHD), a common psychiatric disorder, is identified by abnormal levels of impulsivity, inattention, and hyperactivity. MiRNAs play important roles in neural network development of the brain. Circulating miRNAs (cmiRNAs) are offered as promising noninvasive markers for psychiatric disorders. In this study, the expression level of neurologically relevant miRNAs was evaluated in serum samples of ADHD individuals.

Methods: RNA extraction was performed for 60 subjects with ADHD and 60 healthy controls, and the cDNAs were synthesized for all the miRNAs. The expression level of 84 cmiRNAs was then examined in 4 ADHD subjects and 4 controls. The altered expression of 10 cmiRNAs was further evaluated in validation cohort comprising 56 ADHD and 56 control samples by qPCR. The diagnostic power of the miRNAs was determined by use of Receiver-operating characteristic (ROC) analysis. The cmiRNAs target genes were predicted using DIANA mirPath software and gene ontology enrichment analysis was performed using Cytoscape CLUGO.

Results: Initially, 10 miRNAs showed differential expression in ADHD individuals. Further analysis confirmed four miRNAs (hsa-miR-101-3p, hsa-miR-130a-3p, hsa-miR-138-5p and hsa-miR-195-5p) upregulated and one miRNA (hsa-miR-106b-5p) downregulated. These miRNAs showed significant predictive values for discriminating ADHD individuals. Enrichment analysis highlighted the involvement of the deregulated cmiRNAs in many canonical neurobiological pathways and mechanisms.

Conclusions: Our report is the first comprehensive study on the expression profiling of miRNAs in serum of ADHD subjects. These findings suggest a set of cmiRNAs as potential noninvasive biomarkers for ADHD.

Keywords: Attention-deficit hyperactivity disorder; Circulating miRNAs; Gene expression; Profiling; Psychiatric disorders.