The Prospective Role of Epigenetics in Attention-deficit/Hyperactivity Disorderdeficit/Hyperactivity Disorder

Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders in children and adolescents. ADHD's nosology is largely based on clinical phenomenology that includes such symptoms as inattention, hyperactivity and impulsivity. However, a reliable ADHD biomarker has still not been determined either for differential diagnosis or for monitoring treatment effects. MicroRNAs (miRNAs) are small non-coding RNA molecules that function in the process of RNA silencing and the post-transcriptional regulation of gene expression. MiRNAs are found in abundance throughout the nervous system and play a vital role in the transcriptional networks with regards to human brain development. Currently, miRNAs' involvement in the pathogenesis of ADHD continues to be unclear. Therefore, this study aims to investigate the prospective role of miRNAs in ADHD and to determine whether miRNA levels in peripheral blood can serve as a biomarker and a diagnosis panel for ADHD.

In the preliminary study, blood samples were collected from five patients with ADHD and five healthy control subjects. The use of Next Generation Sequencing (NGS) techniques has identified 23 miRNAs as potential biomarkers for ADHD. During this three-year proposal, we intend to recruit 100 drug-naïve patients with ADHD and 100 age- and gender-matched control subjects (Training Set). Blood will be obtained through direct puncture of the vein from each participant to analyze the miRNAs by using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The behavior and neuropsychology of each participant will be assessed. This research will construct a miRNAs diagnosis panel using the Support Vector Machine (SVM) classification model to discriminate ADHD from non-ADHD. The validity of the miRNA diagnosis panel will then be re-examined using an independent validation sample composed of 50 patients with ADHD and 50 control subjects (Testing Set). All of the 150 patients with ADHD will receive treatment in a traditional clinical practice and then will be followed up with for 12 months. At the twelfth month, the same procedures as those performed at the baseline will be replicated to examine the influence of ADHD medications on miRNAs, as well as determine whether miRNAs can serve as a biomarker to portray the condition of ADHD under treatment. MiRNA target gene prediction and functional annotation analysis will also be performed.

This study will develop a potential diagnostic panel for ADHD through the use of combinations of multiple miRNA expressions. We will provide proof of the relationships of miRNAs profiles and ADHD manifestations in clinical samples and further explain the molecular pathogenesis of ADHD. Such information may become an important reference for future research and clinical treatments for patients with ADHD.