Blood-Bourne MicroRNA Biomarker Evaluation in Attention-Deficit/Hyperactivity Disorder of Han Chinese Individuals: An Exploratory Study

Abstract

Background: Attention-deficit/hyperactivity disorder (ADHD) is a highly genetic neurodevelopmental disorder, and its dysregulation of gene expression involves microRNAs (miRNAs). The purpose of this study was to identify potential miRNAs biomarkers and then use these biomarkers to establish a diagnostic panel for ADHD.Design and methods: RNA samples from white blood cells (WBCs) of five ADHD patients and five healthy controls were combined to create one pooled patient library and one control library. We identified 20 candidate miRNAs with the next-generation sequencing (NGS) technique (Illumina). Blood samples were then collected from a Training Set (68 patients and 54 controls) and a Testing Set (20 patients and 20 controls) to identify the expression profiles of these miRNAs with real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). We used receiver operating characteristic (ROC) curves and the area under the curve (AUC) to evaluate both the specificity and sensitivity of the probability score yielded by the support vector machine (SVM) model.Results: We identified 13 miRNAs as potential ADHD biomarkers. The ΔCt values of these miRNAs in the Training Set were integrated to create a biomarker model using the SVM algorithm, which demonstrated good validity in differentiating ADHD patients from control subjects (sensitivity: 86.8%, specificity: 88.9%, AUC: 0.94, p < 0.001). The results of the blind testing showed that 85% of the subjects in the Testing Set were correctly classified using the SVM model alignment (AUC: 0.91, p < 0.001). The discriminative validity is not influenced by patients' age or gender, indicating both the robustness and the reliability of the SVM classification model.Conclusion: As measured in peripheral blood, miRNA-based biomarkers can aid in the differentiation of ADHD in clinical settings. Additional studies are needed in the future to clarify the ADHD-associated gene functions and biological mechanisms modulated by miRNAs.

MiRNA profiles in blood plasma from mother-child duos in human biobanks and the implication of sample quality: Circulating miRNAs as potential early markers of child health

“…[45] hsa-miR-151a-5p 4.07 ±1.47 2.01 ±0.76 Part of ADHD-prediction model in WBCs. [43] hsa-miR-18a-5p 2.63 ±0.53 2.86 ±0.89 Decreased in WB. [37] hsa-miR-191-5p 3.03 ±0.91 2.81 ±1.43 Increased in PBMCs.…”

“…[40][41][42] hsa-let-7g-5p 3.23 ±1. 24 2.87 ±1.32 Part of ADHD-prediction model in WBCs [43] hsa-miR-101-3p 2.13 ±0. 30 3.50 ±0.87 Part of ADHD-prediction model in WBCs, and increased in serum.…”

“…30 3.50 ±0.87 Part of ADHD-prediction model in WBCs, and increased in serum. [43,44] hsa-miR-107 2.27 ±0. 39 1.87 ±0.44 Decreased in WB.…”

“…[38] hsa-miR-30e-5p 3.97 ±1.58 1.38 ±0.24 Part of ADHD-prediction model in WBCs, and increased in WBCs. [39,43] Mean NRQ and standard error (SE) of the mean. WB: Whole blood; WBCs: White blood cells; PBMCs: Peripheral blood mononuclear cells.…”

Epigenetics and Attention-Deficit/Hyperactivity Disorder: New Perspectives?

“…Pathological processes in the central nervous system can be reflected in peripheral tissues (17). Many circulating miRNAs (18a-5p, 22-3p, 24-3p, 106b-5p, 107, 155a-5p, let-7d) have been associated with ADHD, including via next-generation sequencing (27)(28)(29).…”