Blood miRNA levels associated with ADHD traits in children across six European birth cohorts

Abstract

Background Attention-deficit/hyperactivity disorder (ADHD) is a prevalent and highly heritable neurodevelopmental disorder of major societal concern. Diagnosis can be challenging and there are large knowledge gaps regarding its etiology, though studies suggest an interplay of genetic and environmental factors involving epigenetic mechanisms. MicroRNAs (miRNAs) show promise as biomarkers of human pathology and novel therapies, and here we aimed to identify blood miRNAs associated with traits of ADHD as possible biomarker candidates and further explore their biological relevance. Methods Our study population consisted of 1126 children (aged 5–12 years, 46% female) from the Human Early Life Exposome study, a study spanning six ongoing population-based European birth cohorts. Expression profiles of miRNAs in whole blood samples were quantified by microarray and tested for association with ADHD-related measures of behavior and neuropsychological functions from questionnaires (Conner’s Rating Scale and Child Behavior Checklist) and computer-based tests (the N-back task and Attention Network Test). Results We identified 29 miRNAs significantly associated (false discovery rate < .05) with the Conner’s questionnaire-rated trait hyperactivity, 15 of which have been linked to ADHD in previous studies. Investigation into their biological relevance revealed involvement in several pathways related to neurodevelopment and function, as well as being linked with other neurodevelopmental or psychiatric disorders known to overlap with ADHD both in symptomology, genetic risk, and co-occurrence, such as autism spectrum disorder or schizophrenia. An additional three miRNAs were significantly associated with Conner’s-rated inattention. No associations were found with questionnaire-rated total ADHD index or with computer-based tests. Conclusions The large overlap of our hyperactivity-associated miRNAs with previous studies on ADHD is intriguing and warrant further investigation. Though this study should be considered explorative and preliminary, these findings contribute towards identifying a set of miRNAs for use as blood-based biomarkers to aid in earlier and easier ADHD diagnosis.

Advances in the etiology and neuroimaging of children with attention deficit hyperactivity disorder

“…Srivastav et al ( 69 ) observed that peripheral microRNA concentrations were different in both animal models and children with ADHD. In 2023, Dypås et al discovered 32 microRNAs that were strongly linked to features related to ADHD, including hyperactivity (29) and inattention (3) ( 70 ).…”

Expression Patterns of miRNAs in Egyptian Children with ADHD: Clinical Study with Correlation Analysis

“…The prevalence of attention deficit hyperactivity (ADHD) in worldwide population is estimated to be 5.9% among youths and 2.5% among adults (Faraone et al 2021 ). Diagnosis of ADHD is challenging due to missing gaps related to knowledge of its etiology (Dypås et al 2024 ). Individuals with ADHD were reported to have differences in their brain processes, which produce changes in personal, social, academic, and occupational functioning (American Psychiatric Association 2022 ).…”