Neurochemical Correlates of Executive Function in Children with Attention-Deficit/Hyperactivity Disorder.

Objectives: Attention-Deficit/Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder with no known biomarkers. The objectives of this study were 1) to investigate spectroscopic biomarkers in the right prefrontal cortex (R-PFC) and left striatum; 2) to evaluate Executive Function (EF) performance; and, 3) to examine the clinical relevance of glutamate in EF tasks. Methods: A total of 21 children with ADHD (M = 10.41 years, SD = 1.41) and 15 controls without ADHD (M = 9.90 years, SD = 1.54 years) were enrolled. Short echo proton magnetic resonance spectroscopy (1H-MRS; TE = 30ms) was used to study the changes in the R-PFC and left striatum. Both groups completed an EF assessment battery, including working memory, inhibition, cognitive flexibility and verbal fluency tasks. Results: In the R-PFC, independent t-tests found decreased concentration of glutamate (p = 0.009), NAA (p = 0.029) and choline (p = 0.016) in ADHD participants compared to controls. No significant differences were seen in the left striatum. Multivariate analysis of variance did not indicate overall EF challenges in the ADHD sample (p < .05). Positive correlations with glutamate concentration and EF performance in the control group were observed, however, no such correlations were reported in the ADHD group. Conclusions: The results indicated a subgroup of children with ADHD who presented with hypo-glutamatergic signalling in the R-PFC. Additionally, findings suggested a decoupling effect of glutamate in EF related tasks in children with ADHD compared to controls. Thus, glutamate concentration may be a possible ADHD biomarker and novel treatments target.