RESUMO
BACKGROUND: Children with attention-deficit/hyperactivity disorder (ADHD) often exhibit behaviour challenges and deficits in executive functions (EF). Psychostimulant medications [e.g., methylphenidate (MPH)] are commonly prescribed for children with ADHD and are considered effective in 70% of the cases. Furthermore, only a handful of studies have investigated the long-term impact of MPH medication on EF and behaviour. AIM: To evaluate behaviour and EF challenges in children with ADHD who were involved in an MPH treatment trial across three-time points. METHODS: Thirty-seven children with ADHD completed a stimulant medication trial to study the short- and long-term impact of medication. Children with ADHD completed three neuropsychological assessments [Continuous Performance Test (CPT)-II, Digit Span Backwards and Spatial Span Backwards]. Parents of children with ADHD completed behaviour rating scales [Behaviour Rating Inventory of Executive Functioning (BRIEF) and Behaviour Assessment System for Children-Second Edition (BASC-2)]. Participants were evaluated at: (1) Baseline (no medication); and (2) Best-dose (BD; following four-week MPH treatment). Additionally, 18 participants returned for a long-term naturalistic follow up (FU; up to two years following BD). RESULTS: Repeated measure analyses of variance found significant effects of time on two subscales of BRIEF and four subscales of BASC-2. Neuropsychological assessments showed some improvement, but not on all tasks following the medication trial. These improvements did not sustain at FU, with increases in EF and behaviour challenges, and a decline in performance on the CPT-II task being observed. CONCLUSION: Parents of children with ADHD reported improvements in EF and behaviours during the MPH trial but were not sustained at FU. Combining screening tools and neuropsychological assessments may be useful for monitoring medication responses.
RESUMO
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.
OBJECTIFS: Le trouble de déficit de l'attention avec hyperactivité (TDAH) est un trouble neurodéveloppemental prévalent sans biomarqueurs connus. Les objectifs de la présente étude étaient 1) de rechercher les biomarqueurs spectroscopiques du cortex préfrontal droit (CPF-D) et du striatum gauche; 2) d'évaluer le rendement de la fonction exécutive (FE); et 3) d'examiner la pertinence clinique du glutamate dans les tâches de la FE. MÉTHODES: Au total, 21 enfants souffrant du TDAH (M = 10,41 ans, ET = 1,41) et 15 témoins sans TDAH (M = 9,90 ans, ET = 1,54 an) ont été inscrits. La spectroscopie par résonance magnétique protonique à bref temps d'écho (1H-SRM; TE = 30 ms) a servi à étudier les changements dans le CPF-D et le striatum gauche. Les deux groupes ont passé une batterie de tests d'évaluation de la FE, dont les tâches de la mémoire de travail, l'inhibition, la flexibilité cognitive et la fluidité verbale. RÉSULTATS: Dans le CPF-D, les t-tests indépendants ont constaté une concentration réduite de glutamate (p = 0,009), de NAA (p = 0,029) et de choline (p = 0,016) chez les participants du TDAH comparés aux témoins. Aucune différence significative n'a été observée dans le striatum gauche. Des analyses multivariées de la variance n'ont pas indiqué de problèmes généraux pour la FE dans l'échantillon TDAH (p < 0,05). Des corrélations positives avec la concentration de glutamate et le rendement de la FE dans le groupe témoin ont été observées, toutefois, ces corrélations n'ont pas été observées dans le groupe du TDAH. CONCLUSIONS: Les résultats indiquaient un sous-groupe d'enfants souffrant du TDAH qui présentait un signal hypo-glutamatergique dans le CPF-D. En outre, les résultats suggéraient un effet de découplage du glutamate dans les tâches liées à la FE chez les enfants souffrant du TDAH comparés aux témoins. Ainsi, la concentration de glutamate peut être un biomarqueur du TDAH et une nouvelle cible de traitement.
