Stimulant medication use and apparent cortical thickness development in attention-deficit/hyperactivity disorder: a prospective longitudinal study
Authors: van der Pal Zarah , Walhovd Kristine B , Amlien Inge K , Guichelaar Carlijn Jamila , Kaiser Antonia , Bottelier Marco A , Geurts Hilde M , Reneman Liesbeth , Schrantee Anouk 
Published: August 2023

AbstractBackgroundStimulant medication is commonly prescribed as treatment for attention-deficit/hyperactivity disorder (ADHD). While we previously found that short-term stimulant-treatment influences apparent cortical thickness development in an age-dependent manner, it remains unknown whether these effects persist throughout development into adulthood.PurposeInvestigate the long-term age-dependent effects of stimulant medication on apparent cortical thickness development in adolescents and adults previously diagnosed with ADHD.MethodsThis prospective study included the baseline and 4-year follow-up assessment of the “effects of Psychotropic drugs On the Developing brain-MPH” (“ePOD-MPH”) project, conducted between June-1-2011 and December-28-2019. The analyses were pre-registered (https://doi.org/10.17605/OSF.IO/32BHF). T1-weighted MR scans were obtained from male adolescents and adults, and cortical thickness was estimated for predefined regions of interest (ROIs) using Freesurfer. We determined medication use and assessed symptoms of ADHD, anxiety, and depression at both time points. Linear mixed models were constructed to assess main effects and interactions of stimulant medication use, time, and age group on regional apparent cortical thickness.ResultsA total of 32 male adolescents (aged mean±SD, 11.2±0.9 at baseline) and 24 men (aged mean±SD, 29.9±5.0 at baseline) were included that previously participated in the ePOD-MPH project. We found no evidence for long-term effects of stimulant medication use on ROI apparent cortical thickness. As expected, we did find age-by-time interaction effects in all ROIs (left prefrontal ROI: P=.002, right medial and posterior ROIs: P<.001), reflecting reductions in apparent cortical thickness in adolescents. Additionally, ADHD symptom severity (adolescents: P<.001, adults: P=.001) and anxiety symptoms (adolescents: P=0.03) were reduced, and lower change in ADHD symptoms was associated with higher medication use in adults (P=0.001).ConclusionWe found no evidence for long-term effects of stimulant-treatment for ADHD on apparent cortical thickness development in adolescents and adults. The identified age-dependent differences in apparent cortical thickness development are consistent with existing literature on typical cortical development.Summary statementThis prospective longitudinal study in male adolescents and adults found that stimulant medication does not modulate long-term apparent cortical thickness development.Key resultsIn this prospective longitudinal structural MRI study of 32 male adolescents and 24 men previously diagnosed with attention-deficit/hyperactivity disorder (ADHD), we found no evidence for long-term effects of stimulant medication on apparent cortical thickness development.We identified age-dependent patterns of cortical development, with reductions in apparent cortical thickness in adolescents only (P<.001 in all regions of interest).