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White Matter by Diffusion MRI Following Methylphenidate Treatment: A Randomized Control Trial in Males with
Cheima Bouziane1, Olena G Filatova1, Anouk Schrantee1
1From the Departments of Radiology and Nuclear Medicine and Biomedical Engineering and Physics, Amsterdam University Medical Centers, location AMC, University of Amsterdam, G1-222 Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands (C.B., A.S., M.W.A.C., F.M.V., L.R.); Department of Imaging Physics, Delft University of Technology, Delft, the Netherlands (O.G.F., F.M.V.); and Amsterdam Neuroscience, Amsterdam, the Netherlands (A.S., L.R.).
Abstract:
BackgroundMethylphenidate (MPH) is highly effective in treating attention-deficit/hyperactivity disorder (ADHD). However, not much is known about its effect on the development of human brain white matter (WM).PurposeTo determine whether MPH modulates WM microstructure in an age-dependent fashion in a randomized double-blind placebo-controlled trial (Effects of Psychotropic Medication on Brain Development-Methylphenidate, or ePOD-MPH) among ADHD referral centers between October 13, 2011, and June 15, 2015, by using diffusion-tensor imaging (DTI).Materials and MethodsIn this prospective study (NTR3103 and NL34509.000.10), 50 stimulant treatment-naive boys and 49 young adult men diagnosed with ADHD (all types) according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria were randomized to undergo treatment with MPH or placebo for 16 weeks. Before and 1 week after treatment cessation, study participants underwent MRI, including DTI. The outcome measure was change in fractional anisotropy (FA), which was assessed in three regions of interest (ROIs), as well as in a voxel-based analysis in brain WM. Data were analyzed by using intention-to-treat linear mixed models for ROI analysis and a permutation-based method for voxel-based analysis with family-wise error correction.ResultsFifty boys (n = 25 MPH group, n = 25 placebo group; age range, 10-12 years) and 48 men (n = 24 MPH group, n = 24 placebo group; age range, 23-40 years) were included. ROI analysis of FA yielded no main effect of time in any of the conditions. However, voxel-based analysis revealed significant (P < .05) time-by-medication-by-age interaction effects in several association tracts of the left hemisphere, as well as in the lateral aspect of the truncus of the corpus callosum, due to greater increase in FA (standardized effect size, 5.25) in MPH-treated boys. Similar changes were not present in boys receiving a placebo, nor in adult men.ConclusionFour months of treatment with methylphenidate affects specific tracts in brain white matter in boys with attention-deficit/hyperactivity disorder. These effects seem to be age dependent, because they were not observed in adults treated with methylphenidate.© RSNA, 2019Online supplemental material is available for this article.
Insights
Methylphenidate (MPH) treatment for attention-deficit/hyperactivity disorder (ADHD) in boys aged 10-12 significantly impacts white matter development. These age-dependent effects on brain white matter tracts were not observed in adult men with ADHD.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Psychiatry
Background:
- Methylphenidate (MPH) is a primary treatment for attention-deficit/hyperactivity disorder (ADHD).
- Limited understanding exists regarding MPH's impact on human brain white matter (WM) development.
- This study investigates MPH's age-dependent effects on WM microstructure.
Purpose of the Study:
- To determine if methylphenidate (MPH) modulates white matter (WM) microstructure in an age-dependent manner.
- To assess changes in WM microstructure using diffusion-tensor imaging (DTI) in boys and adult men with ADHD.
- To conduct a randomized double-blind placebo-controlled trial (ePOD-MPH) to evaluate these effects.
Main Methods:
- A prospective, randomized double-blind placebo-controlled trial involving stimulant-naive boys (10-12 years) and young adult men (23-40 years) with ADHD.
- Participants received either MPH or placebo for 16 weeks, with MRI and DTI scans before and after treatment.
- Analysis focused on fractional anisotropy (FA) changes in white matter using region-of-interest (ROI) and voxel-based analyses.
Main Results:
- Voxel-based analysis revealed significant time-by-medication-by-age interaction effects in specific left-hemisphere association tracts and the corpus callosum in MPH-treated boys.
- MPH-treated boys showed a greater increase in fractional anisotropy (FA) in these tracts compared to placebo boys.
- No similar age-dependent WM microstructure changes were observed in adult men treated with MPH or in placebo groups.
Conclusions:
- Four months of methylphenidate treatment influences specific brain white matter tracts in boys with ADHD.
- The observed effects on white matter microstructure are age-dependent.
- These findings suggest that MPH's impact on brain development may differ between prepubertal boys and adult men with ADHD.
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