Methylphenidate-associated brain structural changes and neuroimaging predictors of treatment response in youth with ADHD: a systematic review.

Authors

Liesbeth Reneman, Zarah van der Pal, Daniëlle de Smidt, Shandra Bipat

Published in

NeuroImage. Clinical. Volume 52. Pages 104085. Nov 03, 2026. Epub Nov 03, 2026.

Abstract

Methylphenidate (MPH) is a psychostimulant widely prescribed to children with attention-deficit/hyperactivity disorder (ADHD). Although its clinical efficacy is well established, its lasting effects on the developing brain remain unclear.
This systematic review aimed to examine associations between long-term MPH treatment and brain structure in children and adolescents with ADHD using structural magnetic resonance imaging (sMRI) and diffusion tensor imaging (DTI), distinguishing longitudinal treatment-effect studies from cross-sectional medication-history comparisons and baseline neuroimaging predictors of treatment response.
A systematic search was conducted in MEDLINE and Embase databases. Studies were included if they investigated structural brain changes (gray matter volume, white matter integrity and cortical thickness) after at least four weeks of MPH treatment in children with ADHD. Data extraction and quality assessment were performed using the NIH quality assessment tool.
Eight studies met the inclusion criteria: three longitudinal studies using repeated MRI to assess within-subject treatment effects, two cross-sectional comparisons based on medication history, and three studies using baseline neuroimaging to predict subsequent treatment response. Greater putamen volume was associated with medication status ad volume with better treatment response in the cross-sectional and predictive analyses, while cortical effects were less consistent and mainly age-dependent in frontal areas. White matter findings were subtle and inconsistent across studies, and cortical thickness evidence-limited to one study-suggests short-term, possibly transient effects in children.
MPH treatment is associated l with age-dependent differences in brain structure in children and adolescents with ADHD; however, the limited number of included studies varied substantially in design, (cross-sectional and predictive studies alongside longitudinal treatment-effect studies), methodology, and reported outcomes, making firm causal conclusions difficult. Future research should prioritize larger, standardized, long-term longitudinal studies that account for developmental factors.

PMID:
42998542
Bibliographic data and abstract were imported from PubMed on 08 Nov 2026.

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