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Review Article

Effect of Psychostimulants on Brain Structure and Function in ADHD: A Qualitative Literature Review of Magnetic Resonance Imaging-Based Neuroimaging Studies

Thomas J. Spencer, MD; Ariel Brown, PhD; Larry J. Seidman, PhD; Eve M. Valera, PhD; Nikos Makris, MD; Alexandra Lomedico, BA; Stephen V. Faraone, PhD; and Joseph Biederman, MD

Published: September 15, 2013

Article Abstract

Objective: To evaluate the impact of therapeutic oral doses of stimulants on the brains of ADHD subjects as measured by magnetic resonance imaging (MRI)-based neuroimaging studies (morphometric, functional, spectroscopy).

Data Sources: We searched PubMed and ScienceDirect through the end of calendar year 2011 using the keywords (1) psychostimulants or methylphenidate or amphetamine, and (2) neuroimaging or MRI or fMRI, and (3) ADHD or ADD or attention-deficit/hyperactivity disorder or attention deficit hyperactivity disorder.

Study Selection: We included only English language articles with new data from case-control or placebo controlled studies that examined attention-deficit/hyperactivity disorder (ADHD) subjects on and off psychostimulants (as well as 5 relevant review articles).

Data Extraction: We combined details of study design and medication effects in each imaging modality.

Results: We found 29 published studies that met our criteria. These included 6 structural MRI, 20 functional MRI studies, and 3 spectroscopy studies. Methods varied widely in terms of design, analytic technique, and regions of the brain investigated. Despite heterogeneity in methods, however, results were consistent. With only a few exceptions, the data on the effect of therapeutic oral doses of stimulant medication suggest attenuation of structural and functional alterations found in unmedicated ADHD subjects relative to findings in controls.

Conclusions: Despite the inherent limitations and heterogeneity of the extant MRI literature, our review suggests that therapeutic oral doses of stimulants decrease alterations in brain structure and function in subjects with ADHD relative to unmedicated subjects and controls. These medication-associated brain effects parallel, and may underlie, the well-established clinical benefits.

J Clin Psychiatry 2013;74(9):902-917

Submitted: November 15, 2012; accepted April 19, 2013 (doi:10.4088/JCP.12r08287).

Corresponding author: Thomas J. Spencer, MD, Massachusetts General Hospital, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, 55 Fruit St-WRN 705, Boston, MA 02114 (

Volume: 74

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