title: The age-dependent effects of a single-dose methylphenidate challenge on cerebral perfusion in patients with attention-deficit/hyperactivity disorder.
abstract: Methylphenidate (MPH) is a stimulant drug and an effective treatment for attention-deficit/hyperactivity disorder (ADHD) in both children and adults. Pre-clinical studies suggest that the response to stimulants is dependent on age, which may reflect the ontogeny of the dopamine (DA) system, which continues to develop throughout childhood and adolescence. Therefore, the aim of this study was to investigate the modulating effect of age on the cerebral blood flow (CBF) response to MPH in stimulant treatment-naive children and adults with ADHD. Ninety-eight stimulant treatment-naive male pediatric (10-12 years) and adult (23-40 years) patients with ADHD were included in this study. The CBF response to an acute challenge with MPH (0.5 mg/kg) was measured using arterial spin labeling (ASL) pharmacological magnetic resonance imaging, as a proxy for DA function. Region-of-interest (ROI) analyses were carried out for the striatum, thalamus and medial prefrontal cortex and in addition voxel-wise analyses were conducted. An acute challenge with MPH decreased CBF in both children and adults in cortical areas, although to a greater extent in adults. In contrast, ROI analyses showed that MPH decreased thalamic CBF only in children, but not adults. Our findings highlight the importance of taking the developmental perspective into account when studying the effects of stimulants in ADHD patients.
authors.affiliation: Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Amsterdam Brain and Cognition, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Schrantee
authors.affiliation: Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
authors.forename: Hjmm
authors.initials: H
authors.lastname: Mutsaerts
authors.affiliation: Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Bouziane
authors.affiliation: Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Hgh
authors.initials: H
authors.lastname: Tamminga
authors.affiliation: Department of Child- and Adolescent Psychiatry, Triversum, Alkmaar, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: Bottelier
authors.affiliation: Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Amsterdam Brain and Cognition, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Reneman
mesh_terms: D000328:Adult; D000367:Age Factors; D001289:Attention Deficit Disorder with Hyperactivity / Q000000981:diagnostic imaging / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002648:Child; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000494:pharmacology*; D017072:Neostriatum / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects; D017397:Prefrontal Cortex / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects*; D013113:Spin Labels; D013788:Thalamus / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000697:Central Nervous System Stimulants; D013113:Spin Labels; D008774:Methylphenidate
keywords: ADHD; Age; Arterial spin labeling; Cerebral blood flow; Dopamine; Methylphenidate