Long-term effects of stimulant exposure on cerebral blood flow response to methylphenidate and behavior in attention-deficit hyperactivity disorder.
Stimulant prescription rates for attention deficit hyperactivity disorder (ADHD) are increasing, even though potential long-term effects on the developing brain have not been well-studied. A previous randomized clinical trial showed short-term age-dependent effects of stimulants on the DA system. We here assessed the long-term modifying effects of age-of-first-stimulant treatment on the human brain and behavior. 81 male adult ADHD patients were stratified into three groups: 1) early stimulant treatment (EST; <16 years of age) 2) late stimulant treatment (LST: ≥23 years of age) and 3) stimulant treatment naive (STN; no history of stimulant treatment). We used pharmacological magnetic resonance imaging (phMRI) to assess the cerebral blood flow (CBF) response to an oral methylphenidate challenge (MPH, 0.5 mg/kg), as an indirect measure of dopamine function in fronto-striatal areas. In addition, mood and anxiety scores, and recreational drug use were assessed. Baseline ACC CBF was lower in the EST than the STN group (p = 0.03), although CBF response to MPH was similar between the three groups (p = 0.23). ADHD symptom severity was higher in the STN group compared to the other groups (p < 0.01). In addition, the EST group reported more depressive symptoms (p = 0.04), but not anxiety (p = 0.26), and less recreational drug use (p = 0.04). In line with extensive pre-clinical data, our data suggest that early, but not late, stimulant treatment long-lastingly affects the human brain and behavior, possibly indicating fundamental changes in the dopamine system.
Department of Radiology, Academic Medical Center, University of Amsterdam, P.O. Box 22660, 1105, AZ, Amsterdam, the Netherlands. a.g.schrantee@amc.uva.nl.
Anouk
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Schrantee
Department of Radiology, Academic Medical Center, University of Amsterdam, P.O. Box 22660, 1105, AZ, Amsterdam, the Netherlands.
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Bouziane
Biomedical Imaging Group Rotterdam, Departments of Medical Informatics and Radiology, Erasmus MC, P.O. Box 2040, 3000, CA, Rotterdam, The Netherlands.
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Bron
Biomedical Imaging Group Rotterdam, Departments of Medical Informatics and Radiology, Erasmus MC, P.O. Box 2040, 3000, CA, Rotterdam, The Netherlands.
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Klein
Department of Radiology, Academic Medical Center, University of Amsterdam, P.O. Box 22660, 1105, AZ, Amsterdam, the Netherlands.|Department of Child- and Adolescent Psychiatry, Triversum, Kees Boekestraat 5, 1817, EZ, Alkmaar, The Netherlands.
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Bottelier
Expertise Center Adult ADHD, PsyQ, Psycho-Medical Programs, Carel Reinierszkade 197, 2593, HR, The Hague, The Netherlands.
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JJS
Kooij
Institute of Psychology, Leiden University, P.O. Box 9555, 2300, RB, Leiden, The Netherlands.|Department of Radiology, LUMC, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
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SARB
Rombouts
Department of Radiology, Academic Medical Center, University of Amsterdam, P.O. Box 22660, 1105, AZ, Amsterdam, the Netherlands.
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Reneman
D000328:Adult; D000339:Affect / Q000187:drug effects; D000367:Age Factors; D001289:Attention Deficit Disorder with Hyperactivity / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000254:growth & development / Q000503:physiopathology; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D019966:Substance-Related Disorders; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000697:Central Nervous System Stimulants; D008774:Methylphenidate
ADHD; Age; CBF; Methylphenidate; Stimulants; phMRI