Responsivity of the Striatal Dopamine System to Methylphenidate-A Within-Subject I-123-beta-CIT-SPECT Study in Male Children and Adolescents With Attention-Deficit/Hyperactivity Disorder

Hans Christoph Aster*, Marcel Romanos, Susanne Walitza, Manfred Gerlach, Andreas Mühlberger, Albert Rizzo, Marta Andreatta, Natalie Hasenauer, Philipp E. Hartrampf, Kai Nerlich, Christoph Reiners, Reinhard Lorenz, Andreas K. Buck, Lorenz Deserno

*Corresponding author for this work

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Abstract

Background: Methylphenidate (MPH) is the first-line pharmacological treatment of attention-deficit/hyperactivity disorder (ADHD). MPH binds to the dopamine (DA) transporter (DAT), which has high density in the striatum. Assessments of the striatal dopamine transporter by single positron emission computed tomography (SPECT) in childhood and adolescent patients are rare but can provide insight on how the effects of MPH affect DAT availability. The aim of our within-subject study was to investigate the effect of MPH on DAT availability and how responsivity to MPH in DAT availability is linked to clinical symptoms and cognitive functioning. Methods: Thirteen adolescent male patients (9–16 years) with a diagnosis of ADHD according to the DSM-IV and long-term stimulant medication (for at least 6 months) with MPH were assessed twice within 7 days using SPECT after application of I-123-β-CIT to examine DAT binding potential (DAT BP). SPECT measures took place in an on- and off-MPH status balanced for order across participants. A virtual reality continuous performance test was performed at each time point. Further clinical symptoms were assessed for baseline off-MPH. Results: On-MPH status was associated with a highly significant change (−29.9%) of striatal DAT BP as compared to off-MPH (t = −4.12, p = 0.002). A more pronounced change in striatal DAT BP was associated with higher off-MPH attentional and externalizing symptom ratings (Pearson r = 0.68, p = 0.01). Striatal DAT BP off-MPH, but not on-MPH, was associated with higher symptom ratings (Pearson r = 0.56, p = 0.04). Conclusion: Our findings corroborate previous reports from mainly adult samples that MPH changes striatal DAT BP availability and suggest higher off-MPH DAT BP, likely reflecting low baseline DA levels, as a marker of symptom severity.

Original languageEnglish
Article number804730
JournalFrontiers in Psychiatry
Volume13
DOIs
Publication statusPublished - 14 Apr 2022

Bibliographical note

Funding Information:
This study was supported by a grant from the Interdisciplinary Centre of Clinical Research at the Medical Faculty of the University of Würzburg (Untersuchungen des Dopamin-Transporters mittels TC-99m-TRODAT-1-SPECT bei Jugendlichen mit ADHS) and by the German Research Foundation (DFG) as part of KFO 125 Attention Deficit/Hyperactivity Syndrome (ADHD): Molecular Pathogenesis and Endophenotypes in the Course of Treatment, Project Number 5397423. H-CA was supported by a Clinician Scientist Program at the Interdisciplinary Centre of Clinical Research at the Medical Faculty of the University of Würzburg. LD was supported by the IFB Adiposity Diseases, Federal Ministry of Education and Research (BMBF), Germany, GN: 01EO150, and the German Research Foundation (DFG) as part of the Collaborative Research Centre 265 Losing and Regaining Control over drug intake (402170461, Project A02).

Publisher Copyright: Copyright © 2022 Aster, Romanos, Walitza, Gerlach, Mühlberger, Rizzo, Andreatta, Hasenauer, Hartrampf, Nerlich, Reiners, Lorenz, Buck and Deserno.

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