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Title: Effects of Atomoxetine and Methylphenidate on functional brain activation in medication-naive children with Attention Deficit Hyperactivity Disorder
Author: Cubillo, Ana
Awarding Body: King's College London (University of London)
Current Institution: King's College London (University of London)
Date of Award: 2013
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The present functional magnetic resonance imaging (MRI) study compared the effects of two commonly prescribed medications for Attention Deficit Hyperactivity Disorder (ADHD), the stimulant methylphenidate (MPH), and the non-stimulant Atomoxetine (ATX) in ADHD. Brain activation and task performance during motor inhibition (Stop), time discrimination (TD) and working memory (WM) tasks were compared in 20 medication-naive ADHD boys (10-17 years-old) after a single dose of MPH (0.3mg/kg), ATX (Img/kg) or placebo (Vit C, 50mg) using a randomized, double-blind, placebo-controlled desiga To test for potential normalization effects, brain activation in patients under each drug was compared to that of 20 age-matched unmedicated healthy boys. Both drugs showed task-dependent drug-specific and shared effects. Performance-wise, only MPH improved inhibitory speed and reduced TD errors in patients, while both drugs improved WM. MPH relative to ATX upregulated and normalised underactivatkm in patients relative to controls in right VLPFC and cerebellar/occipital areas during motor inhibition, in left IFC during TD and WM and in left putamen and SMA/ACC during TD. During WM, ATX showed drug-specific upregulation and normalisation effects relative to MPH in right DLPFC, which was reduced in patients relative to controls. Shared effects were normalisation of underactivation in patients relative to controls in left VLPFC during motor inhibition and in right VLPFC during TD. During WM, both drugs enhanced performance-associated fronto-temporo-striatal activation and deactivated default-mode network regions in patients relative to controls. In conclusion, ATX and MPH have task-dependent drug-specific effects on task-relevant prefrontal regions, suggesting different mechanisms of action despite their shared prefrontal catecholaminergic effects. Their differential prefrontal lateralisation suggests potentially stronger effects of MPH on left-lateralised dopaminergic networks, and of ATX on right-lateralised noradrenergic networks. Their shared effects were not restricted to prefrontal regions or task-positive networks, but extended to default-mode networks, suggesting they act on wider dopaminergic and noradrenergic neural networks.
Supervisor: Rubia, Katya ; Smith, Anna Belinda Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available