Effects of oral methylphenidate on [18F]fallypride binding in healthy volunteers and adults with attention-deficit hyperactivity disorder (ADHD)

Abstract

Methylphenidate (MPH) improves performance on tests of prefrontal cognitive functioning in healthy volunteers and adults with ADHD. This study assessed increases of dopamine following a single dose of oral MPH, dopamine D2/D3 receptor availability in adult ADHD patients compared to healthy controls and relationships between dopamine activity, ADHD symptom severity and prefrontal cognitive functioning. 16 adults with ADHD and 16 matched controls were scanned with positron emission tomography (PET) and [18F]fallypride, a high-affinity D2/D3 receptor radiotracer, after a single oral dose of MPH (0.5mg/kg) or placebo in counter-blanaced order. [18F]fallypride binding potentials (BPs) in regions manually defined on magnetic resonance images were calculated using a reference tissue model. Selected CANTAB tasks were administered on both sessions. MPH displaced [18F]fallypride in all striatal sub-regions, globus pallidus and substantia nigra (SN). This effect was similar in patients and controls. Baseline BP in the pre-commissural caudate correlated negatively with attention deficit symptoms and total errors in SWM. BP changes in the SN following MPH correlated positively with baseline performance on RVIP and SWM, and with improved SWM performance following MPH. (All results p<0.01). Our results support a continuum model of dysregulations of the dopamine system and cognitive deficits in ADHD and a specific role of the SN in mediating cognitive enhancing effects of MPH.