Methylphenidate induced dopamine increases in striatum and temporal and frontal cortices predicts response to treatment in ADHD

Objectives Stimulant medications, which are effective treatments for ADHD, acutely enhance dopamine (DA) signaling in the brain. However the relationship between DA increases and the response to treatment has not been investigated. Here we assess if the variability in response to stimulant treatment in ADHD reflect variability in brain DA responses.

Methods Twenty ADHD adults who had been treated for 1 year with oral methylphenidate (MP) were studied. Subjects were tested with PET and [11C]raclopride after placebo and after intravenous methylphenidate 24 hours after treatment with oral MP was discontinued. Dopamine release was quantified as the difference in [11C]raclopride’s specific binding (non displaceable binding potential; BPND) between placebo and intravenous methylphenidate. Therapeutic response to MP was evaluated as the differences in scores of inattention and hyperactivity prior to treatment and while on oral MP.

Results Intravenous methylphenidate significantly decreased BPND in striatum and prefrontal and temporal cortices (SPM pc < 0.05). The decreases in BPND induced by intravenous methylphenidate in ventral striatum, prefrontal (BA 9, BA 10, BA 46) and temporal cortices (BA 21, BA 22) were positively correlated with improvement in symptoms of inattention with oral MP treatment (SPM voxel wise correlation pc < 0.05).

Conclusions This suggests that acute enhancement of dopamine signaling by MP in ventral striatum (brain region involved with motivation and reward), prefrontal (region involved with executive function) and temporal cortex (region involved in perceptive attention allocation) are involved in its therapeutic effects.

Research Support Intramural Research Program of the NI