Is increased D2 receptor availability associated with response to stimulant medication in ADHD

Abstract

The purpose of this study was to estimate striatal dopamine (D2) receptor availability in non-drug treated children with attention-deficit-hyperactivity disorder (ADHD) before and after methylphenidate therapy, and to examine correlations between severity of symptoms and response rates to stimulant medication with levels of striatal D2 receptor binding. Nine children (six males, three females; mean age 9.8 years, SD 2.3 years) with ADHD participated. All underwent iodobenzamide (123I IBZM) brain SPECT within 2 hours following intravenous injection of 123I IBZM before and 3 months after methylphenidate therapy. A semiquantitative approach was used to generate indices of specific D2 receptor binding in the basal ganglia. Specific binding ratios at baseline were higher than the previously reported specific binding values obtained in studies using young healthy adults. D2 availability reduced significantly (paired t-test, p<0.05) as a function of methylphenidate therapy in patients with ADHD in all four regions of the striatum. When the relation between therapy response and D2 availability was investigated, we observed that the higher the baseline D2 levels were, the higher the response rate was (detected as the percentage reduction of hyperactivity scores and Conners Teacher Rating Scale scores), while no such trend was observed between the initial D2 binding levels and the response in attention-deficit scores. Results indicate that in non-drug treated children with ADHD, higher D2 receptor availability is observed at baseline which is down-regulated back to reported near-normal values after methylphenidate therapy. The effect of methylphenidate on D2 receptor levels in patients with ADHD is similar to that observed in healthy adults; a down-regulation phenomenon within 0 to 30%. In addition, initially higher values of D2 availability seem to indicate better response to methylphenidate therapy in ADHD.

Availability of Striatal Dopamine Transporter in Healthy Individuals With and Without a Family History of ADHD

“…In the imaging studies, various parameters of the dopaminergic system have been measured, including DAT (Spencer et al, 2005), dopamine D 2 receptors (Lou et al, 2004), dopamine synthesis (Ernst et al, 1999), and extracellular dopamine levels (Ilgin, Senol, Gucuyener, Gokcora, & Sener, 2001). The most widely investigated parameter has been the DAT, especially variations in the density of presynaptic DATs.…”

Regional brain volume predicts response to methylphenidate treatment in individuals with ADHD

“…Patients with ADHD with higher striatal dopamine transporter availability show a better response to methylphenidate treatment [15]. Further, striatal dopamine receptor (D2) availability is positively associated with methylphenidate response [73]. In parallel, larger GM volumes are believed to be related to an increased density of neurons and more synapses in the local brain region [74].…”

Risperidone-to-methylphenidate switch reaction in children: three cases

“…One study conducted with humans found that risperidone pretreatment attenuated discriminative-stimulus effects of d-amphetamine and some self-reported behavioural effects (Rush et al, 2003), which may be considered as already-existing evidence of altered stimulant response after atypical antipsychotic exposure. Recent evidence by SPECT imaging suggests that, in children with ADHD, a positive clinical response with methylphenidate corresponds to down-regulation of the post-synaptic dopamine receptors and down-regulation of the dopamine transporter in the striatal system (Ilgin et al, 2001;Moll et al, 2001;Vles et al, 2003). In contrast, atypical neuroleptics up-regulate dopamine receptors (Silvestri et al, 2000;Tarazi et al, 2001).…”