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

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.MethodsThirteen 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.ResultsOn-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).ConclusionOur 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.

A systematic review of the potential effects of medications and drugs of abuse on dopamine transporter imaging using [123I]I-FP-CIT SPECT in routine practice

“…Interestingly, more recent studies have also shown similar results. The use of methylphenidate was associated with a 30% decrease in striatal [ 123 I]I-ß-CIT binding in 13 ADHD patients [ 60 ]. Only 2.5 h after oral intake of 30 mg methylphenidate, the striatal binding of [ 123 I]I-FP-CIT was reduced by 43% in 13 patients with traumatic brain injury [ 61 ].…”

Consequences of Acute or Chronic Methylphenidate Exposure Using Ex Vivo Neurochemistry and In Vivo Electrophysiology in the Prefrontal Cortex and Striatum of Rats

“…Furthermore, imaging studies in humans [ 76 , 77 , 78 , 79 , 80 , 81 ] have also observed significant effects of MPH on DAT and NET availability. In patients with ADHD, MPH treatment decreases DAT availability [ 82 , 83 , 84 , 85 ], likely indicating altered baseline DAT levels in these patients [ 24 , 83 ], although this is not always observed [ 81 ]. Finally, long-term MPH was shown to alter dopamine levels in striatal regions of patients with ADHD [ 86 ], highlighting altered dopamine neurotransmission following chronic MPH exposure.…”