Article

Long-term stimulant treatment affects brain dopamine transporter level in patients with attention deficit hyperactive disorder

Department of Radiology, Stony Brook University, Stony Brook, New York, United States of America
PLoS ONE (Impact Factor: 3.23). 05/2013; 8(5):e63023. DOI: 10.1371/journal.pone.0063023
Source: PubMed

ABSTRACT Brain dopamine dysfunction in attention deficit/hyperactivity disorder (ADHD) could explain why stimulant medications, which increase dopamine signaling, are therapeutically beneficial. However while the acute increases in dopamine induced by stimulant medications have been associated with symptom improvement in ADHD the chronic effects have not been investigated.
We used positron emission tomography and [(11)C]cocaine (dopamine transporter radioligand) to measure dopamine transporter availability in the brains of 18 never-medicated adult ADHD subjects prior to and after 12 months of treatment with methylphenidate and in 11 controls who were also scanned twice at 12 months interval but without stimulant medication. Dopamine transporter availability was quantified as non-displaceable binding potential using a kinetic model for reversible ligands.
TWELVE MONTHS OF METHYLPHENIDATE TREATMENT INCREASED STRIATAL DOPAMINE TRANSPORTER AVAILABILITY IN ADHD (CAUDATE, PUTAMEN AND VENTRAL STRIATUM: +24%, p<0.01); whereas there were no changes in control subjects retested at 12-month interval. Comparisons between controls and ADHD participants revealed no significant difference in dopamine transporter availability prior to treatment but showed higher dopamine transporter availability in ADHD participants than control after long-term treatment (caudate: p<0.007; putamen: p<0.005).
Upregulation of dopamine transporter availability during long-term treatment with methylphenidate may decrease treatment efficacy and exacerbate symptoms while not under the effects of the medication. Our findings also suggest that the discrepancies in the literature regarding dopamine transporter availability in ADHD participants (some studies reporting increases, other no changes and other decreases) may reflect, in part, differences in treatment histories.

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    • "Stimulant medication has emerged as the primary treatment for the core symptoms of ADHD, however some children do not respond to medication or suffer from side effects such as headache, dizziness, insomnia, anxiety and gastroenterological problems (Graham et al 2011). In addition to that, the long-lasting effects of both stimulant medication and behavior therapy are uncertain, with some studies reporting limited effects (Wang et al 2013; Molina et al 2009). Neurofeedback (NF) is a promising alternative treatment for ADHD (Arns et al 2014; Loo and Makeig 2012). "
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    • "One further shortcoming relates to the use of MPH medications particularly in ADHD versus ASD. Although medications were discontinued at least 48 h prior to testing, research has shown that chronic MPH application is able to upregulate striatal dopamine turnover (Wang et al., 2013). Therefore, MPH treatment history could have biased the current findings of differential striatum reactivity in ADHD versus the two other study groups. "
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    • "However, recent large-scale studies and meta-analyses have demonstrated limitations of these treatments. For example, limited long-term effects of stimulant medication (possibly the result of an up-regulation of the Dopamine Transporter (DAT) (Wang et al., 2013)) and behaviour therapy have been reported (Molina et al., "
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