Striatal dopamine transporter alterations in ADHD: pathophysiology or adaptation to psychostimulants? A meta-analysis

Previous exposure to ADHD medication influenced striatal dopamine transporter density, with lower density associated with lack of medication exposure.

“Meta-regression analysis further revealed that previous exposure to ADHD medication influenced striatal DAT density, with lower DAT density being associated with a lack of medication exposure (202).”

A meta-analysis of 9 PET and SPECT studies reported that striatal dopamine transporter density in patients with ADHD was 14% higher than in healthy controls.

“In a meta-analysis of 9 PET and SPECT studies, which included 169 patients with ADHD and 173 healthy controls, it was reported that striatal DAT density in patients with ADHD was 14% higher than in healthy controls (202).”

The correlation between medication exposure and striatal dopamine transporter density accounted for 48% of variance across studies, suggesting higher density in ADHD was a neuroadaptive response to stimulant exposure.

“As the correlation between medication exposure and striatal DAT density accounted for 48% of the variance across studies (202), it was suggested that the higher striatal DAT density in individuals with ADHD was a neuroadaptive response to stimulant exposure.”

Prefrontal stimulation has been shown to increase striatal dopamine, similar to amphetamines, which is typically reduced in ADHD.

“prefrontal stimulation has shown to increase striatal dopamine (Pogarell et al., 2007), similar to amphetamines, which is typically reduced in ADHD (Fusar-Poli et al., 2012).”

Potential longer-term efficacy could be the real advantage of tDCS over stimulant medication, whose effects are discontinued with discontinued drug administration and appear to wane in long-term continuous administration, presumably due to brain adaptation to the drug.

“potential longer-term efficacy could be the real advantage of tDCS over stimulant medication where effects are discontinued with discontinued drug administration and where effects appear to even wane in long-term continuous administration (Molina et al., 2009), presumably due to brain adaptation to the drug (Fusar-Poli et al., 2012).”

Such delayed consolidation effects reinforce the notion that brain self-regulation via NF affects neuroplasticity and may hence have unique longer-term efficacy compared to stimulant medication which does not affect neuroplasticity and may even lose efficacy over time, due to potential brain adaptation.

“Such delayed consolidation effects reinforce the notion that brain self-regulation via NF affects neuroplasticity and may hence have unique longer-term efficacy compared to stimulant medication which does not affect neuroplasticity and may even loose efficacy over time (Molina et al., 2009), due to potential brain adaptation (Fusar-Poli et al., 2012).”

Molecular imaging (PET/SPECT) meta-analytically points to increased dopamine transporter (DAT) density in the striatum in ADHD.

“molecular imaging (PET/SPECT), which, despite some inconsistencies, meta-analytically points to increased DA transporter (DAT) density in the striatum”

Striatal dopamine transporters are abnormally low in medication-naïve ADHD patients.

“which are abnormally low in medication-naïve ADHD patients (14).”

Long-term stimulant medication was associated with abnormally elevated striatal DAT levels.

“Our meta-regression analysis of positron emission tomography studies, on the other hand, showed that long-term stimulant medication was associated with abnormally elevated striatal DAT levels (14), which was also found in a prospective 1-year positron emission tomography study 86, 87, suggesting brain adaptation and tolerance to long-term stimulants.”