Striatal Dopamine Transporter Alterations in ADHD: Pathophysiology or Adaptation to Psychostimulants? A Meta-Analysis

Background: Striatal dopamine transporter abnormalities are thought to underlie the pathophysiology and psychostimulant treatment of attention deficit hyperactivity disorder (ADHD). However, individual studies using single photon emission tomography (SPEC) or positron emission tomography (PET) have yielded inconsistent results, i.e., both high and low striatal dopamine transporter levels. Method: Nine SPECT and PET studies investigating striatal dopamine transporter density in ADHD patients (N=169) and age-, gender-, and IQ-matched healthy comparison subjects (N=173) were included in a quantitative meta-analysis. Binding potentials in the striatum and demographic, clinical, and methodological variables were extracted from each publication or obtained directly from authors. Hedges' g was used as a measure of effect size in an analysis using Comprehensive Meta-Analysis software. Publication bias was assessed with funnel plots and Egger's intercept. Heterogeneity was addressed with the Q statistic and I-2 index. Results: Striatal dopamine transporter density was 14% higher on average in the ADHD group than in the healthy comparison group. However, heterogeneity across studies was large and statistically significant. Meta-regression analyses showed that the percentage of subjects without exposure to psychostimulants was negatively correlated with dopamine transporter density; density was higher in patients with previous medication exposure and lower in medication-naive patients. There was no moderating effect for age, comorbidity, gender, year of publication, or imaging technique. There was no publication bias, and sensitivity analysis confirmed robustness of the results. Conclusions: Striatal dopamine transporter density in ADHD appears to depend on previous psychostimulant exposure, with lower density in drug-naive subjects and higher density in previously medicated patients.