Psychostimulant treatment and the developing cortex in attention deficit hyperactivity disorder

Abstract

Objective: While there has been considerable concern over possible adverse effects of psychostimulants on brain development, this issue has not been examined in a prospective study. The authors sought to determine prospectively whether psychostimulant treatment for attention deficit hyperactivity disorder (ADHD) was associated with differences in the development of the cerebral cortex during adolescence.

Method: Change in cortical thickness was estimated from two neuroanatomic MRI scans in 43 youths with ADHD. The mean age at the first scan was 12.5 years, and at the second scan, 16.4 years. Nineteen patients not treated with psychostimulants between the scans were compared with an age-matched group of 24 patients who were treated with psychostimulants. Further comparison was made against a template derived from 620 scans of 294 typically developing youths without ADHD.

Results: Adolescents taking psychostimulants differed from those not taking psychostimulants in the rate of change of the cortical thickness in the right motor strip, the left middle/inferior frontal gyrus, and the right parieto-occipital region. The group difference was due to more rapid cortical thinning in the group not taking psychostimulants (mean cortical thinning of 0.16 mm/year [SD=0.17], compared with 0.03 mm/year [SD=0.11] in the group taking psychostimulants). Comparison against the typically developing cohort without ADHD showed that cortical thinning in the group not taking psychostimulants was in excess of age-appropriate rates. The treatment groups did not differ in clinical outcome, however.

Conclusions: These findings show no evidence that psychostimulants were associated with slowing of overall growth of the cortical mantle.

Figures

Figure 1

Brain templates (leftmost) show the regions where the ADHD groups had a significantly different rate of cortical growth. The rate of change in raw cortical thickness in these regions is shown (middle column). The final column shows the baseline and endpoint raw cortical thickness for each ADHD group and the age expected values for a typically developing adolescent. The group ‘on’ psychostimulants is shown in blue, the group ‘off’ psychostimulants in red. The expected cortical thickness at time 1 (age~ 12.5 yrs) and time 2 (~age 16.4) for a typically developing group is given in green.