Medications and the White Matter

ADHD has been associated with changes in whole and regional brain volumes, cortical thickness (CT) and white matter microstructure. Here we investigated whether eventual differences in these brain measures were related to stimulant treatment suing data from the NeuroIMAGE cohort study. Participants with ADHD showed decreased medial temporal CT in both left and right hemispheres. These differences were present across different ages and were associated with symptoms of hyperactivity and prosocial behavior. There were no age-by-diagnosis interaction effects. None of the stimulant treatment parameters predicted CT within ADHD. Whole brain and regional brain volumes were also unrelated to stimulant treatment history, in contrast to findings from meta-analyses.

Further, we analyzed white matter integrity in five white matter tracts (orbitofrontal-striatal, orbitofrontal-amygdalar, amygdalar-striatal, dorsolateral-prefrontal-striatal and medial prefrontal-striatal). After correction for multiple testing, participants with ADHD showed reduced fractional anisotropy (FA) in the orbitofrontal-striatal pathway. Within the ADHD group, higher cumulative stimulant intake was associated with lower MD in the same pathway, but not with FA. The association between stimulant treatment and orbitofrontal-striatal MD was of modest effect size. Our findings are compatible with stimulant treatment enhancing orbitofrontal-striatal white matter connectivity, and emphasize the importance of the orbitofrontal cortex and its connections in ADHD.

References

• Schweren LJ, Hartman CA, Heslenfeld DJ, van der Meer D, Franke B, Oosterlaan J, Buitelaar JK, Faraone SV, Hoekstra PJ. Thinner Medial Temporal Cortex in Adolescents With Attention-Deficit/Hyperactivity Disorder and the Effects of Stimulants. J Am Acad Child Adolesc Psychiatry. 2015 Aug;54(8):660-7.
• Schweren LJ, Hartman CA, Zwiers MP, Heslenfeld DJ, Franke B, Oosterlaan J, Buitelaar JK, Hoekstra PJ. Stimulant treatment history predicts frontal-striatal structural connectivity in adolescents with attention-deficit/hyperactivity disorder. Eur Neuropsychopharmacol. 2016 Apr;26(4):674-83.