Stimulants Medication Effects on the ADHD Brain

I will review the evidence for stimulant effects on brain chemistry, structure and function in ADHD.

Positron emission tomography studies in adult ADHD shows that acute effects of stimulants are associated with enhanced striatal dopamine release, with however, inconsistent findings of whether this is enhanced, similar or blunted in ADHD relative to healthy controls. Long-term stimulant medication seems to be associated with abnormally elevated striatal dopamine transporters, which are reduced in medication-naïve patients with ADHD, suggesting brain adaptation to stimulants (Fusar-Poli et al., 2012). Recent retrospective, prospective and meta-regression analyses suggest that stimulants have no effect on brain structure or brain development (Norman et al., 2016, Hoogman et al., 2017). In fMRI studies, single dose and longer-term effects seem to be associated with upregulation/normalisation of inferior and dorsolateral fronto-striatal activation and connectivity as well as with enhanced deactivation and anticorrelation of the default mode network with task-positive networks, although downregulation has also been observed in some studies. Stimulants thus appear to target the key neurofunctional pathology of ADHD, of poor task-relevant fronto-striatal activation and connectivity and poor deactivation of the DMN.

References

Fusar-Poli, P., Rubia, K., Rossi, G., Sartori, G., Ballotin, U. 2012. Dopamine transporter alterations in ADHD: pathophysiology or adaptation to psychostimulants? a meta-analysis. American Journal of Psychiatry 169, 264 -72.

Hoogman M et al., (2017) Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional mega-analysis. Lancet Psychiatry 4(4):310-319

Norman LJ, Carlisi C, Lukito S, Hart H, Mataix-Cols D, Radua J, Rubia K. (2016) tructural and Functional Brain Abnormalities in Attention Deficit/ Hyperactivity Disorder and Obsessive-Compulsive Disorder: A Comparative Meta-analysis. JAMA Psychiatry 73(8):815-825

Rubia, K., Alzamora, A., Cubillo, A., Smith, A.B., Radua, J., Brammer, M.J. 2014. Effects of stimulants on brain function in ADHD: a systematic review and meta-analysis. Biol Psychiatry; 76(8):616-28.