ADHD pharmacogenetics across the life cycle: New findings and perspectives

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a complex and heterogeneous disorder, affecting individuals across the life cycle. Although its etiology is not yet completely understood, genetics plays a substantial role. Pharmacological treatment is considered effective and safe for children and adults, but there is considerable inter-individual variability among patients regarding response to medication, required doses, and adverse events. We present here a systematic review of the literature on ADHD pharmacogenetics to provide a critical discussion of the existent findings, new approaches, limitations, and recommendations for future research. Our main findings are: first, the number of studies continues to grow, making ADHD one of the mental health areas with more pharmacogenetic studies. Second, there has been a focus shift on ADHD pharmacogenetic studies in the last years. There is an increasing number of studies assessing gene-gene and gene-environment interactions, using genomewide association approaches, neuroimaging, and assessing pharmacokinetic properties. Third and most importantly, the heterogeneity in methodological strategies employed by different studies remains impressive. The question whether pharmacogenetics studies of ADHD will improve clinical management by shifting from trial-and-error approach to a pharmacological regimen that takes into account the individual variability remains unanswered.

Noninvasive Brain Stimulation in Pediatric Attention-Deficit Hyperactivity Disorder (ADHD)

“…Current pharmacotherapy is not reliably guided by any disease-specific biomarkers or diagnostic tests, though advances in pharmacognetics may prove useful with further study 85 . It is possible that neurophysiological abnormalities assessed by TMS could also be used for this purpose 86 .…”

Attention-Deficit Hyperactivity Disorder and Pharmacotherapy—Past, Present, and Future: A Review of the Changing Landscape of Drug Therapy

“…The majority of PGx-based studies have focused on existing ADHD medications, primarily methylphenidate, with the goal of identifying specific biomarkers of drug response, which are reviewed briefly here (see also Bruxel et al , 2014 56 ). One exception to this approach is a study from our group, which has used results from genomics analyses to identify novel drug targets for a genome-stratified ADHD sub-cohort.…”

“…This would seem substantiated by a meta-analysis by Kambeitz et al, 2014 (n=1572) 60 , which found no evidence of a genotype-specific response to methylphenidate treatment (P>0.5). Similarly, VNTRs in the dopamine receptor D4 (DRD4) have been studied, again with no strong evidence of a genotype-specific response to methylphenidate 56 .…”

Does serotonin deficit mediate susceptibility to ADHD?

“…Candidate genes each with 'small effect' might be by interacting with each other imposing an additive effect on ADHD etiology. In the last five years (2010)(2011)(2012)(2013)(2014)) several pharmacogenetic studies have been published with regard to gene x gene and gene x environment interactions (Bruxel et al, 2014).…”