The Association with Quantitative Response to Attention-Deficit/Hyperactivity Disorder Medication of the Previously Identified Neurodevelopmental Network Genes.

Objective

A recent pharmacoimaging study suggested that methylphenidate (MPH) and atomoxetine (ATX) might have common mechanisms for the treatment of attention-deficit/hyperactivity disorder (ADHD). Previous pharmacogenetic studies have by and large only involved genes in neurotransmitter systems, which accounted for very small variances. Therefore, this study aimed to investigate whether the neurodevelopmental genes identified in a prior ADHD etiology Genome-Wide Association Study (GWAS) could predict patients' responses to MPH and ATX, given the aforementioned mechanisms of action.

Methods

For our sample of 241 patients with ADHD, we assessed the change in the ADHD rating scale (ADHD-RS) total symptom scores from baseline to the end of the 12th week of treatment with either MPH or ATX. We performed association analyses at the genetic single-marker, gene-based, set-based, and GWAS-based polygenic levels.

Results

In our analyses, neither single nucleotide polymorphism (SNP) nor gene-level analyses yielded significant markers associated with the change in the ADHD-RS score after multiple comparison correction. The polygenic risk score model, which was based on SNPs associated with ADHD etiology at a threshold of p ≤ 0.0001 in a recent Han Chinese GWAS, predicted symptomatic improvement with ADHD medication (p = 0.018, R2 = 0.023).

Conclusion

Our results provide new evidence for a small influence of neurodevelopmental genes on the efficacy of medications for ADHD.