A Current Update on ADHD Pharmacogenomics

Christian Kieling; Júlia P Genro; Mara H Hutz; Luis Augusto Rohde

Disclosures

Pharmacogenomics. 2010;11(3):407-419. 

In This Article

Abstract and Introduction

Abstract

Pharmacological treatment for attention deficit hyperactivity disorder, although highly effective, presents a marked variability in clinical response, optimal dosage needed and tolerability. Clinical and neurobiological investigations have juxtaposed findings on both response to medication and etiologic factors, generating the hypothesis that genetic factors may underlie differences in treatment outcome. Over the last decade, research has focused on the catecholaminergic system to investigate a potential role of genotype on pharmacological effect. Despite an increasing number of associations reported (for methylphenidate, nine in 2005, 24 in 2008 and 52 reported in the current article), the identification of clinically relevant genetic predictors of treatment response remains a challenge. At present, additional studies are required to allow for a shift from a trial-and-error approach to a more rational pharmacologic regimen that takes into account the likelihood of treatment effectiveness at the individual level.

Introduction

Attention deficit hyperactivity disorder (ADHD) is one of the most extensively investigated psychiatric disorders of childhood and adolescence.[1] Notwithstanding the remarkably well-replicated findings in the efficacy of pharmacological treatment, predictors of treatment response and side effects remain largely underspecified. In recent decades, clinical and neurobiological investigations have juxtaposed findings on both treatment response and etiologic factors.[2] The observation of a marked variability in treatment response, optimal dosage needed and tolerability has generated the hypothesis that genetic factors may underlie such differences. Evidence demonstrating the efficacy of pharmacological treatment with methylphenidate (MPH) has driven basic research to focus on the catecholaminergic system to uncover the genetic underpinnings of ADHD.

In recent decades, pharmacology and genetics have converged into models that investigate the role of genotype in predicting individual treatment response. Thus far, however, results of pharmacogenetic studies of ADHD have been variable, with conflicting results among small association studies.[3] This article presents an update, focusing on the published data of the pharmacogenetics of ADHD. We employed the same search strategy used by Polanczyk et al.[4] Remarkably, a comparison of pharmacogenetics of ADHD evidences a striking increase in the number of published articles (Figure 1). Here, we provide an updated review of the literature, presenting available results for each studied gene and providing some recommendations for future research on ADHD pharmacogenomics.

Figure 1.

Number of pharmacogenetic associations included in three reviews on methylphenidate response among individuals with attention deficit hyperactivity disorder.
ADRA2A: α-2A-adrenergic receptor gene; COMT: Catechol-O-methyl-transferase; DAT1/SLC6A3: Dopamine transporter; DRD4: Dopamine D4 receptor gene.
Data taken from [3,4].

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