Previous studies of DRD1 variants and ADHD have been inconsistent. For example, at least two studies indicated no association between rs4532 and ADHD (Kirley, Hawi, Daly, McCarron, Mullins, Millar, Waldman, Fitzgerald & Gill, 2002; Nyman, Ogdie, Loukola, Varilo, Taanila, Hurtig, Moilanen, Loo, McGough, Jarvelin, Smalley, Nelson & Peltonen, 2007), whereas others reported (Misener, Luca, Azeke, Crosbie, Waldman, Tannock, Roberts, Malone, Schachar, Ickowicz, Kennedy & Barr, 2004) and replicated (Luca, Laurin, Misener, Wigg, Anderson, Cate-Carter, Tannock, Humphries, Lovett & Barr, 2007) a significant association between the minor rs4532/C allele and inattention. The rs4532/C allele has also been associated with several ADHD-related traits including impulsive response/reaction time (Bobb, Addington, Sidransky, Gornick, Lerch, Greenstein, Clasen, Sharp, Inoff-Germain, Wavrant-De Vrièze, Arcos-Burgos, Straub, Hardy, Castellanos & Rapoport, 2005) and nicotine dependence (Huang et al., 2008; McClernon & Kollins, 2008). In the current study, rs4532/C, which is associated with a decrease in D1 expression, decoupled the relationship between improvements in working memory manipulation and the remission of ADHD symptoms during development. We speculate that lower D1 expression might hinder cognitive development in ADHD in a way that leads to a generalized, behaviorally dysregulated phenotype that is difficult to reliably predict from traditional measurement tools.
