The serotonin transporter has also been investigated for its role in sub-chronic methylphenidate treatment response in children diagnosed with ADHD (Thakur et al. 2010). In a 2 week trial, children received placebo and methylphenidate at varying doses. Subjects homozygous for the higher expressing LA had the worst response to placebo but the best response to methylphenidate, heterozygotes were intermediate, and individuals homozygous for the LS and LG alleles exhibited the best response to placebo but deterioration with methylphenidate treatment as measured by the CGI-Parents subscale. Thus, lower expression of SLC6A4 is associated with stronger euphoric, but weaker therapeutic responses to stimulant drugs.
