Various enzymes involved in the synthesis and breakdown of neurotransmitters have also been analyzed for associations with acute response to stimulant drugs. One major candidate gene is catechol O-methyl transferase (COMT). This gene codes for an enzyme that preferentially metabolizes dopamine in the prefrontal cortex, rather than in the limbic and striatal brain regions, where the dopamine transporter is more important for clearance (Chen et al. 2004b). COMT contains a val→met coding polymorphism (val158-met; rs4680; G(val)/A(met)) that has been associated with a variety of phenotypes including personality, cognition, risk for psychiatric disorders (Tunbridge et al. 2006), and pain sensitivity (Andersen and Skorpen 2009). The met allele has been associated with 3–4 times lower activity compared to the val allele (Lachman et al. 1996).
