A second look: No effect of the COMT Val158Met polymorphism on conflict adaptation in youth with chromosome 22q11.2 deletion syndrome

The catechol o-methyltransferase gene (COMT) gene is located at chromosome 22q11.2, where the most common human genetic microdeletion occurs. The resultant syndrome (22q11.2DS) confers both a high risk of psychotic disorder (~25 fold) and schizophrenia-related executive dysfunction (e.g. Murphy et al., 1999). Therefore, 22q11.2DS has been a model population in which to study COMT behavioral phenotypes, specifically executive function and clinical psychosis (e.g. Tunbridge et al., 2004). However, in 22q11.2DS, neither allele of the codominant, functional COMT Val108/158Met polymorphism (rs4680) has been reliably associated with clinical psychosis (Murphy et al., 1999; Gothelf et al., 2005; Bassett et al., 2007; Boot et al., 2011) or executive function (Bearden et al., 2004; Glaser et al., 2006; Shashi et al., 2010). We have previously reported an association between the rs4680 Met allele and conflict adaptation (Takarae et al., 2009) but not to flanker interference (Stoddard et al., 2011) within the same task. To resolve this discrepancy, we re-examined the association between rs4860 and impairment in conflict adaptation in the larger sample (Stoddard et al., 2011) using the same method as before (Takarae et al., 2009).