Antipsychotic medications and cognitive functioning in bipolar disorder: moderating effects of COMT Val(108/158) Met genotype

Background: There is a negative association between the use of antipsychotics and cognitive functioning in bipolar patients, which may be mediated by altered dopamine signaling in selected brain areas, and moderation thereof by genetic sequence variation such as COMT Val(108/158)Met. The interaction between antipsychotic drug use and the COMT Val(108/158)Met genotype on two-year cognitive functioning in bipolar patients was examined. Methods: Interaction between the COMT Val(108/158)Met and antipsychotics on a composite cognitive measure was examined in 51 bipolar patients who were assessed 12 times at two-monthly intervals over a period of two years (379 observations). Results: There was a significant negative effect of the interaction between antipsychotic medications and Val allele load on the composite cognitive measure in bipolar patients (p <0.001). Conclusions: The negative effects of antipsychotics on cognitive functioning in bipolar disorder may be moderated by the COMT Val (108/158) Met genotype, with a negative effect of Val allele load. If replicated, the results may be indicative of pharmacogenetic interactions in bipolar disorder.