Bipolar disorder is characterized by severe mood symptoms including major depressive and manic episodes. Mania is a state of abnormally elevated mood and defining criteria for bipolar 1 disorder diagnosis. During manic episodes, many patients show cognitive dysfunction, contributing to reduced social function. Since the dopamine system is essential for normal cognitive performance, genes that regulate the dopamine system are of central interest for further investigations of cognitive function. COMT is involved in dopamine catabolism. In a number of studies, COMT has been associated with cognitive impairment in several psychiatric disorders, and also in the general population. In several independent studies, DAOA and COMT have been found to be associated with bipolar disorder. The DAOA gene acts through the NMDA receptors that have a central role in memory function and have been shown to be modified in bipolar disorder. The COMT and DAOA genes may contribute to the pathophysiology of psychiatric disorders, and especially cognitive manic symptoms, by the combined effect of dopaminergic and glutamatergic pathways. In a study, patients who had bipolar 1 disorder and certain DAOA, COMT genotypes, were found to have a slightly increased likelihood of having the most severe episodes of mania such as talkativeness, distractibility, and thought disorder. DAOA minor alleles rs3916967 C, rs2391191 A, and COMT rs5993883 T, were less common among the cognitive manic symptoms patients. The haplotype consisting of the three major DAO alleles TGA from SNPs rs3916967, rs2391191, and rs1935062, increased the risk for cognitive manic symptoms.