COMT and bipolar I disorder: Fryar-Williams (2016) discussed the impact of MTHFR deficiency on deficits in the methylation cycle related to the etiology of psychosis. Rahimi et al. (2016) have identified a synergistic interaction between the VAL allele of COMT and the T allele of the MTHFR 677CT polymorphism, which increased the incidence of Bipolar I disorder by a factor of 2.58 (p < 003). On the other hand, Wang et al. (2015) found that the VAL/VAL genotype of COMT in combination with the MTHFR 677TT genotype had a protective effect on the development of Bipolar II disorder among Han Chinese.