Association between catechol-O-methyltransferase Val(108/158)Met polymorphism and psychotic features of bipolar...

Catechol-O-methyltransferase (COMT) inactivates catecholamines, and a G-A transition in the COMT gene (rs4680) influences the enzyme activity and the interaction between cortical and subcortical dopaminergic neurotransmission. Studies in healthy participants and in patients affected by schizophrenia suggested that rs4680 can influence the propensity to develop psychotic symptoms, with the Met low-activity allele exerting a protective role. Previous studies in bipolar patients reported non-significant trends in the same direction.

We genotyped rs4680 in a sample of 467 patients affected by bipolar disorder type I with or without a previous illness episode with psychotic features (DSM-IV criteria: delusions or hallucinations).

We observed a significant association between homozygosis for the rs4680 COMT low-activity variant and a reduced risk of experiencing illness episodes with psychotic features during the course of the illness. The Met/Met genotype was more common among patients without psychotic features, and while in the non-psychotic group the Val/Val genotype had a distribution similar to Met/Met, in the group of patients who experienced episodes with psychotic symptoms the proportion of Val/Val homozygotes was the double of Met/Met.

We suggest that rs4680 could be an inheritable aspect of the mechanisms of dopamine regulation that could influence the individual susceptibility of patients with bipolar disorder to develop psychotic symptoms.