In conclusion, the COMT Val(158)Met polymorphism may constitute a genetic risk factor for psychotic symptoms in the context of combined exposure to childhood maltreatment and cannabis use.
Further examination of this interaction revealed that in patients with the MTHFR 677 T-allele, COMT Met/Met individuals displayed the largest increases in psychotic symptoms in reaction to ESM stress [χ(2)(2) = 29.51; P < 0.0001], whereas in patients with the MTHFR 677 C/C genotype no significant COMT Val158Met × ESM stress interaction was apparent [χ(2)(2) = 3.65; P = 0.16].
In patients affected by bipolar disorder rs4680 can influence antidepressant response and the propensity to develop psychotic symptoms, with the Met/Met genotype exerting a protective role.
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.
The findings suggest that the COMT(Val158Met) polymorphism moderates affective and psychotic responses to stress in patients with psychosis, providing evidence for gene-environment interaction mechanisms in the formation of psychotic symptoms.