Age of onset and duration of untreated psychosis in first episode psychosis: Interaction effects between cannabis and comt

Abstract

Introduction: Age of onset and duration of untreated Psychosis (DUP) have been proposed as key factors in the prognosis of psychosis. Whereas gender differences in age of onset have been established and there is an emerging evidence of the association between cannabis use and an earlier age of onset, the role of other variables remains unclear. The Val158Met polymorphism of Catechol-O-Methyltransferase (COMT) has shown differences in clinical variables between genotypes and a possible association with an earlier age of onset. Additionally, an interaction between COMT genotype and cannabis has been previously found in the modulation of risk of psychosis. The aim of this study was to examine the effects of COMT genotype, cannabis and their interaction in the age of onset and DUP in a representative group of first episode psychosis patients. Methods: Aged of onset, DUP and cannabis consumption (regular user vs. sporadic or non-user) were assessed in 169 caucasian drug-naïve patients with a first-episode of non-affective psychosis. COMT polymorphism was typed using PCR of the relevant region followed by digestion with NlaIII and electrophoresis. A multivariate ANCOVA was performed with DUP and Age of onset as dependent variables, cannabis and COMT genotype as fixed factors and gender as a covariate. Results: The MANCOVA was significant for age of onset and DUP. Cannabis users had a significant earlier age of onset (F=16.887; p<0.001). Age of onset was later in the Met homozygote group (non significant, F=2.348; p=0.099). The cannabis-COMT interaction showed a significant effect in both DUP and age of onset (F=3.816; p=0.024). Post hoc analyses showed that differences between genotypes were only present in the non-cannabis users group. Conclusions: Cannabis users had an earlier age of onset and shorter DUPs. Val carriers had an earlier age of onset and longer DUPs, but only in the non-cannabis user group. Cannabis seems to modulate the age of onset and DUP in first episode psychosis independently of gender and to moderate the effect of COMT Val158Met polymorphism.