Is BDNF-Val66Met polymorphism associated with psychotic experiences and psychotic disorder outcome? Evidence from a 6 years prospective population-based cohort study

There is little research on genetic risk for the extended psychosis phenotype ranging from psychotic experiences (PEs) to psychotic disorders (PDs). In this general population-based prospective cohort study, the longitudinal associations between BDNF-Val66Met polymorphism and the different levels of the extended psychosis phenotype were investigated. Addresses were contacted in a multistage clustered probability sampling frame covering 11 districts and 302 neighborhoods at baseline (n = 4011). A nested case-control study (n = 366) recruited individuals with PEs and PDs as well as individuals with no psychotic symptoms. In this subgroup, blood sampling for genetic analysis and assessment of environmental exposures were carried out, followed by clinical re-appraisal at follow-up 6 years later (n = 254). The BDNF-Val66Met polymorphism was significantly associated with the extended psychosis phenotype. The pattern of the association was that the BDNF-Val66Met polymorphism impacted in a dose-response but extra-linear fashion, with stronger impact at the PD end of the extended psychosis phenotype. Associations were still significant after adjusting for sociodemographic factors and environmental exposures including life events, childhood adversity, socioeconomic status, urbanicity, and cannabis use. The BDNF-Val66Met polymorphism may index susceptibility to expression of psychosis along a spectrum.