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

Abstract

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.

Is Brain-Derived Neurotrophic Factor (Bdnf) Val66met Polymorphism Associated With Obsessive-Compulsive Disorder? A Meta-Analysis

“…Previous studies have indicated that the Val66Met polymorphism of BDNF gene might play an important role in the pathophysiology of several psychotic disorders (Gattere et al 2018, Kirli et al 2018, Rybakowski 2008. The association between Val66Met and OCD susceptibility has been widely studied, although inconsistent results were obtained.…”

BDNF gene Val66Met polymorphisms as a predictor for clinical presentation in schizophrenia – recent findings

“…The primary diagnosis of participants encompasses schizophrenia and schizophrenia spectrum disorders, as well as other psychotic spectrum disorders as a subcategory for comparison – as in Karacetin ( 38 ). Kirli ( 29 ) studied individuals with psychotic experiences and psychotic disorders, including schizophrenia, to investigate longitudinal associations between the BDNF Val66Met polymorphism and different levels of the extended phenotype. Another study compared genotyping differences between healthy volunteers and unaffected first-degree relatives of patients with schizophrenia ( 26 ).…”

“…Most studies included a healthy control group, except those looking for associations between the BDNF Val66Met polymorphism and clinical facets of schizophrenia or the extended psychosis phenotype ( 29 , 36 ), or evaluating genetic implications in treatment resistance ( 30 ).…”