BDNF Val66Met and spontaneous dyskinesias in non-clinical psychosis

Background: Evidence indicating that symptoms of non-clinical psychosis (NCP) occur in 6-8% of the general population suggests that psychosis may occur across a continuum. Although a number of studies have examined environmental contributors, to date there have been few investigations of biological/genetic factors in this integral population. A recent study observed spontaneous dyskinetic movements (reflecting an innervated striatal system) in individuals reporting NCP. The present investigation is designed to replicate this finding and determine if brain-derived neurotrophic factor (BDNF) (implicated in striatal dopamine function) is associated with dyskinesias. Method: A total of 68 young-adult participants reporting High and Low-NCP were assessed for dyskinetic movements using a sensitive instrumental measure of force variability. Saliva from the participants was genotyped for val66met (rs6265), a common functional polymorphism of the BDNF gene (the Met allele is associated with lower activity-dependent release of BDNF). Results: Participants in the High-NCP group showed significantly elevated levels of force variability. Met allele carriers exhibited significantly higher levels of force variability when compared with the Val homozygotes. Logistic regression indicated that the odds of membership in the High-NCP group were significantly higher given the presence of dyskinesias (OR. =. 2.32; CI: 1.25-4.28). Conclusion: Findings of elevated force variability suggest that individuals with NCP exhibit subtle signs of striatal vulnerability, reflected more dramatically as jerking and hyperkinetic movements in patients with formal psychosis. The results are consistent with a larger literature implicating BDNF as a critical factor underlying abnormal movements, and suggest that specific candidate genes underlie putative markers across a psychosis continuum.