BDNF Val66Met and clinical response to antipsychotic drugs: A systematic review and meta-analysis

Abstract

Background: The polymorphic brain-derived neurotrophic factor (BDNF) gene has been postulated to be involved in inter-individual variability response to antipsychotic drugs.

Purpose: To perform a qualitative and quantitative synthesis of studies evaluating the influence of BDNF genetic variation on clinical response to antipsychotics.

Methods: The review protocol was published in the PROSPERO database (Reg. n(o) CRD42015024614). A comprehensive search was performed through PubMed, Web of Knowledge and Cochrane databases up to July 2015. The methodological quality of identified studies was assessed using the MINORS criteria. Publication bias was estimated and potential sources of heterogeneity were investigated via meta-regression, subgroup and sensitivity analyses.

Results: Nine studies including a total of 2461 antipsychotic-treated patients fulfilled inclusion criteria for meta-analysis of BDNF Val66Met. Using the random-effects model, the pooled results showed no significant association with antipsychotic response for the dominant (Met carriers vs Val/Val, OR: 0.93, 95% CI: 0.72-1.19, P=0.55), codominant (Met/Met vs Val/Val, OR: 0.82, 95% CI: 0.59-1.15, P=0.25), recessive (Met/Met vs Val carriers, OR: 0.81, 95% CI 0.60-1.10, P=0.18) or the allelic contrast (Met vs Val, OR: 0.92, 95% CI 0.76-1.10, P=0.34). Visual inspection of funnel plots and further evaluation with Egger's test did not suggest evidence of publication bias. Despite lack of significant heterogeneity in most comparisons, no evidence of association also emerged in the subgroup and sensitivity analyses conducted.

Conclusion: The present meta-analysis excludes a clinically relevant effect of BDNF Val66Met on antipsychotic drug response per se. Nevertheless, further investigation is still needed to clarify in well-designed, large sample-based studies, the impact of BDNF haplotypes containing the Val66Met polymorphism.

Keywords: Antipsychotics; Genetics; Meta-analysis; Schizophrenia and psychosis.