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

Published online by Cambridge University Press:  23 March 2020

S. Cargnin ,
A. Massarotti  and
S. Terrazzino
S. Cargnin
Affiliation:
Dipartimento di Scienze del Farmaco and Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica (CRIFF), Università del Piemonte Orientale “A. Avogadro”, Largo Donegani 2, 28100Novara, Italy
A. Massarotti
Affiliation:
Dipartimento di Scienze del Farmaco and Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica (CRIFF), Università del Piemonte Orientale “A. Avogadro”, Largo Donegani 2, 28100Novara, Italy
S. Terrazzino*
Affiliation:
Dipartimento di Scienze del Farmaco and Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica (CRIFF), Università del Piemonte Orientale “A. Avogadro”, Largo Donegani 2, 28100Novara, Italy
*
⁎ Corresponding author. Tel.: +39 3 213 758 27; fax: +39 3 213 758 21. E-mail address:salvatore.terrazzino@uniupo.it (S. Terrazzino).
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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. no 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

Schizophrenia and psychosisGeneticsAntipsychoticsMeta-analysisBDNF brain-derived neurotrophic factorBPRS Brief Psychiatric Rating ScaleCGI Clinical Global Impression ScaleGAS Global Assessment ScaleHWE Hardy–Weinberg EquilibriumMAF minor allele frequencyPANNS Positive and Negative Syndrome ScaleOR odds ratioSAD schizoaffective disorderSCZ schizophrenia
Type
Review
Information
European Psychiatry , Volume 33 , Issue 1 , March 2016 , pp. 45 - 53
Copyright
Copyright © European Psychiatric Association 2016

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