title: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Dipartimento di Scienze del Farmaco and Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica (CRIFF), Università del Piemonte Orientale "A. Avogadro", Largo Donegani 2, 28100 Novara, Italy.
authors: S
authors: S
authors: Cargnin
authors: Dipartimento di Scienze del Farmaco and Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica (CRIFF), Università del Piemonte Orientale "A. Avogadro", Largo Donegani 2, 28100 Novara, Italy.
authors: A
authors: A
authors: Massarotti
authors: Dipartimento di Scienze del Farmaco and Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica (CRIFF), Università del Piemonte Orientale "A. Avogadro", Largo Donegani 2, 28100 Novara, Italy. Electronic address: salvatore.terrazzino@uniupo.it.
authors: S
authors: S
authors: Terrazzino
mesh_terms: D014150:Antipsychotic Agents / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
chemical_list: D014150:Antipsychotic Agents; D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human
keywords: Antipsychotics; Genetics; Meta-analysis; Schizophrenia and psychosis