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BDNF Val66Met polymorphism and clinical response to antipsychotic treatment in schizophrenia and schizoaffective disorder patients: a meta-analysis

The Pharmacogenomics Journal volume 19, pages 269–276 (2019)Cite this article

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Abstract

Brain-derived neurotrophic factor (BDNF) plays an important role in dopaminergic and serotonergic neurotransmission by modulating dopaminergic neuron differentiation and establishment. Multiple studies have analyzed the functional BDNF Val66Met variant in relation to antipsychotic response in schizophrenia (SCZ) patients, yielding mixed results. A meta-analysis was thus performed to examine the relationship between this variant and symptom improvement during antipsychotic treatment. Searches using PubMed, Web of Science, and PsycInfo until October 2017 yielded 11 studies that met inclusion criteria (total n = 3774). These studies investigated the BDNF Val66Met variant and antipsychotic response in patients with SCZ or schizoaffective disorder. Responders to antipsychotics were defined using the original criteria applied in each study. Effect sizes were computed using odds ratios, which were pooled according to the Mantel–Haenszel method. The BDNF Val66Met variant was not associated with the total number of responders and non-responders (p > 0.05) under dominant, recessive, or allelic models. Secondary analyses stratifying for individuals of each ethnicity and drug type also revealed no significant associations. Our findings suggest that the BDNF Val66Met variant is not associated with response to antipsychotics in individuals with SCZ. However, considering the current sample size, small effects cannot be ruled out. Moreover, recent studies have suggested that Val66Met forms haplotypes with other BDNF variants. Future studies should examine the Val66Met variant in conjunction with these other variants in relation to antipsychotic response. Moreover, since illness duration appears to influence BDNF levels in SCZ patients, future studies should aim to control for this potential confounding factor in response analyses.

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Acknowledgements

The principal investigators of the CATIE trial were Jeffrey A Lieberman, MD, T Scott Stroup, MD, MPH, and Joseph P McEvoy, MD. The CATIE trial was supported by a grant from the National Institute of Mental Health (N01 MH900001) and MH074027 (PI Patrick F Sullivan). Genotyping was funded by Eli Lilly and Company. CCZ is supported by the Brain and Behavior Research Foundation, American Foundation for Suicide Prevention, and Eli Lilly. EH is supported by the Canada Graduate Scholarship (CGS). JLK is supported by the CIHR grant “Strategies for gene discovery in schizophrenia: subphenotypes, deep sequencing and interaction”. GZ is supported by a CIHR postdoctoral fellowship. The remaining authors do not have any research support to disclose. The authors would like to acknowledge the contributions of DJM (Dr. Daniel J. Mueller) for his support. The authors have no further acknowledgements.

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This work did not receive any direct funding support.

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Author notes

  1. These authors contributed equally: Eric Huang, Nuwan C. Hettige

Authors and Affiliations

  1. Psychiatric Neurogenetics Section, Campbell Family Research Institute Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada

    Eric Huang, Nuwan C. Hettige, Gwyneth Zai, Julia Tomasi, Justin Huang, Clement C. Zai, Arun K. Tiwari & James L. Kennedy

  2. Institute of Medical Science, University of Toronto, Toronto, ON, Canada

    Eric Huang, Nuwan C. Hettige & Julia Tomasi

  3. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    Gwyneth Zai, Clement C. Zai, Arun K. Tiwari & James L. Kennedy

  4. Frederick W. Thompson Anxiety Disorders Centre, Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Gwyneth Zai

  5. Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia

    Nela Pivac & Matea Nikolac Perkovic

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Correspondence to James L. Kennedy.

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Conflict of interest

JLK has acted as a consultant or received honoraria from GlaxoSmith-Kline, Sanofi-Aventis, Dainippon-Sumitomo, Novartis, Shire, Eli Lilly, and Roche; he is on a Scientific Advisory Board member (unpaid) of AssureRx Health Inc. The remaining authors have no potential conflicts of interests to disclose.

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Huang, E., Hettige, N.C., Zai, G. et al. BDNF Val66Met polymorphism and clinical response to antipsychotic treatment in schizophrenia and schizoaffective disorder patients: a meta-analysis. Pharmacogenomics J 19, 269–276 (2019). https://doi.org/10.1038/s41397-018-0041-5

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