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Methylation of the promoter of brain-derived neurotrophic factor exon IV and antidepressant response in major depression

Molecular Psychiatry volume 19, pages 281–283 (2014)Cite this article

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Insufficient response to antidepressant pharmacotherapy with monoaminergic drugs is a major problem in the therapy of major depression (MD), occurring in up to two-thirds of depressed patients. To date, there is no biological marker reliably determining patients at high risk to treatment failure. Here, we report the first preliminary evidence that patients showing hypomethylation of the promoter region of the brain-derived neurotrophic factor (BDNF) gene are unlikely to benefit from antidepressant pharmacotherapy.

Several lines of evidence have linked the neurotrophin BDNF with both the pathophysiology of depression and the mode of action of antidepressants.1 Effective antidepressive treatment seems to increase peripheral BDNF levels.2, 3 We have shown earlier that the non-increase of BDNF in serum4 or plasma5 during the first week of antidepressant treatment predicts the final non-response and non-remission with high sensitivity, suggesting that early changes in peripheral BDNF may constitute or reflect a necessary prerequisite for final treatment response. For the complex regulation of BDNF expression by methylation of DNA and histone modifications, exon IV has a dominant role.6, 7 However, almost all evidence regarding these effects has been derived from animal studies. So far, clinical studies in the field showed that (i) methylation profiles of bdnf exon I can distinguish between depressed patients and healthy controls,8 and (ii) responders to treatment with antidepressants display a decrease in bdnf exon IV-related trimethylation at histone H3.9

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Acknowledgements

This work was supported by in-house research funds of the University Medical Centre Mainz and Hannover Medical School. Parts of the doctoral thesis of Konrad F. Schlicht are incorporated into this report.

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Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, University Medical Centre, Mainz, Germany

    A Tadić, K F Schlicht, N Dreimüller & K Lieb

  2. Department of Psychiatry, Molecular Neuroscience Laboratory, Socialpsychiatry and Psychotherapy, Hannover Medical School (MHH), Hanover, Germany

    L Müller-Engling, A Kotsiari, A Kleimann, S Bleich & H Frieling

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  1. A Tadić
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  2. L Müller-Engling
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Correspondence to A Tadić.

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Competing interests

AT, KL, SB and HF are designated as inventors of the European patent number 12171541.1–2404 ‘Method for predicting response or non-response to a monoaminergic antidepressant’.

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Tadić, A., Müller-Engling, L., Schlicht, K. et al. Methylation of the promoter of brain-derived neurotrophic factor exon IV and antidepressant response in major depression. Mol Psychiatry 19, 281–283 (2014). https://doi.org/10.1038/mp.2013.58

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