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High baseline BDNF serum levels and early psychopathological improvement are predictive of treatment outcome in major depression

Psychopharmacology volume 231, pages 2955–2965 (2014)Cite this article

Abstract

Rationale

Major depressive disorder has been associated with low serum levels of brain-derived neurotrophic factor (sBDNF), which is functionally involved in neuroplasticity. Although sBDNF levels tend to normalize following psychopathological improvement with antidepressant treatment, it is unclear how closely sBDNF changes are associated with treatment outcome.

Objectives

To examine whether baseline sBDNF or early changes in sBDNF are predictive of response to therapy.

Methods

Twenty-five patients with major depressive disorder underwent standardized treatment with duloxetine. Severity of depression, measured by the Hamilton Depression Rating Scale, and sBDNF were assessed at baseline, and after 1, 2, and 6 weeks of treatment. Therapy outcome after 6 weeks was defined as response (≥50 % reduction in baseline Hamilton Depression Rating score) and remission (Hamilton Depression Rating score <8). The predictive values for treatment outcome of baseline sBDNF, and early (i.e., ≤2 weeks) changes in sBDNF and Hamilton Depression Rating score were also assessed.

Results

At baseline, sBDNF correlated with Hamilton Depression Rating scores. Treatment response was associated with a higher baseline sBDNF concentration, and a greater Hamilton Depression Rating score reduction after 1 and 2 weeks. A greater early rise in sBDNF correlated with a decreased early Hamilton Depression Rating score reduction.

Conclusions

Even though higher baseline sBDNF levels are associated with more severe depression, they may reflect an increased capacity to respond to treatment. In contrast, changes in sBDNF over the full course of treatment are not associated with psychopathological improvement.

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Fig. 1

Notes

  1. Nevertheless, inpatients did not differ from outpatients concerning values of sBDNF levels and HDRS scores at later timepoints and changes of HDRS scores or sBDNF levels between any timepoint and baseline were not significantly different between setting groups.

  2. Accordingly, when HDRS score was declining over course of treatment, the value of HDRS-Wxdelta was negative.

  3. After including all initially recruited patients (n = 31) into the analysis, correlation between baseline values of sBDNF and HDRS was similar (r = 0.463; p = 0.010).

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Acknowledgments

This study is an Investigator Initiated Study (ITT) financed by a special grant from Eli Lilly SA, Switzerland. The company had, however, no influence on either the designing or writing of the protocol of the study or analysis and interpretation of study results. The preparation of the manuscript for publication was not supported by the company. E. H. and A. D. are members of the Eli Lilly Advisory Board. A. D. has consulted for the company on various occasions and was involved in the preparation of paid expert reports and educational programs for GPs. No potential conflicts of interests exist for other authors. The authors thank Nick Emler (Surrey, UK) for proofreading the manuscript.

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Affiliations

  1. Center for Affective, Stress and Sleep Disorders (ZASS), Psychiatric Clinics of the University of Basel, Wilhelm Klein-Strasse 27, 4012, Basel, Switzerland

    Thorsten Mikoteit, Johannes Beck, Serge Brand & Edith Holsboer-Trachsler

  2. Neurobiology Laboratory for Brain Aging and Mental Health, Psychiatric Clinics of the University of Basel, Basel, Switzerland

    Anne Eckert

  3. Center of Education and Research (COEUR), Psychiatric Service Canton of St. Gallen, Wil, St. Gallen, Switzerland

    Ulrich Hemmeter

  4. ADI International Institute for Advancement of Drug Development GmbH, Basel, Switzerland

    Roland Bischof & Alexandra Delini-Stula

Authors
  1. Thorsten Mikoteit
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  2. Johannes Beck
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  3. Anne Eckert
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  4. Ulrich Hemmeter
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Correspondence to Thorsten Mikoteit.

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Thorsten Mikoteit and Johannes Beck contributed to this paper equally

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Mikoteit, T., Beck, J., Eckert, A. et al. High baseline BDNF serum levels and early psychopathological improvement are predictive of treatment outcome in major depression. Psychopharmacology 231, 2955–2965 (2014). https://doi.org/10.1007/s00213-014-3475-8

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  • DOI: https://doi.org/10.1007/s00213-014-3475-8

Keywords

  • Brain-derived neurotrophic factor (BDNF)
  • Serum
  • Depression
  • Treatment outcome
  • Early response
  • Response
  • Remission
  • Antidepressants
  • Serotonin norepinephrine reuptake inhibitor (SNRI)
  • Duloxetine