Plasma brain-derived neurotrophic factor (pBDNF) and executive dysfunctions in patients with major depressive disorder

Abstract

Objectives: Executive dysfunctions are frequently seen in patients with major depressive disorder (MDD) and normalise in many cases during effective antidepressant therapy. This study investigated whether a normalisation of executive dysfunctions during antidepressant treatment correlates with or can be predicted by clinical parameters or levels of brain-derived neurotrophic factor (BDNF).

Methods: In 110 MDD patients with executive dysfunctions (percentile <16), executive functions and plasma BDNF levels were analysed at baseline, and days 14 and 56 of an antidepressant treatment. BDNF exon IV and P11 methylation status was studied at baseline.

Results: Eighty patients (73%) experienced a normalisation of executive dysfunctions, while 30 (27%) suffered from persistent dysfunctions until day 56. Patients with persistent dysfunctions had significantly higher HAMD scores at days 14 and 56, and lower plasma BDNF levels at each time point than patients with a normalisation of dysfunctions (F₁= 10.18; P = 0.002). This was seen for verbal fluency, but not processing speed. BDNF exon IV and p11 promoter methylation was not associated with test performance.

Conclusions: Our results corroborate a concomitant amelioration of executive dysfunctions with successful antidepressant therapy and support a role of BDNF in the neural mechanisms underlying the normalisation of executive dysfunctions in MDD.

ClinicalTrials.gov number: NCT00974155; EudraCT: 2008-008280-96

Keywords:

• Major depressive disorder
• brain-derived neurotrophic factor
• executive function
• BDNF exon IV and p11 promoter methylation
• antidepressant therapy

Acknowledgements

The authors are grateful to the members of the EMC Study Group, who were involved in the acquisition of data for this additional scientific investigation. These members are: Univ.-Prof. Dr. Klaus Lieb, Dr. André Tadić, Univ.-Prof. Christoph Hiemke, Dr. Nadine Dreimüller, Dr. Ömür Baskaya, Dr. Danuta Krannich, Dr. Sonja Lorenz, Annette Bernius, Dr. Tillmann Weichert, Dr. Markus Lorscheider, Dr. Martin Klosz, Dr. Dipl.-Psych. Isabella Helmreich, Dipl.-Psych. Karen Grüllich, Elnaz Ostad Haji, Yvonne Lober, Danuta Weichert, Konrad Schlicht, Dr. Christina Weigert, Dr. Jana Maurer (Department of Psychiatry and Psychotherapy, University Medical Centre Mainz); Konstantin Mayer (Sana Klinikum Offenbach, 65346 Offenbach, Germany); Prof. Dr. Dieter F. Braus, Dr. Julia Reiff, Dr. Christoph Kindler, Dr. Svenja Davis, Dr. Claudia Ginap, Dipl.-Psych. Julia Kraus, Dipl.-Psych. Sabine Kaaden, Dr. Dipl.-Psych. Jelena Janzen, Dipl.-Psych. Nina Löffler, Caterina Topaloglu, Elitza Klutscher (Clinic for Psychiatry and Psychotherapy, Wiesbaden).

Statement of interest

PD Dr. André Tadic is designated as inventor of the European patent number 12171541.1–2404 ‘Method for predicting response or non-response to a mono-aminergic antidepressant’. Additionally, Dr. Tadic has received consultancy fees from Janssen and Novartis. Prof. Dr. Helge Frieling is designated as inventor of the European patent number 12171541.1–2404 ‘Method for predicting response or non-response to a mono-aminergic antidepressant’. Prof. Dr. Klaus Lieb is designated as inventor of the European patent number 12171541.1–2404 ‘Method for predicting response or non-response to a mono-aminergic antidepressant’. Prof. Dr. Dieter F. Braus has received in the last 5 years fees for unrestricted educational lectures from Lilly, Janssen, Bayer, Lundbeck, Servier, Shire, TAD Pharma.

None of the authors has relevant financial interests in this manuscript.

Additional information

Funding

The EMC trial was funded by the German Federal Ministry for Education and Research (BMBF grant no: 01 KG 0906; applicants: KL, AT, CH, ND, KK); the herein presented additional investigations are not part of the funding. The BMBF had no role in the conception of the study design, in the writing of the manuscript or the decision to submit the manuscript for publication. The assessment of neuropsychological functioning was funded by the German Research Foundation (“Deutsche Forschungsgemeinschaft, DFG” (funding number: WA 2970/1-1). The DFG had no role in the conception of the study design, in the writing of the manuscript or the decision to submit the manuscript for publication.