Measurement Methods of BDNF Levels in Major Depression: A Qualitative Systematic Review of Clinical Trials

Abstract

There is evidence that the brain-derived neurotrophic factor (BDNF) has implications for the pathophysiology of major depressive disorders (MDD). Measures of BDNF levels are highly dependent on the methodologies used and these vary among different studies. Therefore, the aim of this study was to carry out a descriptive analysis of the methodologies used to measure BDNF in clinical trials (CT) in patients with the diagnosis of major depression. We conducted a qualitative systematic review of CT that included samples of subjects diagnosed with major depression and evaluated the BDNF levels as an outcome. The search was performed on Pubmed, Scielo, Psychinfo and Lilacs. The selected articles were analyzed according to the CONSORT Statement and their methods of BDNF collection and analysis were described. Twenty-eight studies were included in the final analysis. Of those, 6 trials (21.4%) involved non-pharmacological interventions and only half had the MDD diagnosis based on structured interview. Trials used different methods to evaluate BDNF levels: most of them verified serum BDNF levels, 17 (60.7%) trials mentioned that measured BDNF levels in duplicate and 9 (32.1%) collected blood in fasting. A variety of methods for BDNF collection and analysis was used in the different studies, making it difficult to compare results. However, despite of the methodology, BDNF seems to increase after treatment for major depression.

Development of mature BDNF‐specific sandwich ELISA

“…However, Promega BDNF ELISA kit has been used widely by researchers (Teche et al . ). Therefore, it is likely we used a faulty kit in this study.…”

“…However, current ELISA techniques utilized in many major studies that measure BDNF levels are performed with commercially available kits which cannot distinguish proBDNF from mBDNF (Teche et al . ). More recently, a BDNF ELISA kit from Adipo Bioscience (changed to Aviscera Bioscience, Santa Clara, CA, USA) (Yoshida et al .…”

“…As mBDNF and proBDNF show such different biological activities, there is growing importance in being able to distinguish and measure their levels accordingly (Hashimoto 2010;Teche et al 2013). BDNF ELISA was initially developed in 1990s based on two polyclonal antibodies for sandwich ELISA (Nawa et al 1995) or one-site ELISA using single monoclonal antibody (Kolbeck et al 1999).…”

Lower levels of brain‐derived neurotrophic factor are associated with melancholic psychomotor retardation among depressed inpatients

“…One of the most studied neurobiological changes in MDD, for example, is changes in neurotrophins, which are responsible for axon targeting, neuron growth, maturation of synapses, and synaptic plasticity . Brain‐derived neurotrophic factor (BDNF) is the best characterized neurotrophin in MDD, with several studies including meta‐analyses showing lower serum and plasma levels in depressed patients than in controls . Furthermore, hippocampal BDNF seems to be decreased by stress and increased by antidepressant treatment …”

“…33 Brain-derived neurotrophic factor (BDNF) is the best characterized neurotrophin in MDD, with several studies including meta-analyses showing lower serum and plasma levels in depressed patients than in controls. 34,35 Furthermore, hippocampal BDNF seems to be decreased by stress and increased by antidepressant treatment. 33,36 However, few studies have tested the correlation between melancholic features and BDNF.…”