Plasma Levels of Brain-Derived Neurotrophic Factor and S100B in Relation to Antidepressant Response to Ketamine.

Haitang Jiang,Carl-Johan Ekman,Per Svenningsson,Mikael Tiger,Johan Lundberg,Emma R. Veldman

doi:10.3389/fnins.2021.698633

Abstract

BackgroundEvidence demonstrates that brain-derived neurotrophic factor (BDNF) and S100 calcium-binding protein B (S100B) have a pivotal role in the pathogenesis of major depressive disorder (MDD) and they are proposed as predictors of antidepressant response. Ketamine produces rapid antidepressant effects in MDD and pre-clinical studies suggest the necessity of increased BDNF levels for the antidepressant action of ketamine. However, studies observing the change of blood BDNF levels after ketamine intervention are inconsistent and studies about the role of plasma S100B in ketamine administration in MDD patients are lacking.MethodWe evaluated mature BDNF (mBDNF), S100B levels in plasma and their associations with depression severity in 30 Selective Serotonin Reuptake Inhibitor (SSRI)-resistant MDD patients enrolled in a randomized controlled trial of ketamine compared (n = 20) to a placebo (n = 10) control (saline). Severity of depression was assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS).ResultsPlasma mBDNF and S100B were not significantly changed after 1–2 days of single ketamine compared to placebo. Plasma mBDNF and S100B levels did not significantly differ in responders compared to non-responders of ketamine treatment. The change of plasma mBDNF levels was positively correlated with the improvement of MADRS score after 1–2 weeks of open-label ketamine treatment (rho = 0.495, p = 0.031), though this change did not survive correction for multiple comparisons.ConclusionThese findings do not support the hypothesis that ketamine treatment increases BDNF plasma levels in MDD patients. No effect of ketamine treatment on S100B plasma levels was seen.

Highlights

Major depressive disorder (MDD) is the most common psychiatric disorder, affecting more than 300 million people, and the major cause of disability and suicidal death globally (World Health Organization, 2017)
We examined the relationship between plasma levels of mature BDNF (mBDNF) and S100 calcium-binding protein B (S100B) and depression severity, obtained during a randomized, placebo-controlled trial of ketamine in Selective Serotonin Reuptake Inhibitor (SSRI)-resistant MDD
Plasma mBDNF and S100B levels did not significantly change in responders to ketamine treatment (n = 15; brain-derived neurotrophic factor (BDNF): p = 0.950; S100B: p = 0.503), nor did post ketamine protein levels differ between responders and non-responders (n = 5) when corrected for baseline levels, age and gender (BDNF: p = 0.563; S100B: p = 0.832)

Summary

Introduction

Major depressive disorder (MDD) is the most common psychiatric disorder, affecting more than 300 million people, and the major cause of disability and suicidal death globally (World Health Organization, 2017). MDD patients with a BDNF Val66Met allele are less likely to respond to ketamine (Laje et al, 2012). These findings suggest that increased BDNF levels are required for the antidepressant actions of ketamine. While increased plasma BDNF levels after ketamine intervention in MDD patients have been repeatedly reported (Duncan et al, 2013; Haile et al, 2014), other studies point toward a lack of effect (Machado-Vieira et al, 2009; Medeiros et al, 2021). Ketamine produces rapid antidepressant effects in MDD and pre-clinical studies suggest the necessity of increased BDNF levels for the antidepressant action of ketamine. Studies observing the change of blood BDNF levels after ketamine intervention are inconsistent and studies about the role of plasma S100B in ketamine administration in MDD patients are lacking

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