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

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.

Peripheral S100B Protein Levels in Five Major Psychiatric Disorders: A Systematic Review

“…In the study by Navines et al (2022), patients with high baseline S100B levels significantly improved Montgomery Åsberg Depression Rating Scale scores compared to those with low S100B levels during pharmacotherapy with escitalopram or sertraline [ 79 ]. No correlation of S100B with ketamine treatment of drug-resistant depression was found [ 80 , 81 ], nor correlation with suicidal ideation in ketamine-treated patients [ 81 ].…”

Plasma Brain-Derived Neurotrophic Factor Levels in First-Episode and Recurrent Major Depression and before and after Bright Light Therapy in Treatment-Resistant Depression

“…In another study in TRD patients, plasma BDNF even decreased, primarily in ECT nonresponders [ 64 ]. An early change in plasma BDNF after a single ketamine infusion was positively correlated with clinical improvement after 1–2 weeks of multiple ketamine infusions [ 65 ], while one study reported no correlation between plasma BDNF and the achievement of response or remission following ECT in TRD patients [ 66 ]. Since the aforementioned studies [ 61 , 62 , 66 ] did not include a control group, it is unknown if those patients had a lower plasma BDNF concentration at baseline.…”