Jiang Haitang, Veldman Emma R, Tiger Mikael, Ekman Carl-Johan, Lundberg Johan, Svenningsson Per
Department of Psychosomatics and Psychiatry, Zhongda Hospital, Medical School of Southeast University, Nanjing, China.
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Front Neurosci. 2021 Jul 20;15:698633. doi: 10.3389/fnins.2021.698633. eCollection 2021.
Evidence 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.
We 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 ( = 20) to a placebo ( = 10) control (saline). Severity of depression was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS).
Plasma 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, = 0.031), though this change did not survive correction for multiple comparisons.
These 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.
有证据表明，脑源性神经营养因子（BDNF）和S100钙结合蛋白B（S100B）在重度抑郁症（MDD）的发病机制中起关键作用，并且它们被认为是抗抑郁反应的预测指标。氯胺酮在MDD中具有快速抗抑郁作用，临床前研究表明，氯胺酮的抗抑郁作用需要提高BDNF水平。然而，观察氯胺酮干预后血BDNF水平变化的研究结果并不一致，且缺乏关于血浆S100B在MDD患者氯胺酮治疗中作用的研究。
我们评估了30例对选择性5-羟色胺再摄取抑制剂（SSRI）耐药的MDD患者血浆中成熟BDNF（mBDNF）、S100B水平，以及它们与抑郁严重程度的相关性。这些患者参与了一项氯胺酮随机对照试验，将其与安慰剂（n = 10）对照组（生理盐水）进行比较（n = 20）。使用蒙哥马利-Åsberg抑郁评定量表（MADRS）评估抑郁严重程度。
与安慰剂相比，单次注射氯胺酮1 - 2天后，血浆mBDNF和S100B无显著变化。氯胺酮治疗的反应者与无反应者相比，血浆mBDNF和S100B水平无显著差异。在开放标签的氯胺酮治疗1 - 2周后，血浆mBDNF水平的变化与MADRS评分的改善呈正相关（rho = 0.495，p = 0.031），尽管这种变化在多重比较校正后未存活。
这些发现不支持氯胺酮治疗会增加MDD患者血浆BDNF水平的假设。未观察到氯胺酮治疗对血浆S100B水平有影响。
