短期大剂量益生菌补充对抑郁症患者认知、相关脑功能和脑源性神经营养因子的影响：一项随机对照试验的二次分析。
Effect of short-term, high-dose probiotic supplementation on cognition, related brain functions and BDNF in patients with depression: a secondary analysis of a randomized controlled trial.
机构信息
From the University of Basel, Department of Psychiatry (UPK), Basel, Switzerland (Schneider, Doll, Schweinfurth, Kettelhack, Schaub, Yamanbaeva, Varghese, Mählmann, Brand, Eckert, Borgwardt, Lang, Schmidt); the Transfaculty Research Platform Molecular and Cognitive Neuroscience, University of Basel, Basel, Switzerland (Varghese, Eckert); the Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran (Brand); the Substance Abuse Prevention Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran (Brand); the Department of Sport, Exercise and Health, Division of Sport Science and Psychosocial Health, University of Basel, Basel, Switzerland (Brand); the School of Medicine, Tehran University of Medical Sciences, Tehran, Iran (Brand); the Department of Research, St. Clara Hospital, Basel, Switzerland ([CE; authors were not indicated for this affiliation]}; the Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany (Borgwardt).
From the University of Basel, Department of Psychiatry (UPK), Basel, Switzerland (Schneider, Doll, Schweinfurth, Kettelhack, Schaub, Yamanbaeva, Varghese, Mählmann, Brand, Eckert, Borgwardt, Lang, Schmidt); the Transfaculty Research Platform Molecular and Cognitive Neuroscience, University of Basel, Basel, Switzerland (Varghese, Eckert); the Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran (Brand); the Substance Abuse Prevention Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran (Brand); the Department of Sport, Exercise and Health, Division of Sport Science and Psychosocial Health, University of Basel, Basel, Switzerland (Brand); the School of Medicine, Tehran University of Medical Sciences, Tehran, Iran (Brand); the Department of Research, St. Clara Hospital, Basel, Switzerland ([CE; authors were not indicated for this affiliation]}; the Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany (Borgwardt)
出版信息
J Psychiatry Neurosci. 2023 Jan 18;48(1):E23-E33. doi: 10.1503/jpn.220117. Print 2023 Jan-Feb.
BACKGROUND
In major depressive disorder (MDD), cognitive dysfunctions strongly contribute to functional impairments but are barely addressed in current therapies. Novel treatment strategies addressing cognitive symptoms in depression are needed. As the gut microbiota-brain axis is linked to depression and cognition, we investigated the effect of a 4-week high-dose probiotic supplementation on cognitive symptoms in depression.
METHODS
This randomized controlled trial included 60 patients with MDD, of whom 43 entered modified intention-to-treat analysis. A probiotic supplement or indistinguishable placebo containing maltose was administered over 31 days in addition to treatment as usual for depression. Participant scores on the Verbal Learning Memory Test (VLMT), Corsi Block Tapping Test, and both Trail Making Test versions as well as brain-derived neurotrophic factor levels were assessed at 3 different time points: before, immediately after and 4 weeks after intervention. Additionally, brain activation changes during working memory processing were investigated before and immediately after intervention.
RESULTS
We found a significantly improved immediate recall in the VLMT in the probiotic group immediately after intervention, and a trend for a time × group interaction considering all time points. Furthermore, we found a time × group interaction in hippocampus activation during working memory processing, revealing a remediated hippocampus function in the probiotic group. Other measures did not reveal significant changes.
LIMITATIONS
The modest sample size resulting from our exclusion of low-compliant cases should be considered.
CONCLUSION
Additional probiotic supplementation enhances verbal episodic memory and affects neural mechanisms underlying impaired cognition in MDD. The present findings support the importance of the gut microbiota-brain axis in MDD and emphasize the potential of microbiota-related regimens to treat cognitive symptoms in depression.
CLINICAL TRIAL REGISTRATION
clinicaltrials.gov identifier NCT02957591.
背景
在重度抑郁症（MDD）中，认知功能障碍强烈导致功能障碍，但在当前的治疗中几乎没有得到解决。需要新的治疗策略来解决抑郁症中的认知症状。由于肠道微生物群-大脑轴与抑郁症和认知有关，我们研究了 4 周高剂量益生菌补充对抑郁症认知症状的影响。
方法
这项随机对照试验纳入了 60 名 MDD 患者，其中 43 名进入了改良意向治疗分析。在常规抗抑郁治疗的基础上，在 31 天内给予益生菌补充剂或含有麦芽糖的不可分辨安慰剂。在 3 个不同时间点（干预前、干预后即刻和 4 周后）评估参与者在词语学习记忆测试（VLMT）、Corsi 块打点测试和两种追踪测试版本上的得分，以及脑源性神经营养因子水平。此外，在干预前和干预后即刻还研究了工作记忆处理过程中的大脑激活变化。
结果
我们发现，在干预后即刻，益生菌组的 VLMT 即时回忆明显改善，考虑所有时间点时，还出现了时间×组的交互作用。此外，我们发现工作记忆处理过程中海马激活的时间×组交互作用，表明益生菌组的海马功能得到了改善。其他测量指标没有显示出显著变化。
局限性
应该考虑到我们排除低依从性病例导致的样本量较小。
结论
额外的益生菌补充增强了词语情节记忆，并影响了 MDD 中认知障碍的神经机制。目前的研究结果支持肠道微生物群-大脑轴在 MDD 中的重要性，并强调了与微生物群相关的方案治疗抑郁症认知症状的潜力。
临床试验注册
clinicaltrials.gov 标识符 NCT02957591。
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