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.

Else Schneider, Jessica P K Doll, Nina Schweinfurth, Cedric Kettelhack, Anna-Chiara Schaub, Gulnara Yamanbaeva, Nimmy Varghese, Laura Mählmann, Serge Brand, Anne Eckert, Stefan Borgwardt, Undine E Lang, André Schmidt

Journal: Journal of psychiatry & neuroscience : JPN 2023;48(1):E23-E33

PMID: 36653035

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Plain Language Summary

Major depressive disorder (MDD) is often thought of as being solely a mood disorder. However, several studies have shown that sufferers can also experience decreased brain function such as memory loss and poor attention. Current therapies for MDD focus on the balancing of mood and leaves the problem of reduced brain function unattended. The gut microbiota has recently been shown to influence brain function and altered gut microbiota composition has been seen in individuals with MDD. Targeting the gut microbiota may therefore represent a novel target for MDD treatments. This secondary analysis of a randomised control trial aimed to determine whether a probiotic multistrain supplement could improve brain function in 60 individuals with depression. The results showed that probiotics improved the brain function in two different ways, the immediate recall of words, and the improvement of decreased neural function in the hippocampal part of the brain, which has been associated with MDD. It was concluded that probiotic supplementation can enhance verbal episodic memory and improve neural function associated with impaired brain function in MDD. This study could be used by healthcare professionals to understand that the health of the gut microbiota can have an influence on brain function and that probiotics may help individuals with MDD who are suffering from poorer memory.

Abstract

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.

Address: 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) [email protected].

DOI: 10.1503/jpn.220117