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.

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.

Clinical, gut microbial and neural effects of a probiotic add-on therapy in depressed patients: a randomized controlled trial.

A promising new treatment approach for major depressive disorder (MDD) targets the microbiota-gut-brain (MGB) axis, which is linked to physiological and behavioral functions affected in MDD. This is the first randomized controlled trial to determine whether short-term, high-dose probiotic supplementation reduces depressive symptoms along with gut microbial and neural changes in depressed patients. Patients with current depressive episodes took either a multi-strain probiotic supplement or placebo over 31 days additionally to treatment-as-usual. Assessments took place before, immediately after and again four weeks after the intervention. The Hamilton Depression Rating Sale (HAM-D) was assessed as primary outcome. Quantitative microbiome profiling and neuroimaging was used to detect changes along the MGB axis. In the sample that completed the intervention (probiotics N = 21, placebo N = 26), HAM-D scores decreased over time and interactions between time and group indicated a stronger decrease in the probiotics relative to the placebo group. Probiotics maintained microbial diversity and increased the abundance of the genus Lactobacillus, indicating the effectivity of the probiotics to increase specific taxa. The increase of the Lactobacillus was associated with decreased depressive symptoms in the probiotics group. Finally, putamen activation in response to neutral faces was significantly decreased after the probiotic intervention. Our data imply that an add-on probiotic treatment ameliorates depressive symptoms (HAM-D) along with changes in the gut microbiota and brain, which highlights the role of the MGB axis in MDD and emphasizes the potential of microbiota-related treatment approaches as accessible, pragmatic, and non-stigmatizing therapies in MDD. Trial Registration: www.clinicaltrials.gov , identifier: NCT02957591.

Effectiveness of a Mindfulness-Based Mobile Application for the Treatment of Depression in Ambulatory Care: Protocol for a Randomized Controlled Trial.

BACKGROUND: Patients with major depressive disorder (MDD) often experience relapses despite regular treatment with pharmacotherapy and psychotherapy. Further, long waiting lists and more demand than treatment capacity characterize ambulatory settings. Mindfulness-based interventions proved to be effective in relapse prevention in MDD. Next, mindfulness-based interventions in the form of free mobile applications can be an effective augmentation of the treatment as usual and can fill a gap in ambulatory care. OBJECTIVE: Given this background, the aim of this randomized controlled study is to assess the effectiveness of additional MBI via a mobile app on the symptom severity and stress levels, compared to treatment as usual. METHODS: A total of 140 individuals with MDD will be randomly allocated to the intervention or control condition. The intervention consists of the daily use of the mindfulness mobile application Headspace for thirty days (up to 10 minutes a day). The control condition will be treatment as usual. At baseline and four weeks later, the following key outcome dimensions will be assessed: self-rated (Beck Depression Inventory) and experts' rated symptoms of MDD (Hamilton Depression Rating Scale); secondary outcome variables will be blood pressure, heart rate, and respiratory rate and changes in tobacco and alcohol consumption and medication as a proxy of perceived stress. RESULTS: This study was funded in February 2021 and approved by the institutional review board on April 15, 2021, and it started in May 2021. As of December 2021, we enrolled 30 participants. The findings are expected to be published in spring 2023. CONCLUSIONS: We hypothesize that compared to the control conditions, individuals with MDD of the mobile app-condition will have both lower self- and experts' rated symptoms of MDD and more favorable stress-related levels. While the risk for medical events is low, the immediate benefit for participants could be a decrease in symptom severity and reduction of the stress level. TRIAL REGISTRATION: Clinical Trials.gov NCT05060393; https://clinicaltrials.gov/ct2/show/NCT05060393. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/33423.