Probiotic Administration Positively Influences Cognition in Subjects with Major Depressive Disorder

by | Aug 1, 2023 | 2023, Brain Health, Depression, Probiotics

Written by Taylor Woosley, Staff Writer. 4-week supplementation of probiotics (a daily dose of 900 billion CFU/d) improved immediate recall and reduced hippocampal activation in subjects with depression compared to placebo. 

depressionMajor depressive disorder (MDD) is one of the most common psychiatric disorders and the lifetime prevalence of MDD in adults in the United States is estimated to be 17%1. MDD has been associated with alterations in various biological systems and with alterations in brain structure and function, gastrointestinal factors, immunology, endocrinology (including neurotransmitters), neurotrophic factors, hormones, and oxidative stress2. Around 40%-50% of MDD patients experience an inadequate response to antidepressant therapy, resulting in the need for new treatments3.

Probiotics, live microorganisms that have demonstrated beneficial effects on human health, have gained interest in recent years for their potential impact on symptoms of MDD4. Probiotics effect on mental states involves not only improvements in gut wall integrity and suppressed inflammation, but also regulation of the hypothalamic-pituitary-adrenal axis, thereby affecting the response to stress modulation5. Research has shown that probiotic administration has shown benefits including improved mood, reduced depression, and anxiety scores, improved neurocognitive performance, and reduced stress-induced memory changes6.

Schneider et al. conducted a secondary analysis of their randomized controlled trial analyzing the efficacy of a probiotic multi-strain supplement add-on therapy in improving cognitive symptoms in subjects with depression. Subject inclusion consisted of having a primary diagnosis of MDD, with a Hamilton Rating Scale for Depression (HAM-D) with scores greater than 7 (mild depression), who were at least 18 years, and were undergoing treatment for depression, and had no psychiatric comorbidities.

Subjects (n=43) were divided into either the probiotic treatment group (n=19) or the control (n=24). Participants followed their usual treatment, along with consuming a probiotic supplement for 4 weeks. The supplements contained 8 different strains, resulting in a daily dose of 900 billion CFU/d. The control group consumed a placebo containing maltose which could be mixed in a cold drink. Before the study and right afterwards, subjects partook in assessments relating to cognitive measures, brain imaging, and blood sampling. Participants completed a final follow-up assessment 4-weeks after treatment which included all measures except for brain imaging.

Cognitive measures included using the Corso block-tapping test and the Trail Making Test (TMT) A and B to analyze memory capacity, working memory, attention, and mental flexibility. To assess serum BDNF levels, fasted blood samples were obtained. Subjects underwent a 2-back task using fMRI to assess probiotic-related brain activation changes during working memory processing. 2-sample t tests and the corresponding effect size (Cohen d) were utilized to compare change scores from baseline to post-intervention regarding changes in cognition and BDNF. Pearson correlation and Fisher z were used to compare correlations between groups regarding associations between cognitive performance, brain activation, and BDNF levels.

At the beginning of the study, both groups had similar immediate recall scores (t49.05 = 0.72, p = 0.48). However, a significantly different change score between groups was noted when comparing baseline and post-intervention assessments (t37.86 = -2.16, p = 0.037, d = -0.67), with the probiotic group exhibiting a lower mean ± SD change scores than the control (-7.35 ± 4.86 v. -3.57 ± 6.23). When comparing the immediate memory performance over the 3 time points, a significant group effect was found (F1, 49.04 = 5.03, p = 0.029), along with a significant time effect (F2, 76.12 = 2.55, p = 0.084). BDNF levels in the probiotics group from baseline to post-intervention assessment was -0.28 ± 12.01, indicating a slight increase in BDNF levels. Main findings of brain activation during working memory tasks showed significant differences in activation changes over time between groups in the left hippocampus for the 0-back condition (ppeak(FWE) = 0.001) and the 2-back condition (ppeak(FWE) = 0.031).

Results of the study show that 4-week probiotic supplementation improved verbal episodic memory and reduced hippocampal activation. Further research on probiotic treatment for mood disorders is necessary to better comprehend probiotic impact on symptom relief. Study limitations include the small sample size and short study duration.

Source: Schneider, Else, Jessica PK Doll, Nina Schweinfurth, Cedric Kettelhack, Anna-Chiara Schaub, Gulnara Yamanbaeva, Nimmy Varghese et al. “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.” Journal of Psychiatry and Neuroscience 48, no. 1 (2023): E23-E33.

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Posted August 1, 2023.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

References:

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