Analysis of individualized brain–gut association networks and transcriptional patterns in major depressive disorder

Gut Microbiome in Depression with and without REM Sleep Behavior Disorder.

Gut microbiome provides a candidate approach for potential risk stratification in psychiatric populations, and MDD + RBD may represent a biologically distinct depression subtype associated with potential neurodegenerative risk.

Gut microbial biomarkers for major depressive disorder: a cross-sectional study

Background Alterations in the gut microbiota have been associated with a variety of psychiatric disorders, including major depressive disorder (MDD). However, the relationship between MDD and gut microbial communities remains incompletely understood. Most previous studies have primarily focused on gut bacteria, with relatively limited attention to other microbial components. Methods In this study, we analyzed gut microbial profiles from 36 patients with MDD and 36 healthy controls using metagenomic sequencing data. The MaAsLin2 algorithm was applied to identify potential microbial biomarkers associated with MDD. Results A total of 6 bacterial biomarkers and 7 viral biomarkers were identified. The models based on these features demonstrated strong predictive performance, with area under the curve (AUC) values of 0.891 for bacteria and 0.878 for viruses. Notably, the combined bacterial-viral model achieved an AUC of 0.946. These findings were further evaluated through external testing in two unrelated research cohorts. In the Shanxi cohort, the AUC values were 0.825 (bacteria), 0.803 (viruses), and 0.972 (combined model). In the Wuhan cohort, the AUC values were 0.683 (bacteria), 0.693 (viruses), and 0.784 (combined model). Conclusion In summary, our results highlight the potential of gut bacterial and viral biomarkers as candidate biomarkers and potential auxiliary tools for MDD assessment and suggest that integrating multi-domain microbial features may improve prediction accuracy.

Mapping brain connections to inflammatory networks in depression identifies sex-specific neuroimmune networks and neurobiological subtypes

Integrative Multi-Tissue Analysis Identifies Synaptic Gene Networks Specific to Major Depressive Disorder in Women

From gut to brain: data-driven evidence suggests causal contribution of gut-microbiota to major depressive disorder in humans

Abstract Major Depressive Disorder (MDD) is a highly prevalent, severe mental health condition that constitutes one of the leading causes of disability worldwide. While recent animal studies suggest a causal role of the gut microbiome in the pathophysiology of MDD models, evidence in humans is still unclear due to small sample sizes, inconsistent clinical assessment of MDD diagnosis, and methodological limitations regarding causal inference in cross-sectional data. Here, we explicitly address these shortcomings to investigate the potential causal link between the gut microbiome and MDD: First, we replicate previously reported microbiome-depression associations using one of the largest multicenter MDD cohorts for which microbiome data and in-depth diagnostic assessment are available (N = 1,269 MDD patients and controls). We find a significant difference between healthy controls and MDD patients for the relative abundance of four taxa: Eggerthella, Hungatella, Coprobacillus, and Lachnospiraceae FCS020. Second, we employ state-of-the-art, fully data-driven causal inference tools within Judea Pearl's framework, allowing us to derive model constraints from the data rather than relying on potentially strong, unrealistic assumptions. Using this approach, we found evidence for Eggerthella and Hungatella as potential causal contributors to MDD. Furthermore, we show that the potential causal effects of Eggerthella and Hungatella on MDD persist beyond the influence of body mass index, revealing two distinct potential causal pathways linking the gut microbiome to MDD. Finally, the difference in relative abundance of these taxa between healthy and MDD patients was independent of antidepressant medication. Our study provides the first data-driven evidence for a potential causal role of gut microbiota in the pathophysiology of depression in humans.

Edge-centric brain connectomes reveal two molecularly distinct neurobiological subtypes of adolescent major depressive disorder.

This study investigated the neural and molecular bases of individual differences in adolescent MDD patients by integrating a novel edge-centric brain connectome with transcriptomic and neurotransmitter profiles, and identified two robust adolescent MDD subtypes.