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Burden of depressive disorders by country, sex, age, and year: findings from the global burden of disease study 2010

Several critical questions remain unresolved: (1) most existing studies are confined to animal and cellular models, with a notable lack of large-scale population-based investigations and clinical validation, thereby impeding translational application

This proposed mechanism has been directly validated in animal models where the surgically severed vagus nerve attenuated anxiety- and depression-like behaviors in mice after oral antibiotic administration, providing direct evidence for neuropsychiatric effects induced by antibiotics through the gutbrain axis (Joo et al., 2023)

For example, Vitamin D deficiency may reduce intestinal calcium absorption, causing gut stasis and subsequent IPC, which would allow gut microbiota to transfer more endotoxins into the blood and trigger inflammatory cytokines production within the CNS (249)

Improved treatment of ligands and coupling effects in empirical calculation and rationalization of p K a values