Feeling anxious yet? Interpreting findings on drug safety from large healthcare databases

Greta A. Bushnell, Daniel Horton, Tobias Gerhard

Published Year: 05/16/2022

In this issue of Clinical and Translational Science, Yun-Han Wang and colleagues report on a potential link between treatment with proton pump inhibitors (PPIs) and incident depression and anxiety disorders in children. The proposed mechanism between PPI use and anxiety and depression is related to the “microbiota-gut-brain axis.” The microbiota-gut-brain axis and associated health problems have been attributed to multiple inter-related pathways, including microbiota-derived production of neurotransmitters (e.g., serotonin); communications among afferent, efferent, autonomic, and limbic nerves; immune-mediated pathways (e.g., cytokines); and endocrine pathways (e.g., hypothalamic–pituitary–adrenal axis). PPIs are known to dysregulate the microbiome, and microbiome dysregulation has been linked to mental health disorders in animal models and in adult populations.