Researchers at Xi’an Jiaotong University, China, have explored the role of long-term antibiotic use in early life and risk to mental health.
Anxiety, depression and alcohol dependence are common mental disorders that are becoming serious health problems across the world. Common mental traits and disorders are typically multifactorial diseases that are impacted by both genetic and environmental factors. Environmental risk factors, including smoking, stress and early adverse childhood experiences, have been associated with depression and anxiety. While there have been reports of heritability, the genetic mechanism of mental health remains largely unknown.
Previous epidemiological and experimental studies have observed significant correlations between long-term antibiotic use during early life and mental traits. Antibiotic treatment during early adolescence has been shown to have a permanent impact on brain function in mice. In addition, microbiota depletion due to chronic antibiotic use in mice has impacted their anxiety and cognitive behaviours. Nonetheless, the implications of long-term use on the variations of mental traits is not well understood. In particular, researchers have yet to explore the potential interaction between long-term antibiotic use during early life and genes on risks of mental health.
Long-term antibiotic use during early life
In this study, published in Neuropsychopharmacology, researchers conducted an observational study. They assessed associations between long-term antibiotic use during early life and mental health in the UK Biobank. In addition, they performed a gene-environment-wide interaction study (GEWIS) based on these observations. This aimed to determine the effects between genes and long-term antibiotic use on the development of mental traits. Finally, a gene ontology (GO) analysis of the identified interacting genes was performed.
The researchers found positive associations between long-term antibiotic use during early life and anxiety, depression and the frequency of smoking. Moreover, they found negative associations between long-term use during early life and remembrance, intelligence and the frequency of drinking.
The GEWIS identified multiple significant genes interacting with long-term antibiotic use during early life. This included ANK3 (rs773585997, p value = 1.78 × 10−8) for anxiety and STRN (rs140049205, p value = 1.88 × 10−8) for depression.
GO analysis identified six GO terms enriched in the identified genes interacting with long-term antibiotic use during early life for anxiety. This included GO:0030425-dendrite (p value = 3.41 × 10−2) and GO:0005886-plasma membrane (p value = 3.64 × 10−3).
This study has highlighted that long-term antibiotic use during early life is associated with mental traits. The authors suggest that such long-term treatment would alter the gut microbiome. This may influence gut-brain communication and therefore alter brain development. They hope that these results will provide insight into the pathogenicity of mental health.