A critical analysis of stress-related gene regulation in isolated and connected individuals.

This letter responds to the article by Yvonne S. Yang et al. (2024) on the relationship between social isolation, loneliness, and stress-related gene expression, published in Brain, Behavior, and Immunity. The authors' recruitment methods and use of genome-wide transcriptional profiling to assess the Conserved Transcriptional Response to Adversity (CTRA) are highly commendable, offering a comprehensive understanding of how social isolation impacts immune gene expression. However, we raise concerns about the small sample size, demographic limitations, cross-sectional design, and lack of correction for multiple comparisons, which may affect the study's generalizability and validity. Despite these limitations, the study provides valuable insights, paving the way for future research to explore the complex interactions between social isolation, loneliness, and health. We recommend that future studies address these limitations to enhance the robustness of findings and the development of effective interventions.