Translational Approach to Social Isolation During a Global Pandemic: Hippocampal Somatic Mutation and Stress

Objective: The coronavirus disease-2019 (COVID-19) pandemic's social isolation has significantly impacted mental health, increasing depression and anxiety. This study explores the effects of social isolation on both humans and mice, focusing on behavioral changes and hippocampal protein expression. It also investigates genetic alterations through single-cell RNA and whole-genome sequencing (WGS).

Methods: Here we conducted behavioral studies, protein expression studies, single-nucleus sequencing (snRNAseq), and WGS of the hippocampus of mice that underwent early maternal separation and social isolation, and a demographic study of community populations who had been self-quarantined owing to COVID-19 exposure to investigate the link between somatic mutations and stress due to social isolation.

Results: The demographic study demonstrated more negative mental health findings among individuals who live alone or are single. Mice subjected to early maternal separation and social isolation demonstrated increased anxiety-like behaviors and stress-related corticotropin-releasing hormone receptor 1, and neurogenesis-related sex-determining region Y-box 2 and doublecortin expression. In snRNA-seq, differences, such as transthyretin increase, were observed in the maternal separation group, and somatic mutations, including insertion in the intron site of Tmem267, were observed in the social isolation group on WGS.

Conclusion: The results of this study suggest that stress, such as social isolation, can cause changes at the genetic level, as well as behavioral and brain protein changes.