Effects of early-life stress on social functioning in depression: A systematic review and meta-analysis of mouse and rat studies

Abstract

Depression is one of the most prevalent mental disorders worldwide, in which social impairments negatively impact daily functioning of those affected. Early stressful experiences have lasting effects on brain development and behavior, which further amplifies vulnerability to this disorder. While the link between early-life stress (ELS) and higher risk of depression is well-established, it remains unclear whether stress timing exposure—i.e., pregestational stress, prenatal ELS or postnatal ELS— affects social functioning severity in depressed individuals. Rodent models are of translational value to study whether stress timing modulates the ELS impact on depression-related social behaviors. Therefore, our aim was to determine whether there is an overall effect of pregestational stress, prenatal ELS and postnatal ELS exposure on a spectrum of depression-related social behaviors in mice and rats; and, whether species, sex, age at testing, and cumulative stress duration modulate such effects. After a comprehensive database search in PubMed and EMBASE, 295 publications were included. Social affiliation and attachment were reduced as a consequence of stress exposure, regardless of the timing. Social communication was not negatively affected by exposure to prenatal or postnatal ELS, while social cognition was impaired in animals exposed to postnatal ELS. Only sex mediated the effect of prenatal ELS on social affiliation and attachment, in which males but not females exhibited reduced social affiliation and attachment following prenatal exposure. These findings underscore the nuanced role of timing in the impact of ELS on depression-related social behaviors, emphasizing the need for further research considering the sex- and social-domain specific effects.