Social isolation and the brain: effects and mechanisms

Abstract

An obvious consequence of the coronavirus disease (COVID-19) pandemic is the worldwide reduction in social interaction, which is associated with many adverse effects on health in humans from babies to adults. Although social development under normal or isolated environments has been studied since the 1940s, the mechanism underlying social isolation (SI)-induced brain dysfunction remains poorly understood, possibly due to the complexity of SI in humans and translational gaps in findings from animal models. Herein, we present a systematic review that focused on brain changes at the molecular, cellular, structural and functional levels induced by SI at different ages and in different animal models. SI studies in humans and animal models revealed common socioemotional and cognitive deficits caused by SI in early life and an increased occurrence of depression and anxiety induced by SI during later stages of life. Altered neurotransmission and neural circuitry as well as abnormal development and function of glial cells in specific brain regions may contribute to the abnormal emotions and behaviors induced by SI. We highlight distinct alterations in oligodendrocyte progenitor cell differentiation and oligodendrocyte maturation caused by SI in early life and later stages of life, respectively, which may affect neural circuit formation and function and result in diverse brain dysfunctions. To further bridge animal and human SI studies, we propose alternative animal models with brain structures and complex social behaviors similar to those of humans.

Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior

“…Enhancing inhibitory neuronal circuits via overexpressed MG-BDNF may increase the density and function of inhibitory synapses. Previous studies have also revealed increased inhibitory inputs in mPFC layer V pyramidal cells in j-SI mice and other abnormalities in inhibitory interneuron functions in the mPFC [11,15,17,18].…”

“…Juvenile social deprivation harms the neural circuits and glial cells of the medial prefrontal cortex (mPFC) [11][12][13][14][15][16][17][18], which is a control center of social behaviors [19]. Previously, we reported the involvement of microglia in juvenile social isolation and future social impairment [13].…”

Social Isolation, Physical Activity, and Subsequent Changes in Cognition Among Middle- and Older-Aged Adults: Results From the Canadian Longitudinal Study on Aging

“…Relatedly, the negative effects of social isolation on cognitive health may accumulate over years or decades and therefore not be detectable until late life. This remains unknown, however, as much of the relevant animal and human studies have not considered lifespan changes in these associations (47,54). Moreover, the presence of indirect effects yet absence of total effects (as occurred in older men) might be a statistical phenomenon, resulting from greater statistical power to detect indirect effects compared with total or direct effects (55,56).…”

Mitochondria: It is all about energy

“…The benefits of social interaction include better mental health, improved sleep quality, increased life expectancy, and improved immunological and metabolic health ( Xiong et al, 2022 ). Related to metabolic changes observed in loneliness or chronic isolation, HPA axis chronic activation leads to the elevated secretion of cortisol, increased blood glucose, glycogenolysis, and insulin resistance that ends up in engaging in unhealthy habits and decreasing satiety signaling.…”