Abstract
Objective: During the COVID-19 pandemic, quarantine and staying at home is advised. The social relationship between people has become deficient, and human social isolation (SI) has become the consequence of this situation. It was shown that SI has made changes in hippocampal neuroplasticity, which will lead to poor cognitive function and behavioral abnormalities. There is a connection between SI, learning, and memory impairments. In addition, anxiety-like behavior and increased aggressive mood in long-term isolation have been revealed during the COVID-19 outbreak.
Methods: Term searches was done in Google Scholar, Scopus, ScienceDirect, Web of Science and PubMed databases as well as hand searching in key resource journals from 1979–2020.
Results: Studies have shown that some drug administrations may positively affect or even prevent social isolation consequences in animal models. These drug treatments have included opioid drugs, anti-depressants, Antioxidants, and herbal medications. In addition to drug interventions, there are non-drug treatments that include an enriched environment, regular exercise, and music.
Conclusion: This manuscript aims to review improved cognitive impairments induced by SI during COVID-19.
Keywords: COVID-19, social isolation, learning and memory, anxiety, drug treatments, non-drug treatments
Introduction
Social interaction has a crucial role in human well-being, both mentally and physically (1).  Human social isolation (SI) happens when the social relationship between individuals become deficient (2). Moreover, it mostly occurs when the number of individuals, who are members of social links, decrease, or the qualification of social relations, diminishes. During SI, people experience unpleasant situations mentally, emotionally, and spiritually (3, 4). Some conditions force individuals to leave human groups and reduce their social interactions, presence in the population, and group activities. Being single, getting a divorce and separation may also result in isolation (2, 5). Further, weak connections and lack of social support have shown to be significant risk factors of isolation, which result in loneliness, stress, and committing suicide (6, 7). Meanwhile, some infectious diseases like COVID-19, AIDS, and some physical disorders have shown to develop SI in humans (8, 9).
Adverse effects on cognition and behavior, decision-making, and pain perception are followed by social isolation (10, 11). SI has shown to change the immune system, glutamate system, and hormones (12, 13). Besides, cardiovascular disease, high blood pressure, stroke, and developmental neurodegenerative diseases have occurred during SI (14). Depression was also induced while motor dysfunction decreased during isolation (15-17). Some evidence demonstrated more oxidative stress and inflammation because of increased IL-1ß, cytokines, and brain macrophages during SI (18). Isolation and loneliness lead to a higher rate of morbidity, mortality, and it is strongly related to chronic disease with death in adults (17, 19).
Previous researches have shown there is a relation between SI and alternations in the hippocampus. According to studies, changes in hippocampal neuroplasticity will lead to poor cognitive function and behavioral abnormalities (20, 21). There is a connection between SI, learning, and memory impairments as well. Some studies have reported that environmental factors play a significant role in brain development and cognitive function in rodents, which directly affect learning and memory performance (22, 23). Results suggest that SI as the lack of presence of others or the few numbers of meaningful relationships is vastly associated with many aspects of memory and learning impairment (24, 25). Morris Water Maze’s outcomes have also shown spatial learning and memory dysfunction during isolation (26, 27). Other studies have demonstrated inhibition of autophagy by the production of some factors (28), deficit spatial learning and memory, social recognition memory, reversal learning, and short-term memory during SI periods (29). Alternatively, some studies have shown that isolated environments did not affect spatial learning and memory, spatial reference memory, reversal learning, and short-term memory. Moreover, in some cases, results have suggested that memory and learning performance has improved due to social isolation (28, 30).
Animal research indicated depression, anxiety-like behavior, and increased aggressive mood in long-term isolation (31, 32). Moreover, the time spent in the open arms of the Elevated plus Maze has decreased as a consequence of higher anxiety (33). Chronic stress has taken place as a feature of anxiety and depression.
The human species depends on social behavior and social interaction. Being social helps humans survive and solve problems; while, weak social interaction negatively affects social memory and sociability during SI (34, 35). There has been a correlation between neuroendocrine disability and impairments in neurogenesis of the hippocampus and decline in BDNF expression (36).
The results have also revealed that SI has developed Alzheimer’s disease, and it has exacerbated spatial learning impairment in aged mice (37). Motor activity is not affected according to open field outcomes; however, chronic stress during SI has shown to the deficit the motor function in rodent models of Parkinson’s disease (38, 39).