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What happens to your brain when you isolate?

These include elevated levels of anxiety and depression, deterioration of mental health, changes in diet and increased suicidal ideation, in addition to less physical activity and higher levels of experienced loneliness.

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Various emerging studies carried out under COVID-19 lockdown suggest that social distancing has had considerable psychological and behavioural consequences. These include elevated levels of anxiety and depression, deterioration of mental health, changes in diet and increased suicidal ideation, in addition to less physical activity and higher levels of experienced loneliness. Importantly, there have been considerable interindividual differences, with some people experiencing limited effects, but others experiencing more serious consequences. The prevalence of reported loneliness was higher, for example, among those who were self-isolating alone and unemployed, and lower in people who were married or living with a partner114. Rates of loneliness were twice as high among people who met clinical criteria for depression, anxiety and post-traumatic stress disorder than they were in the rest of the population. Greater difficulties with emotion regulation and poorer sleep quality were also commonly associated with loneliness. On average, older people were found to show greater satisfaction with life, higher levels of social cohesion, less concern about family members contracting COVID-19 and lower levels of self-reported panic, depression, emotional disturbances and risk perception115. Best and colleagues115 also showed evidence that, compared with men, women experienced more overall distress and higher levels of panic, depression, emotional disturbances and concerns about contracting COVID-19 and about the safety of their family—a finding in line with the generally greater intimacy of women’s friendships (see above). Individuals who relied on credible sources of information, such as mainstream news, employer-based information and public health announcements, reported less overall COVID-19 distress, panic, depression and emotional disturbance, as well as greater satisfaction with life and social cohesion115. Various physical factors were also identified. These effects might be exacerbated by confinement-induced decreases in physical activity levels and increases in sedentary behaviour, for example116. Such a lifestyle has been shown to precipitate rapid deterioration of cardiovascular health and premature death, especially through transitory ischemic attacks and strokes117. One seminal study118 used an innovative experience-sampling approach to investigate the naturally occurring changes in everyday cognition before and during the first COVID-19 lockdown in the UK (Fig. 4). This naturalistic experiment is based on the notion of ‘mindwandering’, a form of daydreamed, spontaneous thought that is typically unrelated to the ambient environment and known to vary along several dimensions such as vividness, content and time direction to past/present/future. These sometimes random, sometimes purposeful internally paced episodic mental scenes tend to occur especially commonly when people are not actively focused on a mental task—which makes experience sampling at random time points during the day a particularly attractive research tool. Fig. 4: Lockdown entails changes in ongoing random thoughts using multidimensional experience sampling. a,b, In separate time points before and during the first lockdown during the COVID-19 pandemic in the UK, participants were queried by experience sampling at various moments, five random times per day for a whole week118. The participants were prompted at random times in their everyday lives to obtain multiple reports describing features of their ongoing thoughts and the context in which they occurred (for example, social environment, activity and location). The aim was to illuminate how specific features of the stay-at-home order impacted people’s thinking in daily life. Multidimensional experience sampling assessed people’s thoughts across 22 assessment dimensions, including aspects of social thinking and future-directed problem-solving. Panel a shows a comparison of the overall responses to the experience-sampling queries. During the lockdown, both groups of 59 younger (18–35 years old) and 23 older adults (55+ years old) reported feeling more alone. Panel b shows where the participants were when being queried during the lockdown (most were at home). The collective findings show that the lockdown led to significant changes in ongoing thought patterns in daily life. These changes were associated with changes to daily routines that occurred during lockdown. Figure reproduced with permission from ref. 118. Full size image The participants’ ongoing thoughts and the contexts in which they occurred (for example, social environment, activity and location) were randomly sampled in real time over five days. Future-directed problem-solving was lower during lockdown, especially in older individuals (55+ years old) and in those who engaged in regular real-world interaction with others. Yet, this was less prominent when participants were interacting physically as opposed to virtually. Before the first lockdown was imposed, younger participants (18–35 years old) reported engaging in less vivid imagery during introspection when they were alone than when they were interacting with others. But during lockdown, the younger participants reported more vivid imagery when they were alone than when they were interacting with others. However, the kinds of episodic social cognition normally observed in interactive environments were greater during lockdown, this being more apparent across all forms of interaction when compared with not interacting at all. Detailed task focus was more apparent when interacting virtually than in other contexts. Taken together, this behavioural comparison of moment-to-moment spontaneous thoughts before versus during COVID-19 suggests that the lockdown led to notable changes in ongoing thought patterns in daily life and that these changes were associated with changes to daily routines before versus after the public health restrictions were in place, to which individuals may have conformed to varying degrees. In particular, the naturalistic thought probes have characterized how social encounters are an important influence on our day-to-day thinking. Shifting opportunities for regular social contact following the stay-at-home orders are likely to have changed the expression of people’s ongoing in-the-moment thought tendencies. It is clear that COVID-19 has also taken a heavy toll in terms of mental health, especially for some strata in the wider population. Robb and colleagues119 investigated the psychological effects of COVID-19 lockdown on 7,127 cognitively healthy older adults (mean age, 70.7; s.d., 7.4) from the UK. The authors found an association between subjective loneliness and increased indicators of depression and anxiety following lockdown. More than half of the respondents reported feeling lonely, and a quarter lived alone. These proportions were higher in women than in men. Around 12.3% and 12.8% of the respondents reported increased symptoms of anxiety and depression, respectively, during lockdown. Again, these proportions were higher for women than for men. Compared with those who never felt lonely, individuals reporting that they often felt lonely had 11- and 17-times-higher odds of feeling more anxiety and depression, respectively, during lockdown. Compared with men, lonely women were twice as likely to report worse symptoms of depression, whereas lonely men were around 5% more likely to report greater anxiety than females. Those who lived alone were more likely to report feeling worse on components of anxiety and depression than those living with others. Compared with individuals who reported daily contact, those reporting two to six occasions of online social contact per week had a 19% lower risk of feeling greater anxiety. These outcomes are broadly in line with what our review of the dynamics of human social networks (see above) would lead us to expect.

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Interestingly, remote contact with friends or family via technology did not significantly alter the risk of reporting feeling worse on components of depression. Robb and colleagues119 reasoned that “Wider access to technology may help buffer loneliness and isolation that lead to worsened mental health. Older people, however, are more likely to have limited ability to access technology, most likely representing the more vulnerable of this demographic … As in-person intervention strategies during pandemics may be limited or impossible, the use of technologies, such as apps, may remain an important tool, albeit limited by the digital divide, thus potentially excluding significant numbers of particularly vulnerable older people.” Adding further detail to the reported effects of social isolation from social distancing during COVID-19 in a pre-existing, longitudinal UK cohort119, in males, smokers were more likely to report greater depression than non-smokers, with no association observed among females. In women, a three-unit increase in alcohol consumption per week (approximately one large glass of wine) was associated with a 22% lower probability of reporting an improvement in components of depression. Additionally, as many as 40% of the cohort reported sleep disturbances, possibly because worry and ruminating thoughts provoke cognitive arousal and may disturb stress-related cortisol homeostasis, resulting in poorer sleep. However, as an important caveat, Robb and colleagues did not have pre-pandemic anxiety or depression measures to compare against the ones acquired during physical distancing mandates, which weakens causal attribution. Those reporting poor sleep at least three times per week had eight- and seven-times-higher odds of reporting worse symptoms of anxiety and depression, respectively. Robb and colleagues119 also found that those who were single/widowed/divorced and/or who lived alone were also at increased risk of reporting worse symptoms of depression and anxiety following COVID-19 lockdown, especially men. Indeed, being widowed or divorced as a risk factor for worse mental health has been reported in COVID-19 cohort studies in Spain (n = 3,055)120 and China (n = 1,060)121, although these were younger cohorts. Overall, women were more likely to report worse components of anxiety and depression than men, with this observation replicated in different age groups and in different countries, including Demark, Spain, Italy, Turkey and Iran119. In a comparison of outcomes before and during the pandemic at the psychological and behavioural levels, Niedzwiedz and colleagues122 analysed data from almost 10,000 adults in the longitudinal arm of a nationally representative sample (the UK Household Longitudinal Study). In addition to increased regular and binge alcohol consumption, psychological distress rose, especially in women and young adults generally, as well as in the Asian community and among individuals with a degree education. Robinson and colleagues123 conducted a systematic meta-analysis of 65 longitudinal studies and documented an increase in mental health burden, particularly in the months after lockdown, especially in depressive symptoms, anxiety and mood disorder symptoms in American, European and other samples. Several of these changes during COVID-19 were especially pronounced in individuals with pre-existing physical conditions, which the authors interpreted as likely to reflect an elevated risk of infection. Moreover, Zaninotto and colleagues124, who examined the profiles of >5,000 adults from the English Longitudinal Study of Aging, reported that depression, anxiety, loneliness and poor quality of life increased in the months after the pandemic started. The manifestations were stronger in certain population strata: women, older individuals, and those who live alone or are less affluent. The collective findings from these longitudinal population investigations converged on a major breakdown in mental health and health-related behaviours throughout the COVID-19 pandemic in 2020. Targeted monitoring and psychological interventions are suggested by these authors, especially for more vulnerable parts of the community, including more socially isolated individuals (such as single, widowed and divorced people), who suffered disproportionately. Only very few longitudinal brain-imaging studies relevant to COVID-19 have been published so far. Douaud and colleagues sampled 782 UK Biobank participants who had been brain-scanned before the pandemic and have been re-scanned during the pandemic125. Of these, 394 had been infected by COVID-19, and 388 acted as matched controls. Brain changes due to the infection itself were linked to a loss of grey matter (with cortical thickness and mean diffusivity measures as proxies to capture tissue changes) in the left parahippocampal gyrus, the left lateral orbitofrontal cortex and the left insula. When looking over the entire cortical surface, these results extended to a set of brain circuits including several nodes of the prefrontal, parietal and temporal default network, in addition to the anterior cingulate cortex and olfactory circuits. These differences in brain correlates of infection were associated with increased cognitive decline, as evidenced by significantly more time required to complete the numeric (A) and alphanumeric (B) version of the Trail Making Test. In addition, a decrease in whole brain volume suggests a diffuse loss of grey matter superimposed onto the more regional effects. In addition to the study’s unique pre- and post-COVID-19 data and careful matching of the patients and controls for age, sex, scan interval and ethnicity, rigorous diagnosis of infection made it possible to test for brain correlates of the disease in a way that was statistically more precise than would have been the case for cross-sectional post-infection differences alone. Although the social consequences of COVID-19 infection were not followed up, the reduced grey matter volume, especially in units of the default network, suggests that a loss of social skills and social network size is a likely outcome, although inferring causal directionality is challenging.

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The rare evidence on brain changes in medial-temporal limbic, insula and orbitofrontal cortex seems to bear similarities to longitudinal studies in non-human primates. One brain-imaging study of dopaminergic function compared macaque monkeys housed in social isolation for 1.5 years and during later social housing with other monkeys126. The repercussions of diminished frequency and intensity of social interaction may be traced to dopaminergic neurotransmitter pathways implicated in reward processing, such as in the orbitofrontal cortex. Indeed, after social rehabilitation, less socially interactive males with fewer grooming opportunities displayed hyperactive dopamine responses not present before the isolation condition. The authors concluded that experimentally altering the social richness in the environment led to reward-related neural plasticity effects. The medial-temporal limbic system in turn has been related to plasticity changes in social network sizes in non-human primates, based on regularity of social contact in longitudinal research33. The authors also flagged changes in the prefrontal cortex structure, which may relate to social hierarchy organization that breaks down in times of scarce social interaction or changing social order with lower predictability. Finally, the insula was emphasized in longitudinal research in free-ranging monkeys, and its changes were interpreted to relate to affiliative behaviour and forms of empathy towards others34, instrumental for maintaining the regular grooming social network. As reflections for future research on social isolation, among the elderly whose social circles are already contracting, we might expect isolation to hasten the rate at which friendships decay and are ultimately lost, resulting in increased susceptibility to mental (for example, cognitive decline, depression and anxiety) and physical (for example, stress, diminished cardiovascular health and impaired immune defence) deterioration over the following decade. Given that most of the social skills needed for the adult world are acquired through peer interaction rather than interactions with adults, we might anticipate some slowdown in the rate of social development in adolescents, possibly resulting in long-term loss in social skills. However, an alternative interpretation might be that the elderly tend to have smaller, more tightly knit, more family-oriented social networks that buffer them against the worst effects of isolation, whereas young adults usually have wider social networks in which peripheral friendships play an important casual role. Viewed from this angle, younger adults would be expected to experience more loss of social capital during the pandemic, with higher costs for mental and physical health. Follow-up studies will be needed to determine which causal sequence is correct. Either way, the population stratum that may be the least likely to be affected by lockdown is young adults: this age group’s strong natural desire to be social whenever possible is likely to result in a rapid re-establishment of normal social interaction patterns.

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