Julia Ye ’21 and Zachary Pickell ’21


You’re stuck in your house, taking responsibility and doing your part in social distancing. You’ve exhausted Netflix’s contents. Hulu, Disney+, YouTube–it’s all a blur. A constant cycle of switching between one time-wasting social media platform to another. There’s only so many times you can reread the same couple books. You take a boredom nap, wake up to eat a meal. Does it count as breakfast or dinner? Who honestly knows at this point? Your university has shut down everything, classes are online, and everyone had to move back home. You haven’t had non-familial in-person social contact in weeks. You keep waiting to wake up because it feels like a dream, but reality is slowly sinking in. This is life in self-isolation due to the pandemic called COVID-19, or better known as the Coronavirus. And no, this virus isn’t caused by drinking Corona Beer. 

Lately, we have heard a lot about stay home stay safe orders and social distancing, but there is a stark difference between self-isolation and social isolation. Social distancing is when you deliberately increase the physical space between yourself and others, but you can still socialize face-to-face with others. Self-isolation is an elevated form of social distancing, where you might be symptomatic, should remain at home, have essential supplies delivered, but can still connect with others through virtual means1,2. On the other hand, social isolation is when you lose communication with others– even virtually3. As you can imagine, it can be pretty easy for self-isolation to turn into social isolation–especially for people who live alone, are not comfortable with technology, or do not have access to it. After reading this paper, we hope you understand the science behind why maintaining healthy social networks during this time is important for your mental health. 

Explaining the science 

Okay, let’s break it down to the basics first and answer the question: what is loneliness? Simply put, it’s the subjective distressed feeling of being alone or separated that arises when your social network is deficient or lacking4. Since it is such a deeply complex trait, it’s difficult to attribute loneliness to a single gene. Instead, recent work has proposed that a network of genes work together to affect loneliness. Not only do these genes interact and regulate each other, but they also interact with different environmental factors to yield a person who is potentially more susceptible to loneliness. Also, these genes are somewhat inheritable, which sucks. Before we go further, let’s do a quick refresher on DNA and genes.

Quick Science Catch-up: 

Genes are coded into our DNA and can eventually turn into a protein that functions in our body. For a gene to be a protein, the sequence of bases in the DNA must first be transcribed into RNA, then the RNA can be translated into a protein. Essentially, this process can be thought about in terms of baking a cake. The DNA represents the recipe you need to use to bake the cake, while the cake is similar to the final product or protein. A proper yummy cake can be seen as a fully functional protein in the body, and if you followed the directions and added the correct amount of each ingredient, then you should end up with a yummy cake. However, if you add too much or too little of certain ingredients, which is similar to the RNA expressed in each cell, then you will not have a yummy cake or fully functional protein at the end.

  To add another layer of complexity, there is also something called epigenetics. So, you have DNA, but there are also markers or “tags” on the DNA that can turn genes on or off. These tags are known as “above the genome markers” because they can act like a switch to override the recipe our genes give instructions for. For example, these tags can be methylation, acetylation, or many others. Importantly, we can think of these tags as different flavors that can be substituted into the same recipe. It is like having a recipe for strawberry cake but using chocolate instead, changing the final flavor of the cake. As you may imagine, if you were expecting a strawberry cake but got a chocolate cake, you might be pretty disappointed.  

Back to the Science

The effects of short-term social isolation have been studied in songbirds by isolating some female finches in cages overnight5. In general, researchers found social isolation works quickly in the brain to turn off certain genes and is similar to reducing the presence of certain ingredients when baking a yummy cake, or in this case building a healthy brain. This might sound frighteningly similar to what many people across this planet are being forced to experience right now, so let’s take a look at how they came to this conclusion. 

After one night of social isolation, the researchers analyzed the different RNA found in the finches’ brains to see which genes were turned on or off. Essentially, they were looking at different variants of cake and comparing the ingredients used. They found less genes associated with memory, learning, and brain development in the brains of socially isolated finches6. Specifically, there were less of the genes EGR1 and BDNF, which are both needed for healthy brain processes.

However, looking at just one experiment with only female finches still leaves questions unanswered because experiments have their own individual factors that might affect the results. The researchers took it a step further by studying female songbirds from around the globe to see how different environments might affect the results. Their findings matched the changes in EGR1 and BDNF observed in their original study. Replicating results is an essential component of good science and it strengthens the link between social isolation and the observed changes in ingredients. 

In addition, they studied male and female finches under stressful control conditions like new cages in a laboratory setting and found if either sex is housed overnight with another bird of the same sex, then the ingredients making the cake no longer changed. Instead, you get the healthy brains that you were expecting. This is an important scientific concept known as necessary. In science, if something is necessary, then it must be present to cause a certain effect. If it is not present, then the effect will be absent. These tests establish that general stress and geographic location was not sufficient to cause the ingredients to change. Because social isolation is necessary for the ingredients to change, it provides strong evidence that social isolation causes a decrease in the amount of BDNF. 

Then, the next step is to investigate if epigenetics causes the reduction in BDNF. What happens if epigenetic marks like methylation and acetylation cause the flavor of the strawberry cake to change? Simply put, it is like replacing a bunch of the strawberries with chocolate so the strawberry cake no longer tastes right. This is the basic concept of epigenetics, but for a more thorough review on epigenetics, please see the first podcast on neuroepigenetics. They found that social isolation causes methylation of the BDNF gene, and previous work has shown methylation of the BDNF gene changes its level and therefore cognitive ability and brain development. Interestingly they found decreased levels of BDNF even up to 48 hours after one night of social isolation. This implies the effects of social isolation could have long-lasting consequences on our bodies. In other words, lasting changes are similar to rewriting the recipe, reflecting more permanent changes to the DNA. However, more work is needed to see how long these changes actually last.

         The results they found about social isolation in songbirds are important because other researchers have studied social isolation in various animals. Social isolation experiments with mice, rats, and birds have linked social isolation to less BDNF6. Verifying these results in different species is important because it provides greater support when considering these findings in humans. In terms of actual brain function, many of these studies link changes to BDNF in our brains to issues with spatial memory and learning7

  Furthermore, there are other studies on social isolation that associate changes in BDNF with brain damage and more broadly with other neuropsychiatric diseases7. A study on socially isolated rats during early adolescence shows that social isolation causes interruptions to electrical signals in the brains and less of the essential BDNF gene8. This study suggests that changes in BDNF are due to acetylation tags, another type of epigenetic marker. Basically, instead of replacing strawberries with chocolate like in methylation, this time the strawberries were replaced with peanuts, so once again it is not a regular strawberry cake. 

Discussion

Currently, self isolation is a topic that is being faced globally, but the effects of being raised under socially isolating conditions or simply enduring them for a period of time still remain poorly understood. Recently, it has been noted that social isolation and schizophrenia create similar electrical impairments in the brain. Many studies have even shown that social isolation can trigger a myriad of neuropsychiatric diseases, emphasizing the importance of social networks10,11. The implications of social isolation are greater than the expression of a few genes such as BDNF and others that have been identified. Socially isolating environmental conditions may have important effects on human behavior. Epigenetic marks like methylation or acetylation likely change the flavor or type of ingredient used: instead of strawberries, using chocolate or peanuts. 

Understanding social isolation is important because it can increase anxiety, depression, impulsivity, pain sensitivity, cognitive impairment, and addictive behaviors10. Learning how social isolation causes our genes to turn on or off and influences our behavior, might help people cope with this pandemic a bit better, as well as any future instances of social isolation. As authors, we hope reading this has shown you the importance of maintaining your social networks as much as possible despite the current COVID-19 pandemic, stay at home orders, and potential lockdowns many other countries are facing.

Although knowing is part of the battle, many relevant questions regarding social isolation remain unknown. Can virtual contact such as Facetime, Skype, and other video software ease the effects of social isolation? Is there a certain level of social isolation that is related to a physical component of touching another person? What are the long-term effects of social isolation on humans? Are the epigenetic changes resulting from social isolation inheritable? All these questions remain unanswered, but relevant given the expected increase in the number of babies experts are predicting in about 10-12 months, due to people being home all day.

 

Conclusion 

All of us are facing a new reality that could mean we are going to be lonely and sad because of COVID-19. As such, remaining socially connected right now can be especially difficult but is more crucial than ever.

The research has shown that social isolation is related to the amount of BDNF found in brains, which is important because BDNF is essential for healthy brain development and function. Social isolation modifies our recipe and changes the ingredients put into a cake, consequently affecting the final product. Different forms of epigenetic regulation explain how social isolation turns genes on, off, or changes their levels like a dimmer switch. Overall, this can make a person more susceptible to feeling lonely, isolated, anxious, and depressed.

Although we have highlighted the harmful neurologic effects of social isolation, we must emphasize the importance of proper social distancing, isolation, and self-isolation. As such, we encourage everyone to maintain healthy social networks while properly adhering to stay at home orders. Virtual networking has already emerged as a vital way for people to not feel as isolated right now, and we suspect it could help mitigate the negative consequences of social isolation. 

  Please stay physically and mentally healthy as we work together to overcome COVID-19, talk to your friends everyday, and find a positive every morning. There are numerous ways to stay connected– whether it be taking an online workout class with others or virtually watching a show with someone. And finally, we cannot stress this enough, please wash your hands and don’t touch your face.

 

 

References

 

  1.     Zhang, Q. and D. Wang, Assessing the Role of Voluntary Self-Isolation in the Control of Pandemic Influenza Using a Household Epidemic Model. Int J Environ Res Public Health, 2015. 12(8): p. 9750-67.
  2.     Zhang, X., et al., Willingness to Self-Isolate When Facing a Pandemic Risk: Model, Empirical Test, and Policy Recommendations. Int J Environ Res Public Health, 2019. 17(1).
  3.     Freeman, J., et al., “A non-person to the rest of the world”: experiences of social isolation amongst severely impaired people with multiple sclerosis. Disability and Rehabilitation, 2019: p. 1-9.
  4.     Goossens, L., et al., The genetics of loneliness: linking evolutionary theory to genome-wide genetics, epigenetics, and social science. Perspect Psychol Sci, 2015. 10(2): p. 213-26.
  5.     George, J.M., et al., Acute social isolation alters neurogenomic state in songbird forebrain. Proc Natl Acad Sci U S A, 2019.
  6.     Zaletel, I., D. Filipovic, and N. Puskas, Hippocampal BDNF in physiological conditions and social isolation. Rev Neurosci, 2017. 28(6): p. 675-692.
  7.     Han, X., et al., Brief social isolation in early adolescence affects reversal learning and forebrain BDNF expression in adult rats. Brain Res Bull, 2011. 86(3-4): p. 173-8.
  8.     Li, M., et al., Cognitive dysfunction and epigenetic alterations of the BDNF gene are induced by social isolation during early adolescence. Behav Brain Res, 2016. 313: p. 177-183.
  9.     Feinberg, A.P., The Key Role of Epigenetics in Human Disease Prevention and Mitigation. New England Journal of Medicine, 2018. 378(14): p. 1323-1334.
  10.   Famitafreshi, H. and M. Karimian, Social Isolation Rearing Induces Neuropsychiatric Diseases: Updated Overview. Mol Neuropsychiatry, 2019. 4(4): p. 190-195.
  11.   Matsumoto, K., et al., Post-weaning social isolation of mice: A putative animal model of developmental disorders. J Pharmacol Sci, 2019. 141(3): p. 111-118.

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