How COVID lockdowns messed with brains, increasing anxiety, depression

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Israeli neuroscientist Alon Chen can change the mood, the “mental state” of an animal. “We can make a mouse more or less anxious, more or less depressed-like, by changing the activity of specific brain areas or nerve cells,” says Chen, president of the Weizmann Institute of Science.

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COVID has also manipulated human brains, not as much through any direct effects of the virus, but, Chen suspects, through the emotional toll three years of living with the pathogen has taken. Chen was in Toronto recently to raise awareness and philanthropic support for the Weizmann Institute, where scientists recently succeeded in growing synthetic mouse embryos using stem cells taken from skin, and not eggs and sperm.

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In an interview with the National Post’s Sharon Kirkey, Chen talked about why the human brain remains an enigma, what happens to our brains when exposed to a chronic stressor like COVID and why the need for better treatments for anxiety and depression is “immense.” His comments have been edited for length and clarity.

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Q: It’s winter three of COVID. How has living through this pandemic affected our mental states?

A: Just look at the number of people, all the way from very young kids and adolescents to more elderly people. You can see a dramatic increase in mental-health cases, from suicidal ideation all the way to suicide attempts. Mental-health institutions are now so crowded. It’s reported again and again, in western societies and all over Europe and in the U.S. and in Israel, there is quite a clear consensus of this effect.

In the early stages, between the first and second peak, my own group assessed 10,000 adults and asked them multiple questions about their mental state, particularly their stress levels, while at the same time collecting more physiological data, whether they were sick, or not sick, fevers or no fevers. The age group that was most affected was young adults, 20 to 30, rather than the more elderly. They were the ones so heavily dependent on social interactions. The first ones to lose jobs. They were students. Females were more affected than males.

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We didn’t include kids and adolescents, but a lot of studies coming out, even one very recently from Stanford (which suggested pandemic shutdowns physically aged adolescent brains) are showing really dramatic effects on the mental health of young individuals. This is attributed mainly to lack of social interaction.

Mental health strongly depends on environmental stimuli. When you ask why someone develops depression or anxiety or any other mental illness and another person doesn’t, there is a consensus in the field that it’s a combination of genetics, or genetic predispositions — people carry this sensitivity, this vulnerability to develop a disease — but you also need the right environmental exposure, environmental challenge. And environment is everything you drink, smoke, breathe. Stress is the most important or studied environmental factor. And this pandemic was a major, major environmental challenge.

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Q: How does the brain respond to stressful stimuli like a pandemic?

A: It’s something which is embedded within us as a very basic response. The stress response has been conserved through evolution — from fish to humans, these are the same genes, proteins and brain circuits that regulate this response. And it’s a vibrant response. It’s a healthy response. It’s okay to respond this way when you have a challenge. The collective aim of this response is to allow you to cope with this challenge, to survive this threat. Your heart rate will increase, your blood pressure will increase, your blood glucose and your cortisol levels will go up. This is just in the periphery, the rest of your body. But also, within your brain, your level of fear and anxiety will increase. Your cognition, your memory is going to change; your attention, your appetite is going to change. Almost every major brain area will respond to this challenge.

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Is it normal and healthy to respond like this? Yes, it’s healthy and normal because this is a survival response. If the threat is not there anymore, the system must switch off the response and bring all systems back to this original steady state.

With a pandemic, these physiological and behavioural changes are chronically elevated. Anxiety, depression, eating disorders — most psychopathologies have a very strong link with chronic stress. Metabolic related disorders as well, such as metabolic syndrome, Type 2 diabetes, heart and immune related disorders.

Q: Why don’t we understand the biological underpinnings of anxiety and depression?

A: These types of diseases aren’t caused by a change in a specific gene, but many, many genes, and interactions between those genes. We do not understand yet the so-called “signature.” We cannot sequence your DNA and say you have a DNA which puts you at risk to developing anxiety. We have a selected number of genes that we know are associated with anxiety or depression but it’s not that we have a fingerprint, yet, of such a genome. The genetics is very complex, although we know all these diseases have a genetic component. We can see depression in the family, we can see anxiety in the family, we can see schizophrenia. This is one part of it.

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The second part is environment. Let’s take stress. Stress can affect you when you’re an adult, a teenager, a baby, even as an embryo. (Pregnant women) can transmit some signals to the developing embryo.

We have a real problem with even defining (anxiety or depression) itself. It’s not as if we have a blood test, a biomarker, that says you have anxiety type 3, or type 4 or 5. All the diagnostics are done by questionnaires. We don’t have any quantitative biological measures today to define someone as having a mental illness. Think about it. We do not have the same tools to identify the most appropriate treatment, as we do for cancer, for instance. Oncologists can choose the best chemotherapy by sequencing the tumor, or doing histology, or sectioning of the tumour. With depression and anxiety, we don’t have any way to predict side effects. Today, unfortunately, with medication for depression and anxiety, there is still a large percentage of people who do not respond to anything. And the number of side effects and severity of side effects are quite immense.

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These are the last frontiers in biomedical research. They are the most complicated pathologies that exist.

Q: Are we close at all to any kind of biological markers of depression or other mental illnesses?

A: The last decade in neuroscience has been amazing. The field is booming. Today we have technologies that allow us to do things we couldn’t do 10 years ago, from the ability to do genetics at a very high level to the ability to use light to change the activity of nerve cells, allowing us to ask, “Okay, what’s the role of those nerve cells?” There are exciting new treatments and approaches in the pipeline. Today we are still using medications that have very similar concepts to the same ones we used 50 or 60 years ago. The medical need is immense. We need new solutions. And new solutions will come, but only with better understanding not only of the pathological brain, but the healthy brain.

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Q: You said that about 35 per cent of people with depression don’t respond to any type of treatments after a year of trying different drugs. You’re studying ketamine. Why is it promising?

A: Ketamine is used for exactly those 35 per cent of people who do not respond to any available drug. The one approved now (in Canada and other jurisdictions) is a nasal spray. There are advantages and disadvantages. Again, we don’t fully understand how this works. The biggest advantage of ketamine is the fast-acting effect. The kick-in of an SSRI (serotonin selective reuptake inhibitor, a class of drugs taken by millions of Canadians) is between three to eight weeks, which just isn’t good enough for someone who has a severe depression and he or she is having suicidal thoughts and plans right now.

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The big advantage of ketamine is that you can see the effect within half an hour, from what I’ve read and from what my psychiatrist colleagues have told me. There are side effects and it’s not heavily used yet by psychiatrists around the world. But it’s a new, refreshing solution. After 60 years finally we have something that is using a different type of approach.

The problem is that there will probably never be a treatment or drug that is going to work on large percentages of the population. Your depression and my depression, the underlying mechanisms could be totally different. It’s extremely complex. You also must remember there’s a huge diversity — there are some people who are depressed and it’s hard for them to wake up in the morning and go to work, but they do it. They learn and they know how to cope. But other people cannot.

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Q: What about non-drug, non-pharmaceutical interventions?

A: There are approaches which are proven to help for many people, like physical activity. It’s considered the most beneficial way to cope. You don’t need to be an Ironman or an Ironwoman. Just do more than you usually do. We know that exercise generates the development of new brain cells in areas which are very relevant to emotions — the same areas which are affected by antidepressants when they are working.

There’s more and more evidence about meditation or mindfulness. And anything involving enrichment. Like social interactions. Going back to what we said regarding COVID. We’re extremely social organisms, humans. We need interaction with people. I remember my mom during this pandemic. She’s 83. The fact she couldn’t hug her grandkids — I saw how she declined. It was so clear. We need this. As much as you can, enrich your lives with any type of thing that makes you happy and engaged with the world. I love sea kayaking, not just for the sport. For the whole experience. Some people like to work in the garden or go fishing. Anything that causes you to feel good is a fantastic way to cope, to reduce stress levels and help prevent or reduce stress-related pathologies.

National Post