Your Poor Pandemic Brain

The Pandemic Changed You. It Also Changed Your Brain.

The toll a year of loneliness, stress, fear, trauma, and loss takes on the structure and function of the brain

Animation: Carolyn Figel for Elemental

Sandro Galea, MD, is a physician and epidemiologist who knows trauma: He has studied people’s mental health in the aftermath of, among other earth-shattering events, 9/11, hurricanes, and civil unrest. In March and April 2020, the Boston University School of Public Health dean conducted one of the first mental health surveys of Americans during the Covid-19 pandemic. Galea found that in those early months, depression rates in the United States had more than tripled compared to the years prior, up from 8.5% to 27.8%.

“We were anticipating to find elevated rates, because we know that [depression increases in prevalence] from other large-scale events, but the threefold increase was surprising,” Galea says. “Typically, in general populations after these events, you’d expect about a doubling, so the threefold increase was surprising, no question.”

Anyone who’s lived through the past year could tell you that March and April were not a blip. More recent research indicates that depression rates have remained consistently elevated during the pandemic, ranging between 23.5% and 30.2%, depending on the month. The latest numbers from February place the national average at 27.9%. This data comes from the Household Pulse Survey, a weekly mental health screen of roughly 73,000 Americans conducted by the National Center for Health Statistics and the U.S. Census Bureau that started in April 2020. Visits to hospital emergency departments for suicide attempts and drug overdoses have also spiked, increasing by 6% and 17%, respectively, from 2019 to 2020.

“You’ve lost social contact; you may have lost loved ones; you may have lost your job. All of these things are conspiring to really negatively hit our brain.”

There’s no doubt about it — people are struggling. Just writing that statement feels like the understatement of the year. Of course we are! We’re about to enter year two of a pandemic that has killed more than 500,000 Americans, caused chronic illness in hundreds of thousands more, and resulted in unemployment rates not seen even during the Great Depression. It should come as no surprise that a year of stress, loneliness, fear, and trauma has affected our mental well-being. But has it also affected our brains? Do the increases in psychiatric symptoms correspond to real physiological changes within our 86 billion neurons?

“This is completely uncharted territory,” says James Herman, PhD, a professor of psychiatry and behavioral neuroscience at the University of Cincinnati and director of the Laboratory of Stress Neurobiology. “You’ve lost social contact; you may have lost loved ones; you may have lost your job. All of these things are conspiring to really negatively hit our brain.”

While there have been numerous surveys of people’s mental health over the past year, for obvious logistical reasons, not a lot of research has been done on the neural consequences of the pandemic. This is partly because we’re still in the middle of it, and science takes time. Also, it’s hard to rationalize putting a person into an MRI scanner during shelter-in-place orders. However, we can draw similarities from historical events and previous psychological research about the impact living through a year of a pandemic has taken on our brains.

What chronic stress does to the brain

It’s unclear precisely when “normal” frustration and sadness in response to a hellish year tip into the realm of the pathological. However, the accumulation of stress — enormous, unending stress that we are not evolutionarily equipped to handle — appears to be at the root of most people’s mental health problems right now. Supporting this, the people who are at the highest risk for developing depression and anxiety are those with the most stressors and the fewest resources. This includes people who have lost their jobs or are facing financial insecurity, as well as people who live alone or who have small children. Demographically, younger people, women, Black and Latinx adults, and those without a high school diploma also report higher rates of mental health symptoms during the pandemic.

Other studies have found that nearly one in five people who’ve recovered from Covid-19 are diagnosed with a mental health condition in the months immediately following, including anxiety, post-traumatic stress disorder (PTSD), and depression. Frontline health care workers are another high-risk group, and as many as 40% to 50% report experiencing symptoms of depression and anxiety because of the pandemic. People grieving the loss of a loved one are also at greater risk for a subsequent mood or anxiety disorder.

Stress and the body’s response to it are not inherently bad. In fact, an acute stress response is a good thing; it helps us to survive by raising our cortisol levels and heart rate and changing our body’s use of energy so that we can escape the bear or the tiger or whatever the classic caveman example is. But, crucially, it’s normally a very short response that gets shut off when the threat goes away.

Chronic stress is a different beast, one that can lead to changes in the brain that open the door for psychiatric disorders, particularly depression, anxiety, PTSD, and substance use disorders. Under chronic stress, the adrenal glands are no longer releasing a pulse of cortisol into the bloodstream—it’s a continuous stream. Some of that cortisol passes through the blood-brain barrier and activates glucocorticoid receptors on brain cells. Long-term activation of those receptors can cause profound and lasting changes to the structure and function of brain cells.

One change that occurs is mediated by the brain’s immune system — a family of cells called microglia that are located throughout the brain. Under normal circumstances, one role of microglia is to chop up and clear out damaged or unused synapses — the connections between neurons that enable brain cells to communicate. In small doses, this is a normal part of healthy brain maintenance. During periods of severe stress, however, many more microglia are produced and become activated by the cortisol circulating in the brain. The excess, over-activated microglia can then start to prune out synapses that are still necessary and functional.

“As a consequence, you’ll lose the complexity of your neurons, and if it’s pronounced enough, it can cause a number of negative outcomes,” Herman says. “It can impair memory, it can impair cognitive processing, and it can even impair the ability of the brain to control stress responses. So, in many ways, these types of cellular responses can actually even make the stress worse, almost like in a positive feedback loop.”

Three brain regions that appear to be particularly affected by chronically high cortisol levels and the subsequent culling of synapses are the amygdala, which triggers fear and anxiety responses; the hippocampus, an area important for learning and memory, as well as mood and emotion regulation; and the prefrontal cortex, the brain’s executive center involved in things like future planning and impulse control.

These areas are highly connected by superhighways of synapses and are in constant communication with one another. For example, the amygdala might sound the alarm about a rustle in the bushes. You could jump to the conclusion that a snake’s in there, ready to bite, so you should make a run for it. But the prefrontal cortex quickly evaluates the situation and determines that because you’re walking through Oakland in the middle of February, a snake is highly unlikely. The prefrontal cortex relays this message back to the amygdala and tells it to calm down.

The synapse pruning that occurs during times of chronic stress can disrupt the balance between these brain regions. In anxiety disorders, and PTSD in particular, the prefrontal cortex and the amygdala become less connected, and there is greater than normal activity in the amygdala and less in the prefrontal cortex. As a result, there’s nothing holding the amygdala back from constantly sounding the alarm, so you get more stressed out over more things. The amygdala relays that stress signal to the hypothalamus — the brain’s hormone command center — to start the chain of events to release even more cortisol from the adrenal glands, creating a vicious cycle.

The state of being depressed is itself stressful to the brain. As stress causes people to feel depressed, more cortisol is released, further affecting the nucleus accumbens.

With depression, the prefrontal cortex and the hippocampus are most affected, and both see a loss in volume and function. This happens because the activation of the glucocorticoid receptors in the area prevents new growth in the region. As a result, people with depression have significantly smaller hippocampi than non-depressed people, which is thought to contribute to greater difficulty regulating their mood.

“What happens with stress is that you lose synaptic structure in the prefrontal cortex, and it’s thought that actually removes the brakes on the amygdala, and it allows the amygdala to overdrive,” Herman says. “The amygdala is being told to grow, whereas the hippocampus and the prefrontal cortex have been told to retract. It’s very interesting biology, how you kind of shift the emphasis of the brain toward a mode that is more associated with fear and negative affect.”

The fallout of trauma

Many of the changes that occur in the prefrontal cortex, amygdala, and hippocampus overlap between depression, anxiety, and PTSD. Perhaps unsurprisingly, there is also a lot of comorbidity with these conditions, and many people are diagnosed with both depression and anxiety, for example.

“There is very little specificity to these neural alterations. So you can see it in depressed people, but you can see the same smaller hippocampus, for example, in PTSD and some other forms of anxiety,” says Ian Gotlib, PhD, a professor of psychology at Stanford University. “In our lab, we focus on depression, but I think many of our findings, if we had studied people with anxiety instead, we’d find very similar patterns of brain function.”

Instead, what distinguishes these diagnoses are the symptoms people experience. PTSD, for example, stems from a singularly traumatic event, and so the amygdala’s hyperactive alarm response is especially triggered by stimuli that remind the person of their trauma. The hippocampus — the learning and memory center — is also affected in PTSD, and memory irregularities, including nightmares and flashbacks to the traumatic experience, are common with the disorder.

In the pandemic, people who have been directly affected or have seen firsthand the death and destruction caused by the virus are at a higher risk for developing PTSD. Several studies have shown that as many as one in three people who were hospitalized for Covid-19 have symptoms of PTSD afterward. These numbers are on par with the PTSD rates reported for survivors of the coronaviruses SARS and MERS during and after the outbreaks in 2003 and 2012. Health care workers on the front lines of the pandemic are also at an increased risk of developing PTSD, and surveys of hospital workers have found PTSD symptoms in 17%, 23%, and 29% of doctors and nurses. For context, PTSD rates in the general population are around 7%. That number rises to anywhere from 13% to 30% in groups exposed to significant trauma, like veterans.

“You should expect higher levels of anxiety, depression, and PTSD in those who are specifically exposed to danger or death,” says Yuval Neria, PhD, a professor of medical psychology in the departments of psychiatry and epidemiology at Columbia University Medical Center. “So, frontline workers, health care workers, essential workers who are exposed to higher levels of stress or even traumatic events” are especially at risk.

For people who haven’t witnessed death from Covid-19 firsthand, Neria says the pandemic is not a typical traumatic event, so a diagnosis of PTSD is unlikely. “It’s not time limited; it’s not geographically limited; it’s not culturally limited. It’s all over, and it’s lengthy, and it’s kind of amorphic,” he says. “Usually, traumatic events are very clear where the threat is coming from. Here, the origin of the threat or the nature of the threat is not clear at all. It’s a very different experience altogether.”

But that doesn’t mean the stress of the pandemic hasn’t taken its toll.

Why it’s hard even if you’re “fine”

Even if you’ve been lucky to escape either personal illness or working on the front lines, that doesn’t mean you’re okay. You’re still experiencing tremendous levels of stress just by the nature of living through a year of a pandemic, and that takes a toll on the brain.

For instance, you might be experiencing what journalist Sarah Smith calls “pandemic fine: a state of being in which you are employed and healthy during a pandemic but you’re also tired and depressed and feel like trash all the time.”

All the loss and stress experienced during the pandemic are having an outsized impact on the brain’s reward circuit and our ability to feel pleasure.

A more technical name for this might be anhedonia: an inability to find pleasure in things you used to enjoy. Anhedonia is a hallmark symptom of depression, and it stems from dysfunction in the brain’s reward circuitry. That includes areas like the dopamine-rich nucleus accumbens, which, it turns out, is also negatively affected by chronic stress and elevated cortisol levels.

“What stress can do is it can negatively affect the function of that reward circuit. One of the key symptomatic features of depression, for example, is anhedonia — basically, the failure to find pleasure in things that you previously found to be pleasurable,” Herman says. “That’s a direct interaction between the stress pathways in the brain and the reward pathways. There is evidence for reduced prefrontal interaction with the nucleus accumbens, for example, and differences in dopamine release in the cortex.”

What’s more, the state of being depressed is itself stressful to the brain. As stress causes people to feel depressed, more cortisol is released, further affecting the nucleus accumbens, and the more dysfunctional this region gets, the worse you feel.

“The reward circuitry guides your approach behavior [your motivation or desire for an object that causes you to work for or go toward it], and as it blunts, you stop finding things motivating, appealing, interesting,” Gotlib says. “That builds on itself, and it becomes even more reduced. So there’s this kind of circular [effect happening]: It reduces your approach behavior, and that reduced approach behavior further reduces activation in that circuitry, which further reduces your approach until ultimately, in severe cases, you just can’t get out of bed.”

Herman and Gotlib think all the loss and stress experienced during the pandemic are having an outsized impact on the brain’s reward circuit and our ability to feel pleasure. This can lead not only to depression but also to problems with drug and alcohol use, which activate the reward circuit and which many people use to self-medicate. Supporting this theory, drug and alcohol use have risen during the pandemic, as have drug overdoses.

The unique stress of loneliness

One reason so many people may be turning to drugs and alcohol during the pandemic is that one of our primary, healthier coping mechanisms to ameliorate the negative impacts of stress has been taken from us: social support.

“Humans are a social species,” says Julianne Holt-Lunstad, PhD, a professor of psychology and neuroscience at Brigham Young University. “Our brains have evolved to expect proximity to others. Throughout human history, we’ve had to rely on others for survival, and when we lack proximity to others, particularly trusted others, in essence, our brains have to work harder.”

By stripping us of human connection, the coronavirus has also robbed us of our primary means of accessing support and mitigating the ramifications of the many challenges we’re going through right now. This is true on a larger systems level as well as on a cellular one. Without close proximity to others, the body’s stress response is higher than it might be otherwise. Loneliness and social isolation are also stressful in and of themselves, and they are experienced in the brain as being in a state of general threat, triggering the release of stress hormones.

“All else being equal, when we’re alone, our brain is a little more vigilant for any signs of danger. Also, our brain perceives demands from the world as more demanding than they would be if we had someone with us,” says James Coan, PhD, a professor of psychology at the University of Virginia. “And there’s a really simple reason for it: It’s that the world is more demanding when we’re alone, because anything that the world demands of us when we’re alone, we have to do by ourselves.”

Coan has tested this theory through a set of experiments in which he scans people’s brains while they’re undergoing a stressful experience — receiving a mild electric shock, in this case — both while they’re alone and when they’re holding the hand of a friend or family member. His lab found that parts of the brain’s alert system doesn’t become as active when the person is shocked in the presence of social support.

“When you’re holding someone’s hand who you trust and know and love, your brain seems to see the threat cue differently than it does when you’re by yourself,” Coan says. “And what it sees is a cue that’s just less threatening. So you see less blood flow in the brain going to places that process threat and that are also responsible for regulating your behavior in the context of that threat.”

The area that Coan has focused on in his research is called the dorsal anterior cingulate cortex (dACC), which is involved in self- and situational monitoring and sounds the alarm when the brain needs to take action. Ordinarily, when something unexpected and unpleasant happens, the dACC springs into action to direct blood flow and resources to the prefrontal cortex so the brain can decide how best to respond. When people are holding hands, however, the dACC doesn’t become as activated by the shock and, consequently, neither does the prefrontal cortex. In the presence of social support, something like a shock doesn’t seem as, well, shocking to the brain.

Without this type of social support, the isolation inflicted on us by the pandemic has made the stressors we encounter even worse.

Loneliness and social isolation are also stressful in and of themselves, and they are experienced in the brain as being in a state of general threat, triggering the release of stress hormones.

Moving forward

So, what can be done about all this? And once the pandemic is over, will we all go back to normal, or will the changes in our brains remain, like scars?

The researchers interviewed for this article said that they predict many people will recover on their own once the stressors are relieved, but not everyone will. “My expectation is there will be some recovery,” says Galea, the Boston University public health expert. “The majority of people will resolve spontaneously, but there is a proportion — usually about a third, but that’s really a very [rough] rule of thumb — who will benefit from help.”

Evidence from past pandemics supports this projection, with rates of depression and anxiety declining in the general population but symptoms remaining in a substantial percentage of people, particularly those who experienced greater trauma. For example, one study found that three years after the SARS outbreak, 22.8% of hospital workers still had moderate to severe depression. Aspects of the pandemic that increased people’s odds of lingering depression were having worked directly with SARS patients, having been exposed to the virus themselves and needing to quarantine, and having a history of past trauma.

The good news is that treatment can help, whether it comes in the form of psychotropic medication or talk therapy. And while the source of people’s depression and anxiety symptoms may stem from an unprecedented event, their effect on the brain is not new, and experts know how to treat them.

“From my perspective, depression is depression. And if it starts to interfere with a person’s day-to-day functioning — and if it’s a diagnosis of depression that’s a given, that’s a criterion for the diagnosis — then I think treatment is absolutely warranted,” Gotlib says. “And whether it’s medication or whether it’s some kind of empirically supported therapy like cognitive therapy or interpersonal therapy, it doesn’t matter. Just get some treatment, because we can treat it. We can treat a depressive episode.”

A potentially bigger concern is that even the people who do recover after the pandemic may now be at increased risk for another mental health episode in the future. Roughly three-quarters of people who’ve experienced one depressive episode in their lifetime will have another.

“Obviously, you have a concern in terms of right now, but what’s really more concerning is that now the risk profile in the population is worse than it was before,” Galea says. “So, even if this resolves, which it will resolve for most people—these mood-anxiety disorders that are in the face of acute stressors, they get better — the problem is that now they are at higher risk of other mood-anxiety disorders throughout their life.”

This doesn’t necessarily mean, however, that the pandemic is entirely to blame. Instead, the researchers say that many of the people who are struggling right now likely already had a higher risk of developing a mental health disorder at some point during their lifetime. And if the pandemic hadn’t triggered it, another stressful event might have. In other words, there aren’t necessarily that many more people who are at risk for a future episode now than there were before.

“It’s not that they’re more likely to experience another episode down the road because they were depressed in the pandemic,” Gotlib says. “Having been depressed in the pandemic might be a sign that they were at risk to start with.”

This is not a rosy view for the future, but it doesn’t have to be a fatalistic one. Even prior to 2020, many experts thought the United States was already experiencing a mental health and loneliness crisis. And although the pandemic has undoubtedly made the situation worse, it has also, we can hope, brought this second pandemic out of the shadows and alleviated some of the stigma around it.

My goal in writing this article is not to be a downer or to pathologize a globally traumatic event. My hope is that by laying out some of the very real changes that can take place in the brain, the very real toll that a year of stress and loneliness and loss can take, people may feel a little less abnormal or like they’re failing. What we’ve gone through has been a perfect storm of challenges for our brains, but also, as Gotlib said, depression and anxiety are not unique, and we do have treatments for them. And just as these changes from stress can occur, so can others that promote healing and resilience.

This is the first in a series of articles to mark the one-year anniversary of pandemic life and explore the toll this past year has taken on people’s mental health. Future articles will cover resilience and recovery in the brain.

Health and science writer • PhD in 🧠 • Words in Scientific American, STAT, The Atlantic, The Guardian • Award-winning Covid-19 coverage for Elemental

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