How Does COVID Affect Mental Health?

Recently publicized reports of paranoia, depression, and even suicide among some COVID-19 survivors have come as no surprise to Maura Boldrini, MD, PhD, a neuroscientist and psychiatrist at Columbia University Vagelos College of Physicians and Surgeons.

Throughout her career, Boldrini has investigated the neurobiological changes in the brain associated with cognitive and behavioral symptoms—including suicidal behavior.

“In psychiatry, we have been interested in understanding the role of neuroinflammation in psychosis, depression, and other mental health conditions,” says Boldrini.

“Previously, our group has found increased inflammation in the brains of people who die by suicide. And we’re  now investigating if COVID-related inflammation can trigger suicidal thinking and other psychiatric effects.”

Boldrini and colleagues were recently asked by JAMA Psychiatry to review what’s known about COVID from a psychiatric perspective and suggest possible causes of neuropsychiatric symptoms and potential treatments.

The CUIMC newsroom spoke with Boldrini to learn more.

Why look at the connection between COVID-19 and mental health?

Boldrini: I do weekend shifts at the hospital for our psychiatry consult service, and I have seen COVID-19 patients with new-onset delusions, hallucinations, anxiety, and depression. There have been more than 130 million COVID cases worldwide, so it’s more important than ever to understand how this disease may affect the brain and behavior.

We know that things like isolation, financial burden, and increased drug use due to the pandemic may cause anxiety and depression. But we also think that biological changes like inflammation are linked to our behavior and may provide another explanation for how infectious diseases can affect mental health.

Focusing on the neurobiological changes linked to psychiatric symptoms and behavior could also help to destigmatize mental health conditions and potentially lead to better treatments.

How can a virus cause depression and other psychiatric effects?

We’ve known for a long time that there’s a link between viral infections and mental health. We think that neuropsychiatric symptoms may be caused by the body’s immune response to viruses and other pathogens, triggering the release of cytokines systemically and locally, in areas of the brain involved in depression and other psychiatric conditions, rather than the direct effects of the pathogen.

Increased cytokines can disrupt the production of necessary chemicals (neurotransmitters) that brain cells (neurons) use to talk to each other—which results in our normal behavioral and emotional responses to our living environment.

Moreover, some aberrant chemicals arising from inflammation can make neurons die. When neurons do not adequately communicate with each other, or are lost, cognition, emotions, and behavior can be altered.

Could this be happening in some people with COVID-19?

Our review suggests that COVID’s effects on the brain may be caused by small blood clots and inflammation, which also potentiate each other. The interaction between clots and inflammation in COVID resembles what we see in traumatic brain injury in football players, for example. People with traumatic brain injury may suddenly experience personality changes, sometimes becoming aggressive or suicidal.

The mechanical shaking that causes traumatic brain injury is different from the coagulation and inflammation that occurs in COVID, but both can ultimately cause brain damage due to little strokes and inflammation.

Based on what we know about COVID so far, systemic inflammation may unleash chemicals that trigger symptoms such as hallucinations, anxiety, depression, and suicidal thinking, depending on which part of the brain is affected.

We don’t think that the virus is directly invading the neurons, or other cells, in the brain. Based on an extensive search by Columbia pathologists and other groups, we’ve learned that very little of the virus actually reaches the brain because of a layer of protective cells known as the blood-brain barrier.

But there is evidence that a small amount of virus may be able to enter the brainstem and cerebellum via circumventricular organs—openings in the blood-brain barrier that allow us to sense and respond to toxins. In fact, the little amount of virus that’s been detected in the brain has been found in these regions, which happen to be located near circumventricular organs.

There are other types of infections, such as strep throat, that can enter the brainstem through these openings and cause chronic infection. These infections have been linked to neuropsychiatric symptoms such as obsessive-compulsive disorder and tics.

What kinds of studies need to be done now?

Currently, we are analyzing the electronic health records of deceased COVID patients who had neuropsychiatric symptoms. In my lab, we’re analyzing the brain tissue in greater detail to look for cells and molecules that may be involved in these pathogenic pathways. We’re measuring the amount of microglia, neuronal damage, and inflammatory markers that are present in the brains of these patients.

If we find that inflammation is causing psychiatric symptoms in COVID patients, we would think of approaches to modulate the inflammatory markers and prevent brain damage, slowing down a persistent inflammatory response that is not useful. The approach is similar to how we use drugs to dampen immune response in people with autoimmune disorders, where a prolonged inflammatory response damages the organs.

Another approach would be to use PET to identify inflammation in patients with post-COVID neuropsychiatric sequelae. We are currently doing that in people who have attempted suicide.

I think psychiatry researchers could play an important role in helping uncover the biological effects of COVID on the brain, even in people who did not have severe respiratory symptoms. If we don’t do this work, we could be dealing with a mental health pandemic long after the COVID-19 pandemic is over.

Maura Boldrini, MD, PhD, is associate professor of psychiatry and director of the human neurobiology laboratory at Columbia University Vagelos College of Physicians and Surgeons.

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