All viruses are sly and enigmatic, as cunning as a con artist in their search for a host, insidious in their damage, invisible. SARS CoV-2 doubled the mystery—where had it come from?—then compounded it by behaving in ways that threw us off base. A virus with both respiratory and GI symptoms? One that knocked your sense of smell and caused a fatigue that could last for months?
The most urgent mystery of all is why it hit some of us so hard, while others snuffled and groused and then went on with their lives. The elderly, those without trusted health care, those with compromised immune systems, obesity, diabetes, heart and lung problems—those categories at least made sense. But why target people with mental illness?
The first guess was the obvious one: in this society, they often wind up living without support and access to care. Also, smoking eases symptoms and some psychiatric medications cause weight gain, so they might be less fit in an actuarial sense. And their lives are harder, filled with stress and stigma.
But there is a more startling reason. Researchers found that people with schizophrenia had two and a half times the average risk of dying from COVID-19, even after controlling for other risk factors as well as age, sex, and race. Meta-studies consistently show worse COVID-19 outcomes among people with depression, bipolar disorder, and schizophrenia. “There’s a physiologic vulnerability,” says Charles Raison, a psychiatrist and researcher at the University of Wisconsin-Madison.
The likely cause? Many people with mental illness live with higher levels of inflammation in their bodies. That kind of chronic inflammation wears on the heart and can cause an overreaction to a virus, producing more inflammation, which can then affect the brain.
That has implications for all of us. Teodor Postolache, professor of psychiatry at the University of Maryland School of Medicine, suggests that between one-third and half of people with a serious COVID infection will experience some effect on their mental health, whether it is anxiety, depression, or something more vague, such as fatigue, insomnia, problems concentrating, or “a general sense of not being at your best.” How long those effects last will vary, as does their cause.
A virus can affect the brain and nervous system directly, invading and killing, for example, some of the brain cells that control respiration. But it can also take an indirect route, causing inflammation that, if it rages too long and too hard, can become toxic. Inflammation in the brain can strip nerve cells of their protective coating. Inflammation and stress can break down the barrier between blood and brain, making it easier for cytokines to cross that barrier and intensify neuropsychiatric symptoms. Immune cells can stay infected with CoV long after symptoms of the illness vanish. (If that sounds implausible, consider our feces, which still contain shedded bits of COVID five weeks after infection.
Many years ago, a psychiatrist told me the latest thinking was that schizophrenia could be caused by a virus the person’s mother contracts while pregnant. He called it an “insult” suffered by the developing fetus. The word intrigued me; it felt accurate. Insults are hurled at us as we move through life, unearned and uncalled for, and often leave some damage behind. Still, to my unscientific mind, the theory also sounded bizarre, like blaming demonic possession or a full moon.
Now, paging through the literature, I find plenty of support for the theory that viruses, contracted in utero or even throughout childhood, as the brain continues to develop, can set a genetic predisposition into motion. Viruses can also play a role in bipolar disorder, clinical depression, autism, auto-immune diseases….the list is long. And viruses contracted in adulthood can later cause auto-immune disorders—like the rheumatoid arthritis my mom developed a decade after surviving Legionnaire’s disease.
A quick caveat: viruses have these effects in a small subset of people. These conditions are complex and often have multiple possible causes. Depression itself is probably many different disorders that have the same symptoms, and autism take wildly different forms. The diagnostic labels are a bit like saying you have “dermatitis,” meaning something’s wrong with your skin.
But consider: babies born seropositive for bacterial and viral agents are at “a significantly elevated risk of developing schizophrenia . . . recent findings suggest that the maternal inflammatory response may be associated with fetal brain injury.”
Testing positive for a human CoVstrain, HCoV-NL63, has been associated with a history of mood disorder.
A Danish study looked at the medical records of more than three million people and found that those who had been hospitalized for infection had a 62 percent higher risk of later developing a mood disorder. The more infections a person had, the greater their risk of mental illness later in life. And a past history of an autoimmune disorder increased the risk of a future mood disorder by 45 percent.
The immune system can overdo it.
And the immune system is far more intricately bound up with the brain than we once thought. Researchers at the University of Virginia have just identified a network of vessels that creates a direct connection between the immune system and the brain. That could help explain how stress of any kind—sleep deprivation, abuse, grief—can throw our immune system into high gear, keeping it pumping out powerful stress hormones for months or years, damaging both mind and body.
We will never know what the Plague of Milan did to mental health. But we do know that Parkinson’s disease and encephalitis lethargica, an inflammatory disorder of the central nervous system, both increased at the time of the Spanish flu. And during the recent H1N1, SARS-CoV-1, and MERS-CoV outbreaks, there were reports of increased seizures, encephalitis, and Guillain-Barré. Survivors of SARS-CoV-1 were diagnosed with depression, panic disorder, and obsessive-compulsive disorder at dramatically higher rates (39 percent, 32.5 percent, and 15.6 percent respectively) up to four years after infection, compared to their 3 percent prevalence of any psychiatric diagnosis before infection.
After COVID-19, a Lancet study found patients twice as likely to develop a psychiatric illness for the first time, compared to a control group of people who were sick with the flu.
“The delayed or chronic effects of this pandemic, particularly on public mental health, will not be fully appreciated for several years,” note researchers in Brain, Behavior, and Immunity.
Understanding all this interplay, though, can drive home how physical mental illness is. The symptoms of depression, psychologists point out, are a lot like the symptoms of a bad cold or flu: You are tired, you lose your appetite, you shudder at the thought of getting out of bed. Life is as bland as a bowl of plain oatmeal, with no savor or interest. Future obligations seem overwhelming. That is the immune system at work, creating all those symptoms. And it may play a role in some cases of depression as well.
One clear takeaway? Vaccinating against known and emerging viruses could help prevent some mental illnesses and autoimmune disorders. So many parents have shunned vaccinations in the (disproven) belief that they might cause autism spectrum disorders—but it looks as though the real danger could lie in the inflammation that will be caused by what you are vaccinating against.
Read more by Jeannette Cooperman here.