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Depression

Inflammation: A Link Between COVID-19 and Depression?

Connecting policy, infection and immunity with depression.

Key points

  • Inflammation may represent a central pathway connecting the COVID-19 pandemic and depression.
  • Unhealthy diet, less exercise, and higher stress may activate the same depression pathways in the brain as infection with the virus.
  • Lifestyle interventions to help lower inflammation may represent a way to help offset COVID-19-related depression
 Adrian Swancar/Unsplash
Source: Adrian Swancar/Unsplash

As the COVID-19 pandemic rages on, reports of a tax on global mental health are increasingly reported. This toll has been linked to acute and long-term effects of infection (the latter variably described as long-COVID, long-haul COVID and post-acute COVID). Additionally, worsened mental health has been associated with the detrimental effects of policies designed to limit viral spread. One way these seemingly disparate events connect to similar outcomes may be the link between the immune system and mental health. This may be especially important as it relates to depression, as summarized in a recent review article called "Immunological Interfaces: The COVID-19 Pandemic and Depression."

Long before COVID-19 sunk its teeth into our collective wellbeing, depression was already an international concern affecting upward of 300 million people. And while depression is a psychological state, it’s well understood to have biological underpinnings. There are several molecular pathways implicated in depression including alterations in neurotransmitters like serotonin and deficits in neuroplasticity. However, much attention is now focused on the role of the immune system in prevention, development and treatment of depression. More specifically, research suggests an immune state characterized by elevated inflammation may confer a significant risk for depression.

Inflammation has a long rap sheet already, being lambasted for its role in variety of diseases ranging from heart attacks to diabetes. But it is now understood that prolonged or excessive inflammation may additionally compromise brain health. This helps explain growing links between inflammation and worse cognition as well as the aforementioned connection to depression. Here’s a key point: while we often think about inflammation as resulting from an acute injury or an infection (like a twisted ankle or infected wound), a sizable chunk of today’s inflammation is the result of unhealthy food, not exercising and too much unhealthy stress.

So how does all of this connect to the COVID-19 pandemic? Certainly, infection with the virus has been strongly linked to inflammation. Early in the pandemic, worse outcomes were correlated with higher levels of inflammation. Medical publications even described a “cytokine storm,” a deadly reaction to COVID-19 characterized by an acute elevation in inflammation. Some data have also suggested that hospitalized COVID-19 patients have high rates of depression that correlate with their inflammation. Yet now we’re seeing that other factors related to the pandemic are also important in the inflammation-depression equation.

Long after the initial symptoms of COVID-19, and months after a person is no longer considered infectious, thousands of people have described significant residual effects on their health. This syndrome has been called “long COVID,” and is characterized by a wide range of brain-related symptoms including fatigue, brain fog and depression. While the specific causes of long COVID are under active study, inflammatory damage to the body and brain has been proposed as a contributor.

Previous research showed that severe infection with a coronavirus (MERS and SARS) predicted high rates of depressive symptoms on admission to the hospital, as well as in the months to years later. However, even though some data suggest similarly elevated rates of post-hospitalization psychiatric distress in COVID-19 Long COVID remains poorly understood, helping explain why organizations like the NIH have committed over a billion dollars to further investigate the subject.

It seems rather straightforward to make the connection between infection and immune dysfunction (in this case, unhealthy inflammation). But it may be equally relevant to understand how policies enacted to slow spread of COVID-19 may heighten an inflammatory state. Around the world, people have been admonished to remain indoors and isolated. Unfortunately, these can become variables on the wrong side of the inflammation and therefore depressive equation.

Several lifestyle changes in the COVID-19 era may confer higher risk for inflammation. The increase in unhealthy food consumption may predispose to inflammatory metabolic dysfunction that may increase depressive symptoms. An increase in sedentary behavior as a result of the pandemic (now documented across the world) is also linked to more inflammation, as well as higher rates of pandemic-associated depression. Finally general psychological stress related to the pandemic (in part due to excessive news exposure) may meaningfully increase both inflammation and depression.

The takeaway message is simple: inflammation may be a unifying mechanism connecting the infectious and non-infectious effects of the COVID-19 pandemic with depression. So what can we do about it? At a very basic level, we could consider strategies to mitigate excessive inflammation. In addition to avoiding risk for infection, these could include efforts to increase physical activity, improve diet and decrease psychological stress. Supporting access to the outdoors whenever possible could decrease sedentary behavior, provide a needed break from psychologically damaging news and promote access to nature’s stress-relieving effects. Similarly, policies (in our homes or larger scale) designed to promote accessibly and consumption of healthful foods could have anti-inflammatory and therefore anti-depressive effects.

The effects of the COVID-19 pandemic aren’t going away for the foreseeable future. Research will continue to uncover exactly how this monumental event has changed the world, including the state of our mental health. Yet there may be significant harm in waiting to act until all the fallout has been tabulated. We know our mental health is at risk, and increasingly understand the role of inflammation in the process. As we continue to weather the storm of COVID-19, we may benefit from more widespread anti-inflammatory interventions and policy to protect mental health today and for the future.

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