Epstein-Barr Virus is a Risk Factor for Major Depression, Longitudinal Nationwide Study Finds

Electron microscopic image of two Epstein Barr Virus virions.Photo byWikipedia Commons.

As one of the leading causes of disability and suicide worldwide, major depression is arguably the worst disease you can get, for it crushes the soul, so to speak.

Major depression, clinically known as major depressive disorder (MDD), refers to depressive symptoms severe enough to impair daily activities. It’s different from sadness or loosely used depression as an expression of sadness.

A variety of factors cause or contribute to major depression, ranging from environmental, genetic, and lifestyle factors. And our environment comprises viruses, some of which are capable of invading the brain, causing neurological dysfunction that may underlie clinical depression.

A backdrop on Epstein-Barr virus (EBV)

Over 90% of the population worldwide has been infected with Epstein-Barr virus (EBV) at some point in their lives, especially during childhood, mainly via the oral route such as kissing and sharing eating utensils or food and drinks.

The first EBV infection can either cause a disease typical of common childhood illnesses or no disease. In either case, EBV will establish a latent state in B-cells in the body forever. In this state, EBV may occasionally reactivate and re-infect cells, which may or may not cause disease again.

While most cases of EBV infection are symptomless, it can cause infectious mononucleosis in some individuals, with symptoms of fatigue, body aches, fever, sore throat, swollen lymph nodes, or rash.

Nationwide study links symptomatic EBV to depression

A 2021 nationwide study in Denmark tracked all 1,440,590 singletons who were born between 1977–2005 up to 2016. During this period, 12,510 of them had hospital contact for infectious mononucleosis.

And these EBV-infected individuals had a 40% higher risk of major depression in later life compared to those uninfected, which remained statistically significant even after five years after EBV infection.

These risk percentages were adjusted for age, sex, birthweight, maternal educational level, and other potential confounders, thus supporting EBV disease as an independent risk factor for major depression.

Although prior studies also found EBV to be related to major depression, they all had low sample sizes. For example, a 2014 meta-analysis calculated a 99% higher prevalence of EBV infection in people with major depression than in healthy people from a total of four studies, totaling only 221 depressed and 252 healthy cases.

So, the 2021 Danish study is the first large-scale study to deliver convincing evidence that prior EBV disease is a risk factor for major depression.

Mechanisms linking EBV to depression

The mechanism by which EBV contributes to major depression is not exactly clear, but scientists suspect that it’s immunological dysfunction.

EBV is known to establish latency (dormant state) in B-cells and may reactivate periodically. EBV has also been found to prime B-cells to secrete auto-reactive antibodies that attack the neuronal myelin sheath, causing multiple sclerosis. But apparently, the defective myelin sheath is also a key pathophysiological aspect of major depression.

Therefore, it is highly probable that multiple reactivations of EBV throughout life, especially in those with weaker immune systems to control EBV reactivation, would gradually damage neuronal myelin sheath in the brain, increasing the risk of major depression.

The Need for Effective EBV Treatments

Unfortunately, no specific vaccines or antivirals have been approved for treating EBV. Only general anti-pain or anti-fever medications, as well as adequate rest and hydration, are recommended to treat EBV infection. By now, we should have one or two approved EBV antivirals. But judging from the lack of it, it’s fair to say we have neglected the threat of EBV for too long.