Chickenpox Virus Heightens Risk of Major Depression in Later Life in a 10-year Longitudinal Study


Major depression is arguably the worst disease you can get, for it crushes the soul, so to speak. It's also one of the leading causes of disability and suicide worldwide. 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 viruses comprise part of our environment comprises. Some viruses are capable of invading the brain, causing neurological dysfunction that may underlie clinical depression. 

Over 90% of children have caught Varicella-zoster virus (VZV), which may cause chickenpox (varicella) or no symptoms. Regardless, once infected, VZV enters latency in the peripheral sensory neurons for life and may reactivate decades later to cause shingles (zoster, painful rash). But growing evidence shows that VZV reactivation poses more health consequences than just shingles.

In a 10-year longitudinal, nationwide study in Taiwan, published in 2014, researchers randomly selected one million people from the population. After excluding those with a history of psychiatric disorder, the study identified 1,888 individuals diagnosed with herpes zoster, which were matched to 7,552 uninfected controls (randomly chosen). Random selection ensures that the sample is representative of the general population.

Results showed that individuals diagnosed with herpes zoster had a higher incidence of major depression (2.2% vs. 1.4%) or any depressive disorder (4.3% vs. 3.2%) compared to uninfected controls. Such differences were statistically significant, equating to increased risks of 49% and 32%, respectively, after accounting for potential confounders (e.g., age of diagnosis, sex, income, comorbidities, etc.)

The study authors believed that their findings may be explained by defective VZV immunity. Prior studies have reported lower VZV-specific T cell immunity in people with major depression than those without. (VZV is mainly controlled by T-cells).

Poorly controlled VZV or shingles is known to damage nerve cells and cause postherpetic neuralgia, a type of chronic pain. In rare cases, encephalitis (brain inflammation) may even occur after shingles. In laboratory settings, VZV has been shown to infect neurons (Figure 1) and blood vessels in the brain, resulting in the secretion of inflammatory cytokines that may harm brain cells.

Figure 1. Immunostaining of neurons infected with varicella-zoster virus (VZV) engineered to express a green fluorescent protein (GFP). Thus, green staining indicates VZV infection, whereas red staining indicates neuronal staining. Panel G is low magnification, whereas panel H is high magnification. And panel H reveals that most neurons have already been infected with VZV at 3–7 days post-infection.
So, it’s not far-fetched for multiple VZV reactivations throughout life to induce subclinical brain inflammation. And major depression is closely tied, in a causal manner, to brain neuroinflammation.

To add another layer of complexity, having viruses in the brain does not necessarily mean they will cause harm, provided the immune system is robust and actively suppresses the virus.

In this way, ensuring a healthy immune system may be our best bet in not letting potentially depression-inducing viruses take over our minds. This also shows that major depression is as much biological as it is psychological and should be treated as such, without stigmatization.

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MSc Biology | 8x first-author academic papers | 280+ articles on coronavirus | Independent science writer


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