Could depression be the result of a brain infection?
"Depression should be re-defined as an infectious disease … argues one scientist," the Mail Online reports.
The news comes from an intriguing opinion piece by an American academic, which argues the symptoms of depression may be caused by infection.
But, as the author of the paper says, his hypothesis is purely "speculative".
It's fair to say feelings of depression can follow some illnesses such as flu, but this is not the same as saying it is caused by infection. And, as this is an opinion piece, the author may have cherry-picked certain articles in support of his hypothesis.
That said, the author does provide some interesting examples of how an infection can lead to a change in mood and emotion.
Infection with the T. gondii strain of bacteria can cause rats to become fearless around cats, a natural predator for these animals.
And a study we looked at in 2012 suggested people who owned cats had a higher risk of suicide, as their pets could make them vulnerable to a Toxoplasma gondii (T. gondii) infection.
Despite the lack of any hard evidence, it is an interesting hypothesis that arguably deserves further investigation, especially given the considerable burden depression places on many people.
Who wrote this piece?
The article was written by Dr Turhan Canli of the department of Psychology at Stony Brook University, New York.
It was published in the peer-reviewed journal Biology of Mood and Anxiety Disorders.
The piece has been published on an open access basis, so it is free to read online.
There is no information about external funding, though the author declared no conflicts of interest.
What are the main arguments?
Dr Canli argues that despite decades of research, major depressive disorder (MDD) remains among the most common mental health conditions.
He argues the illness often recurs, regardless of treatment with antidepressants, and states it is time for "an entirely different approach".
Instead of seeing MDD as an emotional disorder, it should be reconceptualised as a form of infectious disease, he says.
Canli says future research should conduct a "concerted search" for parasites, bacteria or viruses that may play a role in causing depression to develop.
The paper presents a series of arguments in favour of this theory.
Inflammatory markers
- patients with MDD exhibit "sickness behaviour" – they experience loss of energy, have difficulty getting out of bed, and lose interest in the world around them
- studies of inflammatory biomarkers in major depression "strongly suggest an illness-related origin" – inflammatory biomarkers are chemicals in the blood that may indicate inflammation in the body
- these inflammatory markers may represent activation of the immune system in response to some kind of pathogen, which could be a parasite, bacterium or virus
- the author admits there is no direct evidence that major depression is caused by such organisms, but says such a process is conceivable
Examples from nature
There are existing examples of how parasites, bacteria or viruses can affect human behaviour:
- for example, T. gondii, which lives in cats' intestines, lays eggs that are dispersed into the environment on excretion
- when a rat is infected with these eggs, it becomes attracted to the scent of cat urine
- the rat's loss of fear may be caused by parasitic cysts in the rodent's brain affecting levels of various chemicals
- one-third of the world's population are believed to be infected with T. gondii, and infection is associated with inflammatory markers similar to those found in depressed patients
- research has identified a link between T. gondii and national suicide rates, major depression and bipolar disorder
The paper argues bacteria could be another cause of depression, with rodent studies showing a link between various bacteria and levels of emotional stress.
In humans, there is data to suggest bacteria in the gut may contribute to major depression – a controversial suggestion known as "leaky gut theory".
Viruses are the third possible cause of MDD, the author states. One meta-analysis of 28 studies, which examined the link between infectious agents and depression, found viruses that had significant links included herpes simplex, varicella zoster (which causes chickenpox and shingles), Epstein-Barr and Borna disease virus.
Genes
The author says reconceptualising major depression as being causally linked to parasites, bacteria or viruses is useful when thinking about the genetics of the illness.
Perhaps the reason the search for specific genes related to depression has "come up empty" is because scientists have been looking for the wrong organism.
Researchers have been looking for internal changes in human genes that might explain depression, but 8% of the human genome is based on external changes from retroviruses.
Dr Canli goes on to portray the human body as an ecosystem that acts as host to "numerous micro-organisms" that may be passed across generations and could be linked to the risk of depression.
He concludes by suggesting unknown pathogens play a causal role in depression by altering the immune response. He speculates there may even be a class of pathogens that share common modes of action targeting the nervous system.
Such pathogens may work together with other factors, Canli argues. For example, some people may have a latent infection, but depressive symptoms may only emerge after the pathogen is activated by a stressful life event.
Large-scale studies of depressed patients and healthy controls are needed to look at the potential role of pathogens in the development of depression. Such efforts might represent the first step towards developing a vaccination for major depression.
What is the evidence?
The author quotes a variety of sources to support his hypothesis. Many are rodent studies, and others are laboratory studies looking at levels of certain inflammatory biomarkers in depressed and healthy patients, for example.
But this is not a systematic review of the evidence. The author has not carefully searched all the literature on the topic, assessed its quality, and come to a conclusion. He may have cherry-picked studies that might support his hypothesis while ignoring studies that don't.
How accurate is the reporting?
The Mail Online gave the paper's arguments considerable prominence in an article that was accurate but uncritical. Independent expert opinion was not included to balance the argument.
The New York Times took a more discursive approach based on an interview with the author. The item was part of a longer discussion with various experts.
Conclusion
The paper's hypothesis is interesting, but it remains just that – a hypothesis. While it is true that some pathogens, such as the Borna disease virus mentioned in the article, have been linked with neuropsychiatric disorders, there is no proof as yet that bacteria, viruses or parasites could cause major depression.
Still, as the old truism goes: "Absence of evidence is not the same as evidence of absence". The lack of evidence could be because nobody has bothered to look for it before.
The author concludes that, "It would be worthwhile to conduct large-scale studies of carefully characterised depressed patients and healthy controls using gold-standard clinical and infectious disease-related study protocols." This seems to be a reasonable and sensible suggestion.
