Schizophrenia: caused by retroviruses?

Paul Raven @ 24-11-2010

I remember blogging the toxoplasma-causes-schizophrenia speculation right here back in 2006, and it’s been a hardy perennial on the weird’n’wonderful blog circuit ever since… but as science-fictional as it sounds – pure Invasion-of-the-Bodysnatchers stuff, albeit without the Communist subtext – an increasing number of psychiatrists are starting to conclude that schizophrenia isn’t caused by distant parenting or dodgy genes, but by a virus that we all carry within ourselves [via TechnOcculT]. Just one of many, in fact:

Viruses like influenza or measles kill cells when they infect them. But when retroviruses like HIV infect a cell, they often let the cell live and splice their genes into its DNA. When the cell divides, both of its progeny carry the retrovirus’s genetic code in their DNA.

In the past few years, geneticists have pieced together an account of how Perron’s retrovirus entered our DNA. Sixty million years ago, a lemurlike animal—an early ancestor of humans and monkeys—contracted an infection. It may not have made the lemur ill, but the retrovirus spread into the animal’s testes (or perhaps its ovaries), and once there, it struck the jackpot: It slipped inside one of the rare germ line cells that produce sperm and eggs. When the lemur reproduced, that retrovirus rode into the next generation aboard the lucky sperm and then moved on from generation to generation, nestled in the DNA. “It’s a rare, random event,” says Robert Belshaw, an evolutionary biologist at the University of Oxford in England. “Over the last 100 million years, there have been only maybe 50 times when a retrovirus has gotten into our genome and proliferated.”

But such genetic intrusions stick around a very long time, so humans are chockablock full of these embedded, or endogenous, retroviruses. Our DNA carries dozens of copies of Perron’s virus, now called human endogenous retrovirus W, or HERV-W, at specific addresses on chromosomes 6 and 7.

If our DNA were an airplane carry-on bag (and essentially it is), it would be bursting at the seams. We lug around 100,000 retro­virus sequences inside us; all told, genetic parasites related to viruses account for more than 40 percent of all human DNA. Our body works hard to silence its viral stowaways by tying up those stretches of DNA in tight stacks of proteins, but sometimes they slip out. Now and then endogenous retroviruses switch on and start manufacturing proteins. They assemble themselves like Lego blocks into bulbous retroviral particles, which ooze from the cells producing them.

[…]

Through this research, a rough account is emerging of how HERV-W could trigger diseases like schizophrenia, bipolar disorder, and MS. Although the body works hard to keep its ERVs under tight control, infections around the time of birth destabilize this tense standoff. Scribbled onto the marker board in Yolken’s office is a list of infections that are now known to awaken HERV-W—including herpes, toxoplasma, cytomegalovirus, and a dozen others. The HERV-W viruses that pour into the newborn’s blood and brain fluid during these infections contain proteins that may enrage the infant immune system. White blood cells vomit forth inflammatory molecules called cytokines, attracting more immune cells like riot police to a prison break. The scene turns toxic.

In one experiment, Perron isolated HERV-W virus from people with MS and injected it into mice. The mice became clumsy, then paralyzed, then died of brain hemorrhages. But if Perron depleted the mice of immune cells known as T cells, the animals survived their encounter with HERV-W. It was an extreme experiment, but to Perron it made an important point. Whether people develop MS or schizophrenia may depend on how their immune system responds to HERV-W, he says. In MS the immune system directly attacks and kills brain cells, causing paralysis. In schizophrenia it may be that inflammation damages neurons indirectly by overstimulating them. “The neuron is discharging neurotransmitters, being excited by these inflammatory signals,” Perron says. “This is when you develop hallucinations, delusions, paranoia, and hyper-suicidal tendencies.”

If they’re right, then medicine may be close to discovering a way to head schizophrenia off at the metaphorical pass; having seen first-hand the sudden (and often terrifying) way in which those maladies can destroy the lives of their sufferers (and those close to them), I sincerely hope they are.

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One Response to “Schizophrenia: caused by retroviruses?”

  1. Buffalo says:

    It is a compelling idea though the seasonal variations related to birth month have been known for a long time to be associated with schizophrenia. Usually you hear people talking about “schizophrenias” rather than a single cause “schizophrenia.” I wonder how the retroviral theory could explain issues related to variations in brain ventricle size, microarchitectural changes in brain cell organization, nutritional status of mothers during pregnancy, and the host of other things that have been identified among those that suffer with the condition?