Retroviruses and schizophrenia: a scientific detective story

Discover has a fascinating article on the scientific detectives working to uncover the causes of schizophrenia, trying to unravel genetic sequences from hundreds of people with schizophrenia, twin studies, a mysterious birth-month effect, and retroviruses that we seem to be born with:

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."

The first, pivotal infection by toxoplasmosis or influenza (and subsequent flaring up of HERV-W) might happen shortly before or after birth. That would explain the birth-month effect: Flu infections happen more often in winter. The initial infection could then set off a lifelong pattern in which later infections reawaken HERV-W, causing more inflammation and eventually symptoms. This process explains why schizophrenics gradually lose brain tissue. It explains why the disease waxes and wanes like a chronic infection. And it could explain why some schizophrenics suffer their first psychosis after a mysterious, monolike illness.

The Insanity Virus

(via Beyond the Beyond)