Each year more 1 in 4 adults in the U.S. suffers from a diagnosable mental illness, and American parents report that nearly 5% of their children – 2.7 million kids -- have a severe emotional or behavioral disorder. Could infectious disease help explain what’s going on?

by Janet A. Ginsburg

“Psychiatry has made great strides in helping kids manage mental illness, particularly moderate conditions, but the system of diagnosis is still 200 to 300 years behind other branches of medicine,” said Dr. E. Jane Costello, a professor of psychiatry and behavioral sciences at Duke University. “On an individual level, for many parents and families, the experience can be a disaster; we must say that.”

-- “What’s Wrong with This Child,” New York Times, 11/11/06

Perhaps, at least in some cases, an avoidable disaster. A couple of years ago, I wrote a story for New Scientist magazine looking at links between a variety of infectious diseases and mental illnesses. Breakthroughs in molecular diagnostics and new technologies for peering inside the intact skulls of living patients had unmasked a number of pathogens --  viruses, bacteria and parasites -- capable of causing neurological destruction and behavioral chaos.

Ron Kessler, a professor of Health Care Policy at Harvard Medical School, and the lead researcher on several projects looking at mental health statistics both in the U.S., and internationally for the World Health Organization, is acutely aware of the conundrum: “I think that all functional psychiatric disorders are residual categories in the sense that they’re essentially saying, ‘This is an illness we can’t find anything physical for it yet.’ It doesn’t mean that it doesn’t exist. It means right now as far as we know we can’t find one.” 

Kessler also points out that while schizophrenics tend to have fewer (if any) children than non-schizophrenics, the rate of the disease has remained constant: about 1% of the population. If schizophrenia were strictly a genetic illness, one would expect the rate to whittle down eventually to nothing. (The symptoms of schizophrenia are so debilitating, most sufferers intersect with the mental health system, so the data on schizophrenia are unusually solid for a mental illness.)

The evidence for other causes, including infectious disease, has been growing. Evolutionary biologist Paul Ewald, who has written extensively on the evolution of infectious disease, has raised serious questions about the twin studies used to support the case for a genetics. Although identical twins who share 100% of their genes in common are more likely to both develop schizophrenia if one twin has it (concordance) than are fraternal twins or full siblings sharing only half of their genes, the concordance rate is considerably lower than a straight genetic-cause model would suggest. If schizophrenia were strictly genetic, concordance should be 100%. And since identical twins share all their genes, this should true no matter how many genes are involved. But the concordance rate is just 50%

Ewald then changes focus to consider the womb environment. A fetus develops wrapped inside two porous sacs, the inner chorion and the outer amnion. Nearly 70 per cent of identical twins share a chorion, a feature that can be determined after birth by the presence of subtle physical traits such as mirror-image fingerprints. Those twin pairs are nearly six times as likely to be concordant for schizophrenia as identical twins with separate chorions.

Meanwhile, the concordance rate for non-identical twins is nearly twice that of full siblings, even though the genetic relationship is the same: 50%. Fraternal twins rarely share sacs, but they do share a womb. That, says Ewald, points to an environmental factor; though not necessarily to an infection.

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There isn’t enough funding, lab space or time in the world, using traditional methods, to test for diseases that can take months, years, or even decades to cause clinical symptoms. And if symptoms are caused by auto-immune response, there may no organism to culture.

Fortunately, new techniques based on the genetic signatures of pathogens, as well as the immune responses they trigger, have given scientists better, faster diagnostic tools.

But hunting for microbial fingerprints is only part of the story. Combing through old medical records can reveal historical patterns of infection. Psychiatrist E. Fuller Torrey, associate director of research at Maryland-based Stanley Medical Research Institute, and his colleague Judy Miller, have sifted through two centuries-worth of asylum records from England, Ireland, Canada and the U.S. looking for evidence of an “invisible plague” of mind-addling diseases.

First, they had to account for changes in terminology (e.g., schizophrenia and bipolar disorder were formerly lumped together as “insanity,” while depression was “melancholia”). Next, annual case totals were converted into rates per 1,000 population to make it easier to compare data.  Since mortality rates were generally higher in institutions, the accumulation of older cases didn’t significantly skew the data: Deaths more than made up the difference. Also, note Torrey and Miller, asylums were simply too expensive to build unless there was an obvious need.

Statistics for Canada’s Atlantic costs provinces and the U.S. also show an upward trend throughout the 19th and early 20th centuries. The Irish stats, however, trump them all, spiking almost 32-fold between 1817 and 1900 (0.15 to 4.74 per 1,000). By 1961 the rate reached 7.13 per 1,000.

Perhaps most intriguing of all, Torrey and Miller have charted shifts in the regions where mental illness rates were particularly high, suggesting local outbreaks. 

It is impossible to say with any certainty what exactly lies behind those numbers, but infectious disease offers one potential explanation. Trade and travel increased dramatically during this period, providing new routes for exotic pathogens to spread, and hosts to infect. Some, a la syphilis, may have caused psychiatric symptoms.

Land development also could have brought people into closer contact with new germs. Even something such as the Irish famine of the mid-1880s could have set the stage for an outbreak of mental illness. Studies of a famine in the Netherlands during WWII -- the result of a Nazi blockade -- have linked a lack of micronutrients such as folate during pregnancy with an increase in neural tube defects and schizophrenia in offspring. Starvation also increases vulnerability to pathogens. Maternal exposure to a number of diseases -- including influenza  --  has also been linked to schizophrenic disorders in their children

The past may provide clues, but no definitive answers. So researchers at Columbia University in New York have teamed up with the Norwegian Institute for Public Health for the largest prospective neurodevelopmental study ever.  Dubbed the “Phenome Project” and “Baby Framingham” (after the famous long-range study on heart disease), scientists have begun charting the health of 100,000 children, beginning in the first trimester of pregnancy, along with the health of their mothers and fathers.  Although the initial focus of this long-range study is autism, the goal is to identify the origins of various neuropsychiatric and chronic conditions.

“Everybody says this is impossibly complex, but it’s not. What it requires is molecular epidemiology, genetic epidemiology, and the ability to take all these data and process them so you can understand associations,” says Columbia epidemiologist Ian Lipkin. “I am very optimistic that this is going to reveal all sorts of links.”

Even invisible plagues can be seen given a large enough data bank. And an enemy that loses its camouflage is that much easier to fight.