BY: Jamie Talan, Staff Reporter

A team of investigators has identified infectious agents in the

blood of women pregnant in the 1950s and 1960s that may unlock some of the great mysteries

about the origin of mental illness.

The children of mothers who showed evidence of an infection –

either feline toxoplasmosis or herpes simplex virus type 2 – during pregnancy were four to

seven times more likely to develop schizophrenia than those children whose mothers had no

sign of infection during pregnancy.

The findings, reported jointly by scientists at Harvard School of

Public Health and Johns Hopkins Medical Institutes, offer strong support that a virus or

other infectious agent may alter the the developing brain and set in motion a process that

only decades later will reveal itself as schizophrenia.

The data were presented for the first time last month at the

International Congress on Schizophrenia Research, in Santa Fe, NM.

One in 100 people suffers from schizophrenia, a puzzling disorder

that can cause hallucinations, delusions and more pervasive problems in a person’s ability

to think clearly and behave normally.

Doctors say symptoms often first appear in young adulthood – at

the same period when the brain stops developing.  No one knows what triggers the

first symptoms of schizophrenia. Scientists expect that it may be a developmental problem

that kicks in once the brain reaches maturity. Others suspect that the stress of young

adulthood can trip the brain switch that produces symptoms at this time in life.

Examining the brain itself has provided few hints: many have

enlarged ventricles and slightly smaller frontal lobes (the area of the cortex that

processes human thought) but the core defect has yet to be identified.  Tissue

studied at autopsy is equally unrevealing; There is no pathological dame.

The handful of genes linked to families with high incidence of

schizophrenia have not withstood scientific scrutiny, and the hunt continues.

Viral theories have been put forth as well, but dismissed because

of the disease’s perfect epidemiological profile: Anywhere in the world, one out of 100

people suffers from schizophrenia.  Or at least that’s what scientists have come to


The latest bunch of viral hunters – Harvard’s Stephen Buka and

Hopkins Dr. Robert Yolken – happened onto a fabulous collection of records, including

blood samples from mother and child, that had been stored in federal files for more than

25 years.  This treasure trove of blood and health files has unearthed findings that

could send the field in new directions for both prevention and treatment.

Hidden in these files, one of the largest studies undertaken in

the 1950s to figure out the causes of cerebral palsy, the scientists would find what may

be the earliest antecedents of schizophrenia.  Two infectious agents – herpes simplex

virus type 2 and toxoplasmosis – may somehow transform the perinatal environment and alter

the brain, researchers speculate.

Buka was inspired by Dr. E. Fuller Torrey, a schizophrenia expert

who now runs the Stanley Foundation Research Programs in Bethesda, MD. Torrey has always

been interested in viral causes, and now that he was in charge of handing out research

money, he urged Buka, a research-generation younger, to find the health histories of those

who participated in the cerebral palsy study.

And after two years of working through the federal system, the

information from the National Collaborative Perinatal Project – hundreds of thousands of

files and test results from 55,000 mothers and their children – would come alive again.

This time, it was the search for clues to mental illness.

One of the biggest groups in the perinatal study was right in

Buka’s backyard, Boston and Providence, R.I. In these cities, the studies followed 16,000

women through pregnancy and their children until age 7.

Buka set out to find them again, searching for the one in 100 with

schizophrenia.  Buka found 2,500 of the families from the Providence area and 25

were, in fact, now schizophrenic, he reported at the Santa Fe meeting.  Three others

suffered from bipolar disorder, or manic-depression.

Then, Buka identified 56 children with no psychiatric illnesses

and matched them to the schizophrenic patients in age, sex, race and month and year of


The beauty of the perinatal study was that blood had been taken

from the mothers several  times throughout pregnancy, and cord blood was taken from

the children at birth.  These samples had been stored at minus 70 degrees C for all

these years.

Buka had asked Robert Yolken, a respected

pediatrician-turned-virologist at Hopkins, to analyze the blood samples and test for all

sorts of infectious agents.  Yolken ran several types of assays to test for

antibodies and other immune markers.  Raised against infection by the body’s immune

system, antibodies linger for months as a sign that an infection had recently done battle.

He also looked for immune markers called cytokines for evidence of fetal distress.

By the time Yolken finished his analysis, he had tested three

samples from each woman and one from their children.  It was now January and the

deadline for the schizophrenia meeting was fast approaching.

Yolken and Torrey flew up to Boston to analyze the findings.

Before Buka turned on his computer to reveal his information, the three hashed out the

hypothesis, once again, of what they hoped to find.

In 1995 Torrey and Yolken had co-written a paper in Schizophrenia

Bulletin titled: “Could Schizophrenia Be A Viral Zoonosis Transmitted From House

Cats”.  In the study, they polled a random sample of 165 parents of

schizophrenia patients who were members of the National Alliance for the Mentally Ill and

an equal number of community members without mentally ill children.  They found that

51 percent of the schizophrenic patients had been exposed to a house cat during childhood

compared to 38% of controls. A second, larger study of 726 subjects had confirmed these

early results.

So when Buka’s computer buzzed with historical data, it was no big

surprise that the schizophrenic children were 4.5 times more likely to have mothers whose

blood showed antibodies to toxoplasmosis – the infectious feline agent transmitted from

cat feces – compared to the control children.

But the real surprise was that the blood from these mothers whose

children wer now sick with a devastating brain disease were 7.5 times more likely to have

antibodies against herpes simplex type 2.

It is still unclear what these findings mean in terms of diagnosis

and prevention. Not all children exposed to these infectious agents during fetal

development go on to develop schizophrenia. In fact, while 57 percent – 16 of the 28

schizophrenia patients – had been exposed to toxoplasmosis or herpes type 2, so too had 20

percent, or 11 or 55 of the mentally healthy controls.

None of the other infectious bugs studied – influenzae, rubella,

cytomegalovirus or chlamydia – were found to affect the outcome of schizophrenia in this

sample, Buka reported at the meeting.

The researchers speculate that a stressful pregnancy could provoke

activation of the herpes simplex virus and and perhaps lower immunity against feline

infections.  It has long been recommended that pregnant women avoid cleaning cat

litter boxes because of the harm from toxoplasmosis.  Children exposed during

development can suffer a range of problems including low I.Q. and coordination problems.

Now, it seems, there may be far more subtle problems undetected for decades.

This latest finding supports work reported earlier this year from

a large epidemiological study in Denmark. Researchers found strong evidence that people

are at increased risk of schizophrenia if they lived in packed cities or were born in the

winter months – again a suggesting that infections are involved.

What do the findings mean? “It means that we got a lot more

work to do,” says Torrey. “Nobody should change their habits or get rid of their

cats, for now” he said.  “It has certainly produced promising leads to

consider as we try to understand schizophrenia.”

Unknown Virus Is Trigger Suspect

An unidentified retrovirus has been found in the cerebrospinal

fluid of people experiencing their first symptoms of schizophrenia, a finding that raises

troubling questions about the triggers of this serious mental condition.

Dr. Robert Yolken of Johns Hopkins Medical Institutions took

spinal fluid samples from 35 first-episode patients, 17 others who relapsed, 20 chronic

patients and 18 unaffected controls.  He reported last month at the schizophrenia

meeting in New Mexico that he found high levels of a retrovirus in the patients who had a

recent onset of their disease.

Yolken found that 29 percent of the first-episode patients had

evidence of a retrovirus compared to 12 percent of those who experienced a relapse.  

By comparison, 5 percent of the chronic patients had retrovirus circulating in their

spinal fluid compared to none of the control patients.  So far, they have ruled out

known retroviruses such as AIDS, he said.

Yolken has identified similar viruses from the blood. He suspects

that these are dormant viruses that may become active and somehow work on the brain to

trigger symptoms. Interestingly, he and his colleagues have found that the treatment with

antipsychotics actually bring about a drop in viral levels in the blood and spinal fluid.

Yolken collaborated with German researcher Silke Bachmann. The

spinal taps had been done to rule out encephalitis.

Similar findings have been observed in some patients with multiple