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
accept.
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
birth.
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
sclerosis.