-Caveat Lector-
Steve,
As a person raised around cats most of my life I have made an
observation. Cats themselves have what a vet friend used to call the "cat
crazies". This is when for instance a quiet dozing cat will suddenly jump up
like a bat out of hell, tear around the room chasing heaven knows what, meow
and vocalize at no one or nothing in particular, run up the drapes, etc.
This behavior is most commonly observed in young cats but will occasionally
be seen in all cats.
Some people who I have known the smoke reefer have been known to
blow a little smoke at their cat. The report that they instantly get the cat
crazies. Cat themselves seem to have an interesting brain / thought process
pattern so its not entirely impossible that some of this might "rub off" on
the humans in their lives. Whether this is due to a virus or not I can't say
(as no one has ever stood up to vouch for my sanity ever).
I enjoy cat behavior very much but many people absolutely detest
cats. Do you know that the only member of the cat family mentioned in the
bible is the lion (in the old or new testaments). This is very strange
because the Egyptians just about worshiped cats and thought very highly of
them.
Also cats will often find you and just walk into your life ( and
sometimes leave that way too).
magnetic_field
^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
----- Original Message -----
From: "Steve Wingate" <[EMAIL PROTECTED]>
To: <[EMAIL PROTECTED]>
Sent: Friday, March 22, 2002 5:10 AM
Subject: [CTRL] Do Cats Cause Schizophrenia?
> -Caveat Lector-
>
> Pet Theory
> Do Cats Cause Schizophrenia?
>
> by Stephen Mihm
>
> http://www.linguafranca.com/print/0012/cover_pet.html
>
> "I THINK CATS ARE GREAT," says E. Fuller Torrey. His office decor would
seem to
> confirm this statement: A cat poster hangs on one wall; a cat calendar
sits on
> his desk; and a framed picture of a friend's cat leans against the
windowsill.
> He even admits to having a "cat library" at home.
>
>
> But Torrey's interest in felines is a bit different from that of your
typical
> cat lover. That's because Torrey, a psychiatry professor at the Uniformed
> Services University of Health Science and the enfant terrible of mental
health
> research, believes that Felis domestica may carry infectious diseases that
> could cause schizophrenia and bipolar disorder. "My wife thinks I'm going
to be
> assassinated by cat owners," says Torrey with a sigh. "In fact, I like
cats.
> Unfortunately, if we are correct that they transmit infections..." Here
his
> voice trails off, and he pensively fingers his closely cropped beard.
>
>
> Torrey often speaks in a self-deprecating manner of his "delusional"
notions,
> but he's dead serious about the cat connection. He thinks "typhoid
tabbies" are
> passing along Toxoplasma gondii, a parasite that causes brain lesions and,
if
> Torrey is right, schizophrenia.
>
>
>
> Torrey first made the argument nearly thirty years ago. "It was considered
> psychotic," he admits. But since then, his ideas, though still outside the
> mainstream, have attracted converts, most notably the Johns Hopkins
virologist
> Robert Yolken, with whom he now collaborates. Together, they're trying to
prove
> that toxoplasmosis is but one of several infectious diseases that cause
most
> cases of schizophrenia and bipolar disorder. It helps their case that
previous
> explanations-bad mothering, bad genes-have proven deficient to varying
degrees.
> But Torrey and Yolken have also uncovered some hard evidence to support
their
> claims, and they are about to put their theory to the test with clinical
trials
> of drugs that are new to the psychopharmacological arsenal: antibiotics
and
> antivirals similar to those used by AIDS patients. If the duo finds that
such
> drugs alter the course of schizophrenia, Yolken observes, their results
"would
> represent a major advance in the treatment of this devastating disease as
well
> as in understanding its basic etiology."
>
>
> "SCHIZOPHRENIA is a cruel disease," Torrey has written, with considerable
> understatement. Although it affects only 1 percent of the population,
> schizophrenia is among the most debilitating forms of mental illness.
Trapped
> in a world of private delusions, a schizophrenic might cling, for example,
to
> the belief that he is Jesus Christ, or that the government has implanted a
> monitoring device in his mouth during a routine dental procedure. Visual
and
> auditory hallucinations can range from the terrifying to the merely
strange:
> gigantic spiders, voices that insult or instruct. Some schizophrenics
withdraw,
> becoming mute or catatonic; others remain communicative but incoherent,
jumping
> from one topic to another without logical connections.
>
>
> With little or no warning, schizophrenia usually manifests itself in
patients
> between the ages of sixteen and thirty. From then on, the illness waxes
and
> wanes, with symptoms generally becoming less severe as the patient ages.
> Psychotherapy is of little help to schizophrenics, but medication and
constant
> medical care enable over 50 percent to make a full recovery. Still,
relapses
> are common, and many patients spend their lives in halfway houses and
> institutions. Approximately 40 percent of schizophrenics don't get the
help
> they need and end up on the streets or in prisons-or committing suicide.
>
>
> There has never been a consensus on schizophrenia's etiology or cause.
Many
> nineteenth-century psychiatrists thought it was a biological disorder;
some
> speculated that it might have an infectious origin. As far back as 1845,
the
> French neurologist Jean E. Esquirol wrote that "mental alienation is
epidemic."
> He added: "It is certain that there are years when...insanity seems
suddenly to
> extend to a great number of individuals." In 1874, the American Journal of
> Insanity published a lengthy brief titled "On the Germ-Theory of Disease."
By
> the early twentieth century, doctors like Eugen Bleuler had suggested that
"the
> connection of [schizophrenia] to infectious process equally needs further
> study." An outbreak of psychoses after the 1918 influenza epidemic and the
> discovery that syphilis could cause dementia lent further credence to such
> theories. In 1922, the psychiatrist Karl Menninger hypothesized that
> schizophrenia was "in most instances" the by-product of viral
encephalitis.
>
>
> Menninger later became a prominent Freudian psychoanalyst, following a
career
> trajectory that mirrored a larger movement in American psychiatry away
from
> biological explanations of mental illness. By the 1950s, Freudian thought
had
> solidified its grip on the American psychiatric profession. That also
happened
> to be the time when Torrey first began thinking of a career in psychiatry.
>
>
> As he tells it, the formative event for him came between his second and
third
> years at Princeton. His sister, who was due to start college that fall,
began
> hallucinating and yelling, "The British are coming!" The diagnosis was
acute
> schizophrenia. "My mother was told that it was because my father had
died,"
> Torrey says with disgust. "I thought, 'This is absurd-a lot of people's
fathers
> die and they don't develop schizophrenia.' There was this disconnect
between
> what I was looking at and what I was being told."
>
>
> As Torrey wrapped up his degree at Princeton and went on to medical school
at
> McGill, he began seriously to contemplate a career in psychiatry. After
two
> years as a Peace Corps doctor in Ethiopia and a year in the South Bronx
helping
> to set up one of the area's first neighborhood health centers, Torrey
began a
> psychiatry residency in Stamford, Connecticut. "It looked to me as if
> psychiatry was at least twenty years behind the rest of medicine," he
recalls.
> "It was more likely to move and be exciting during my practicing
lifetime."
>
>
> That wasn't what attracted most people to the field in the 1960s. Says
Torrey,
> "Psychiatry was the thing you could do if you found yourself in medical
school
> and realized that you had made a terrible mistake-that giving people
rectal
> exams was pretty unsavory and not what you wanted to do. You could still
be
> paid to be a doctor and talk to people about their problems." Those
problems
> didn't include schizophrenia, Torrey remembers: "To specialize in
schizophrenia
> was about the lowest form of psychiatric practice."
>
>
> Torrey was undeterred. Not long after he went to work as a special
assistant to
> the director of the National Institute of Mental Health (NIMH), he
attracted
> controversy by publishing a bruising attack on Freudian psychoanalysis. In
The
> Death of Psychiatry (Chilton, 1974), Torrey argued that psychiatry should
> either limit itself to the treatment of patients with severe brain
> disorders-schizophrenia, bipolar disorders-or abandon its medical
pretensions
> altogether. In 1976, he moved from NIMH to St. Elizabeth's Hospital in
> Washington, D.C., where he achieved considerable renown as an advocate for
the
> seriously mentally ill. He also helped found the National Alliance for the
> Mentally Ill, a nationwide patient advocacy group.
>
>
> The turning point in Torrey's career came in 1983, when he published two
books:
> Surviving Schizophrenia, which soon became the authoritative text for
patients
> and families; and The Roots of Treason, a biography of Ezra Pound based on
> research conducted at St. Elizabeth's. The second book, which was
nominated for
> an award by the National Book Critics Circle, was inspired by rumors that
Pound
> had sought refuge at St. Elizabeth's after World War II to avoid standing
trial
> for treason. When Torrey researched the case, he discovered that a
hospital
> administrator had colluded to protect Pound by declaring him insane. It
was a
> great piece of detective work, but the book earned Torrey a demotion at
St.
> Elizabeth's. Disillusioned, he retired two years later and began pursuing
his
> unorthodox theories of schizophrenia. That meant getting inside the brain
of
> the schizophrenic-literally.
>
>
> "THE BRAIN is in a very inconvenient place," says Torrey, guiding me up
the
> walkway to a boxy white building on the grounds of the Naval Hospital in
> Bethesda, Maryland. "People just don't like you opening up their heads and
> looking around while they're alive." This building, he tells me, houses a
> solution to that problem. He opens a door and we enter what looks and
smells
> like the maintenance area of an indoor pool. "The Navy has a dive chamber
> here," says Torrey, pointing to something that looks like a beached
bathysphere
> in the middle of a large warehouse. "We're sharing space with them for
now."
>
>
> This is home to the Stanley Foundation Brain Bank and Neuropathology
> Consortium's laboratories. Scattered throughout the building's corridors
and
> storerooms are some fifty-five freezers containing the brains of about 385
> people-schizophrenics, manic depressives, people with severe depression,
and so-
> called normal controls. The bank obtains the brains with the assistance of
> designated medical examiners and the permission of surviving family
members.
> Each brain comes with a complete set of medical records, family medical
> histories, and other clinical information. The brains are then made
available
> to mental illness researchers worldwide, including Torrey and his
colleagues.
> The whole undertaking, along with a number of related projects, is funded
by
> Theodore and Vada Stanley, wealthy philanthropists who made their money
selling
> mail-order collectibles. (In one of his many roles, Torrey is the
executive
> director of the Stanley Foundation, an organization that dispensed some
twenty-
> one million dollars in research funds last year.)
>
>
> As we wind our way down hallways packed with gigantic freezers, Torrey
stops to
> turn on the light in what looks like a storage closet. "Here are the
brains,"
> he says, pointing to countless plastic pails stacked on metal shelves. "We
put
> half of each brain in formalin and half in the freezers." Torrey turns out
the
> lights. "Sometimes I take a brain to show my students. They always enjoy
that."
>
>
>
> We enter the room where most of his staff work. Torrey is in his element,
> clapping pathologists on the shoulder, joking with them, seemingly
oblivious
> (unlike me) to the business at hand: carving up brains with what looks
> disturbingly like the meat slicer used at the local deli. The staff are
equally
> upbeat, even when describing the downside of the work. "It can be a little
> depressing at times," admits Dr. Maree Webster, who runs the bank. "Many
of the
> brains are from suicides, that sort of thing. It's really tragic."
>
>
> The Brain Bank is the culmination of Torrey's dream to study schizophrenia
from
> the inside out. He hopes that the collection will ultimately lead
researchers
> to the cause of the disease. As for himself, he's hoping that one day he
and
> his colleagues will find their hypothetical virus, though, as Webster
admits,
> "it's a little like trying to find a needle in a haystack. The brain is a
big
> place."
>
>
> And viruses are pretty small.
>
>
> TORREY DATES his obsession with infectious disease to the early 1970s. "I
was
> becoming aware of proven cases of viral encephalitis that had been
diagnosed as
> cases of schizophrenia or cases of manic depressive illness," he recalls.
> Torrey discovered some of the cases in the work of Menninger and others
near
> the turn of the century. It was also during the 1970s that the future
Nobel
> Prize winner Daniel Carleton Gajdusek published some of his first research
on
> so-called slow viruses-pathogens that lie quiescent for twenty or thirty
years
> before emerging as full-blown infections.
>
>
> Intrigued, Torrey met with Gajdusek. In conversation, the elder scientist
> mentioned a trip he had made to the highlands of Papua New Guinea to
catalog
> neurological disorders. He told Torrey that he had never found a
cut-and-dried
> case of schizophrenia there, despite the fact that the disease is supposed
to
> afflict about 1 percent of the world's population. Torrey himself made
several
> trips and confirmed as much. "But on the coast," he recounts, "where there
had
> been missions and contact with outsiders for a hundred years, you found
> occasional cases." To Torrey, that raised the tantalizing possibility that
some
> kind of infectious agent was at work.
>
>
> Torrey's theory started to look even more plausible when he began to
> collaborate with Robert Yolken, who now runs the Stanley Division of
> Developmental Neurovirology, based at the Johns Hopkins Children's Center.
> Yolken, a summa cum laude graduate of Harvard who stayed on for a medical
> degree, is a study in contrasts with Torrey. Whereas Torrey spins stories
and
> lingers on words for effect, Yolken speaks without affect at an
extraordinarily
> rapid rate, as though his tongue can barely keep pace with his brain.
Pictures
> of ski vacations with his family and Torrey are taped to the shelves above
his
> computer.
>
>
> When the two scientists began working together in the 1980s, genetic
> explanations had usurped traditional psychoanalytic theories about the
cause of
> schizophrenia. The new biological paradigm held that it was only a matter
of
> time before some hypothetical "schizophrenia gene" would be identified,
solving
> the mystery. But Torrey and Yolken remained skeptical. There were some
things
> that genetics couldn't explain. For starters, several studies had shown
that
> children born in urban areas were more likely to develop schizophrenia
than
> those born in rural regions. Household crowding, too, had been
demonstrated to
> be a risk factor. And both urban living and household crowding increase
> exposure to infectious agents.
>
>
> Schizophrenia also appeared to correlate with birthdays. More than 250
> epidemiological studies, including some of Torrey's own, have demonstrated
that
> both schizophrenic and manic depressive patients are between 5 and 15
percent
> more likely to have been born in the winter or spring months. Part of that
> statistical bump, in Torrey's opinion, could be attributed to the
increased
> rate of viral infection in the colder months. "The seasonality data make
the
> geneticists very uncomfortable," says Torrey.
>
>
> Paul Ewald, a professor of biology at Amherst College and a specialist in
> infectious diseases, is a bit more blunt. "With schizophrenia, you have
> seasonal correlations, which is a telltale sign of infectious agents.
There are
> not that many things that can explain that association," he says. "Unless
you
> believe in astrology."
>
>
> Ewald is little known in mental health circles, but his theories have
already
> earned him considerable attention among infectious disease specialists. He
and
> his collaborator, Gregory Cochran, believe that many diseases-heart
disease,
> various forms of cancer, multiple sclerosis, cerebral palsy, most major
> psychiatric diseases-are often caused by infectious agents. Their
reasoning is
> simple: Any gene that adversely affects an individual's ability to
reproduce
> and care for offspring will ultimately fall victim to natural selection.
> Therefore, severe common diseases-those having an incidence higher than
one in
> a thousand-can't be chalked up simply to bad genes. Some kind of
environmental
> factor, either infectious or noninfectious, must play a role as well.
>
>
> Schizophrenia, says Ewald, must be one of these diseases, because it
seriously
> diminishes a person's reproductive fitness. At the same time, neither he
nor
> Torrey and Yolken suggest that genetic factors are irrelevant. After all,
> there's plenty of evidence that genes play a role in schizophrenia. One
measure
> of that is the monozygotic twin test, which yields the percentage of
identical
> twins who both develop a particular disease. A concordance rate of 100
percent
> is evidence of a purely genetic disease, one that is little influenced by
> environmental factors like infection, nutrition, or toxins. Huntington's
> disease, for example, has a concordance rate of 100 percent. Similarly,
Down's
> syndrome has a concordance rate of 95 percent; autism, 82 percent. By
contrast,
> a viral infection like polio has a concordance rate of only 36 percent
among
> identical twins-thus, genetics plays some role, but most of the blame lies
with
> the polio virus. What about schizophrenia? According to Torrey's
> (controversial) calculations, the concordance rate averages approximately
28
> percent. With a rate that low, says Ewald, "we have to look elsewhere."
>
>
> For Torrey, Ewald, and others, that means looking for some kind of
infectious
> agent that may exploit a genetic weakness when invading a host. This
interplay
> of genetics and infectious disease is complex and has a lot to do with
whether
> a faulty gene permits the virus, bacterium, or parasite in question to
lock
> onto cells. As Yolken explains it, these "genetic determinants" are
different
> from those involved in typical "genetic" diseases like Huntington's in
that a
> person's genetic susceptibility doesn't surface unless he or she comes
into
> contact with a particular environmental factor. In theory, that's why one
> identical twin and not the other will come down with schizophrenia: Only
one is
> exposed to the "schizovirus."
>
>
> Torrey says that these theories aren't news to most people in the medical
> profession, particularly those working with infectious diseases.
> "Psychiatrists," he notes in an exasperated tone, "are the only ones that
are
> surprised by this."
>
>
> TORRY IS talking about cats again. "I've given talks on the cat stuff and
> people's response is almost universal: 'I'm not surprised-I've known my
cat is
> schizophrenic for years!'" He chuckles. "One talk I gave at a department
of
> psychiatry, a fellow came up to me and said, 'I don't want you to repeat
this,
> but the former chairman of our department of psychiatry was convinced that
his
> cat was hallucinating, so he gave him liquid Thorazine and it really
seemed to
> help.'" Torrey looks at me and smiles. "People find cats strange, so they
don't
> find this idea so odd."
>
>
> Yolken, who owns two cats, is less critical of our feline friends, but he
> agrees that there may be a connection. "Cat feces are the biggest source
of
> toxoplasma infections in the United States," he says, preparing to guide
me
> through a PowerPoint presentation at his desk. Toxoplasma, Yolken informs
me,
> is one of the more adaptable parasites, able to set up shop in any number
of
> mammals. Although most humans can battle, or even carry, toxoplasma
without ill
> effects, the parasite poses a special danger to people with compromised
immune
> systems. It is also hazardous to pregnant mothers and their fetuses,
causing
> serious brain lesions and retardation in infants when contracted during
the
> first trimester of pregnancy. That's why doctors now forbid expectant
mothers
> to clean litter boxes. Torrey and Yolken speculate that a toxoplasma
infection
> contracted during pregnancy or infancy could lie dormant in some patients'
> central nervous system, only to be reactivated when the host's immune
system is
> compromised by a secondary infection in late adolescence.
>
>
> Cats, meanwhile, don't seem to suffer toxoplasma's ill effects. They pick
up
> the parasite from eating infected rodents, typically rats or mice. In the
> rodents themselves, the parasite produces brain lesions and a host of
rather
> odd behaviors. Infected rats, for example, lose their instinctive fear of
cat
> urine, making them more likely to be caught and eaten by feline predators.
As
> Ewald explains, "The parasite gets to the next host in its life cycle by
> messing up the rodents' minds." Once in the cat, the parasites infect the
> lining of the small intestine, reproduce asexually, and encase themselves
in a
> sturdy membrane. These oocysts, or spores, are then shed in the cat's
feces.
> The cycle begins anew when human beings and other mammals become infected
from
> handling the feces or, in some cases, breathing and swallowing the
airborne
> spores.
>
>
> Torrey first postulated that toxoplasmosis might cause schizophrenia in
the
> 1970s, when he read several articles attributing an outbreak of multiple
> sclerosis in the Faeroe Islands to the introduction of dogs there during
World
> War II. Could indoor pets like cats, which had become widely popular only
in
> the nineteenth century, also be reservoirs of infectious agents? Torrey,
who
> had recently completed a book manuscript arguing that in the late
nineteenth
> century schizophrenia and bipolar disorder went from being rare diseases
to
> relatively common ones, became convinced that cats were central to that
story.
> "The cat craze began with the cat shows in the late nineteenth century,"
he
> explains. "And when I went back and looked at what we know about cats as
pets,
> it corresponded almost perfectly to what we know about the rise of
psychosis."
>
>
>
> Eager to test the theory, he and Yolken conducted a study in the early
1990s
> wherein parents of schizophrenics and nonschizophrenics were asked whether
they
> owned a cat during pregnancy or when their offspring were young. That
study
> revealed a higher incidence of cat ownership among the parents of children
who
> developed schizophrenia (51 percent) versus those who did not (38
percent). A
> second study, much larger in scope, looked into nineteen different
factors,
> including cat ownership, dog ownership, complications during pregnancy,
breast
> feeding, and urban versus rural residence. Only five of the variables
proved
> statistically significant, cat ownership among them (52 percent of those
who
> developed schizophrenia had lived with cats versus 42 percent of the
> nonschizophrenics). Dog ownership, by contrast, was marginally more common
> among nonschizophrenics (78 percent) than among schizophrenics (73
percent).
>
>
> Such epidemiological data are further supported by a recent study by
Yolken and
> Stephen Buka of the Harvard School of Public Health. The two stumbled onto
> medical records and blood samples taken from some fifty-five thousand
pregnant
> women taken between 1959 and 1966 as part of a study on the causes of
cerebral
> palsy. Buka tracked down about twenty-five hundred families from
Providence,
> Rhode Island, who took part in the study. Among these families,
twenty-seven
> children had exhibited psychoses. Buka matched these with some fifty-four
> controls of the same age, sex, race, and month and year of birth. Yolken
then
> subjected the blood samples of both groups to a battery of tests for
different
> antibodies. The mothers of the children who later developed psychoses were
> approximately 4.5 times more likely to have antibodies to toxoplasmosis
than
> the mothers of the healthy controls.
>
>
> "It's been known for a long time that toxo can get into the brain," says
> Yolken. But can it cause schizophrenia? One bit of evidence, he says,
> comes from the AIDS epidemic. "It turns out," he explains, "that about 30
> percent of the adult population is toxo-positive"-that is, has antibodies
> to toxoplasmosis-"and that if you suppress our immune systems enough,
we'll get
> toxoplasmosis. Most HIV patients who are toxo-positive will
> eventually show signs of toxoplasmosis." Today many such patients get
> medication to prevent this, but a decade ago, Yolken recalls, "we saw
> massive toxo." He thinks it was probably there all along, hibernating in
the
> brain. So far, his and Torrey's attempts to find evidence of toxoplasma
> in the brains of schizophrenics have failed. "The brain is a big place,"
says
> Yolken with a sigh. "And it doesn't take much toxo to start an
> infection."
>
>
> Of the other diseases that Yolken tried to correlate with
> schizophrenia-rubella, influenza, cytomegalovirus, chlamydia, and herpes
> simplex 2
> (HSV-2)-only herpes was significant. Tests showed that mothers of
schizophrenic
> children were 5.8 times more likely to have antibodies to
> HSV-2 than mothers of the healthy controls.
>
>
> How might a herpes infection contracted in the womb lead to mental illness
> years later? As Yolken sees it, the age when most schizophrenics
> first develop symptoms suggests exposure to some sort of "infectious agent
> which has a higher rate of transmission in late adolescence and
> early adulthood." Yolken hypothesizes that the herpes virus remains
quiescent
> in the brain until adolescence, when it is triggered by the Epstein-
> Barr virus that causes mononucleosis, also known as the kissing disease.
> Another theory holds that it is reactivated by another version of itself
> picked up in sexual contact. How such an infection translates into
> schizophrenia is still a matter of considerable speculation. Yolken is
wary of
> saying that herpes causes schizophrenia. "These represent complex
disorders,"
> he says.
>
>
> Adding to the complexity, Yolken thinks that other kinds of viruses also
play a
> role in severe mental disorders. He and Torrey have just completed
> a study in which more than 17 percent of patients who recently manifested
> schizophrenia had antibodies to the multiple sclerosis retrovirus.
> Equally interesting to Yolken is evidence that in nearly 30 percent of
recent-
> onset schizophrenics, endogenous retroviruses had made copies of
> themselves. In both cases, the rate for the controls was zero percent.
>
>
> Endogenous retroviruses, admits Yolken, "are not well known in the
scientific
> community." They are viruses that are incorporated into the human
> genome. In other words, he explains, at some point in evolutionary
history,
> "progenitors of humans or primates got infected with a retrovirus, and
> the retrovirus got into the genome and stayed in the genome." As a
consequence,
> foreign bits of genetic material are scattered through the
> human genome. "In most cases, they don't seem to do very much," Yolken
says
> reassuringly. But it seems that in some cases they can be
> activated by other viruses. Then the little stowaways begin to make copies
of
> themselves, perhaps wreaking havoc on adjacent genes and,
> Yolken conjectures, triggering schizophrenia.
>
>
> If schizophrenia is caused by a virus, can it be cured? "What we don't
know is
> whether the infection is reversible," says Yolken. "If the damage is
> done in childhood, then treating patients as adults may not work." Still,
he
> and Torrey are going to try: They are administering acyclovir, an
> antiviral drug better known for its efficacy against herpes infections, to
> groups of schizophrenic patients. They're encouraged by several previous
> studies, including one of their own, which have shown that antipsychotic
drugs
> like Thorazine, Haldol, and clozapine inhibit viral replication.
> Torrey and Yolken hypothesize that the drugs' efficacy may have something
to do
> with their antiviral properties. In a subsequent trial, they will
> administer antibiotics customarily used to treat toxoplasmosis.
>
>
> ALTHOUGH Torrey and Yolken's theory that an infectious disease causes
> schizophrenia has gained some acceptance, or at least respect, it is
> still far from the prevailing view. Torrey in particular has many critics,
even
> among colleagues with whom he has collaborated.
>
>
> Take Irving Gottesman, a professor of psychology and clinical pediatrics
at the
> University of Virginia and a major proponent of genetic
> explanations of schizophrenia. The two men maintain a friendly
relationship
> despite their differences. "The thing that keeps us together," explains
> Gottesman, "is that we have common enemies: the Freudians, the
sociologists,
> the cultural anthropologists"-anyone, in other words, who wants
> to ascribe schizophrenia to nonbiological causes. They frequently
co-author
> articles attacking what they perceive to be misallocations of mental
> health research funds. But when it comes to explaining schizophrenia, they
part
> ways.
>
>
> Gottesman casts doubt on Torrey's data for the rate of concordance for
> schizophrenia among identical twins. "He's always trying to lower the
> rates," claims Gottesman. "I'm just doing it the way geneticists have
always
> done." Gottesman's statistical method, known among geneticists as
> probandwise concordance, samples admissions to a particular hospital. If
one
> member of an identical-twin pair shows up with schizophrenia
> and the other member shows up at a different hospital with schizophrenia,
too,
> then the twin pair counts as one concordant pair. But if one twin
> shows up at the hospital and the other twin shows up at the same hospital,
each
> twin counts as a concordant pair, thus yielding two pairs instead
> of one. This method produces a concordance rate that's close to 50
percent.
> "Geneticists use probandwise to avoid errors when comparing
> rates with the general population rate," explains Gottesman.
>
>
> "I call it a system of double counting," says Torrey of Gottesman's
method. "I
> don't know of any other people outside of psychiatry who use the
> probandwise concordance rate." Paul Ewald agrees. In an e-mail, he notes
that
> "proband concordance is vulnerable to overestimates on the
> basis of selection biases.... I trust Torrey's figures for schizophrenia,"
he
> writes. "They don't incorporate this bias."
>
>
> Nonetheless, Gottesman is certain that genes play a bigger role than
Torrey and
> his colleagues admit. In fact, Gottesman has helped formulate a
> multiple-gene theory of schizophrenia, which holds that the disorder
arises
> from a complex set of interactions between many different genes.
> He's also interested in what he calls epigenetics, the study of
environmental
> factors-drugs and other toxins, for example-that control or trigger
> gene events.
>
>
> "Viruses could be epigenetic contributors, too," concedes Gottesman. But
he
> will accompany Torrey only so far down that road. Back in 1994,
> when Gottesman and Torrey published the findings of a landmark study of
twins
> and schizophrenia, they offered their differing interpretations of
> the results not as a traditional conclusion but in the form of a fictional
> conversation among three experts. Gottesman, who spoke for the
> geneticists under the pseudonym Dr. Mendel M. Malgene, urged Torrey, who
> assumed the nom de plume Dr. Dena S. Daverus, not to dismiss or
> diminish the complex interplay of different genes. He also pointed out
that the
> brain scans they had conducted in the course of their study
> revealed broad, scattered types of changes in the structure of
schizophrenic
> brains. Infectious diseases like rabies or polio, by contrast, afflict
> very specific types of cells or regions of the brain. And anyhow, says
> Gottesman today, "If schizophrenia is caused by an infectious disease, why
> is it that psychiatric nurses and psychiatrists don't have higher rates?"
He
> pauses. "Why don't spouses of schizophrenics have higher rates of the
> disease?"
>
>
> JOINING Dr. Daverus and Dr. Malgene in the fictional schizophrenia debate
was
> Dr. A. Dominic D'Velupmoni, modeled after Daniel
> Weinberger, who in real life represents what has since become the dominant
> school of thought about the disease. Weinberger, who is chief of
> the Clinical Brain Disorders Branch Intramural Research Program at the
National
> Institute of Mental Health, is one of the most articulate
> spokesmen for what is known as the neurodevelopmental hypothesis. Writes
> Weinberger, "It has recently become de rigueur to refer to
> schizophrenia as a neurodevelopmental disorder in which the primary
cerebral
> insult or pathological process occurs during brain development
> long before the illness is clinically manifest." In other words, as
Weinberger
> explains it to me, something "disrupts the normal programs of brain
> development." That could be a faulty gene or an obstetric complication. Or
> something else: Like Gottesman, Weinberger is willing to consider
> that viruses might play a role. "Genetics can't explain it all," he says.
> "There have to be environmental factors, too, and viruses may be one of
> those." But though he describes Torrey's viral theory as "very
provocative,
> very interesting," Weinberger argues that "it's been supported by very
> little credible scientific data."
>
>
> The neurodevelopmental theory "is not a theory about a specific cause;
it's a
> theory about timing," counters Torrey. "We have fashions in
> schizophrenia research, and the neurodevelopmental theory is very
fashionable
> right now." As he sees it, Weinberger needs to explain what
> exactly causes the schizophrenic brain to develop in the way it does.
> Attributing some of that process to obstetric complications or
malnutrition
> during pregnancy, as some proponents of the neurodevelopmental hypothesis
do,
> doesn't add up. Areas of the world that have the worst prenatal
> care, diet, and rates of obstetric complications do not have higher rates
of
> schizophrenia; if anything, Torrey points out, the incidence of
> schizophrenia may be lower in such places.
>
>
> Neurodevelopmental thinking nonetheless remains at the center of current
> psychiatric accounts of schizophrenia. And though Torrey and Yolken's
> views currently sit on the margins, Ewald does not think they will remain
> there. "Infectious causation has been seriously underestimated from the
> 1800s onward," he notes. "Many people who suggested infectious causes of
> diseases were dismissed but later proven right." Take gastric
> ulcers. Only in the last decade did researchers prove that Helicobacter
pylori
> bacteria, not stress and hot food, cause most ulcers-even though
> evidence for this had been accumulating for over a century. With a disease
as
> complex and mysterious as schizophrenia, Ewald admonishes,
> researchers need to be careful not to reject infectious disease hypotheses
out
> of hand.
>
>
> To be sure, the field is less divided today than it was when Torrey began
his
> training some thirty years ago. Almost everyone in psychiatry now
> accepts the biological model of mental illness. No surprise, then, that
Torrey,
> Yolken, Gottesman, and Weinberger all admit that their theories may well
be
> compatible. At the same time, none shows much willingness to dilute a
life's
> worth of research with such compromise. "The best theory of all would be
one
> that integrates all of them without preconceptions," says Gottesman.
"But," he
> says sadly, "who's going to do that?"
>
>
> Stephen Mihm is the producer of The New York Times Magazine on the Web and
a
> doctoral candidate in history at New York University. He lives in New York
City
> with his three cats, all of whom declined to be interviewed for this
story.
>
> ------------------------
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