-Caveat Lector-

Get 100 volunteers. Randomly assign 3 to pet groups. Cat; small cat-sized
dog; rabbit; no-pet. Follow up with thorough psych testing. The cost would
be a pittance compared to the cost of treating cat schizos.
POC

On Fri, 22 Mar 2002, Steve Wingate wrote:

> -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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