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 Even
more convincing, in Andreasen's eye, are the five
or six MRI studies of newly diagnosed
schizophrenics conducted at centers in Australia,
Asia, Europe, and North America. These have shown
"substantial structural brain abnormalities,"
including overall smaller brain size, enlarged
ventricles, and other anomalies.
She
says one cannot conclude, based on these studies,
that schizophrenia damages any specific brain cells
or regions." A diligent search by many talented
neuroscientists has not identified any such
specific regional abnormalities or nerve cell
lesions," she writes. Instead, she theorizes that
schizophrenia is a "misconnection syndrome,"
meaning that it's a disorder that "damages the way
regions are connected to one another, so that a
breakdown in signal transfer occurs.… Like a
malfunctioning computer, the various nodes in brain
networks send information back and forth in a way
that causes file corruption, garbled information,
or crashes."
Andreasen
says PET scans (which measure changes in blood-flow
associated with brain function) have shown people
with schizophrenia to have abnormal blood-flow
patterns while performing a variety of tasks. "We
now suspect that the cerebellum may be
malfunctioning as a 'metronome' or timekeeper,
causing signaling to lose its synchrony and
coordination," she writes. "The thalamus, which
functions as a filter or gatekeeper that helps
determine how much information should be let in or
out of the brain, may be failing to screen
information out, so that the system becomes
overwhelmed with so much data that the person's
thinking becomes confused or
sluggish."
Brain
chemistry is yet one more area where Andreasen and
other psychiatrists see evidence of an organic
disorder in schizophrenics. Andreasen says
researchers early on noted that stimulants such as
amphetamines, which cause the brain to release lots
of the neurotransmitter dopamine, can produce
schizophrenia-type symptoms. Conversely, nearly all
antipsychotic drugs prevent dopamine molecules from
delivering chemical messages to the nerve cell
membranes that normally receive them. "These
observations led to the formulation of the
'dopamine hypothesis of schizophrenia' " in the
1960s, writes Andreasen. "Simply stated, it
suggested that the symptoms of schizophrenia were
due primarily to hyperactivity in the dopamine
system."
Although
this hypothesis "was universally accepted…for
nearly thirty years," Andreasen says that in the
past decade, "the plot has thickened" as
antischizophrenic drugs that block the function of
two other neurotransmitters, serotonin and
glutamate, have hit the market. The newer drugs,
known as "atypical neuroleptics," are believed to
work as well as and have fewer serious side effects
than the older generation of antipsychotics.
Andreasen writes, "Clinician scientists now think
that schizophrenia occurs as a consequence of a
much more complex chemical imbalance that includes
multiple neurotransmitter systems that interact
with and modulate one another."
Mosher
finds none of this convincing. "There are very good
critiques of the adoption studies and the twin
studies," he asserts. The problem with explaining
the higher concordance of schizophrenia among
identical twins by pointing to their shared genes
is that identical twins also share the same
environment to a greater extent than even
nonidentical twins. Mosher says a number of studies
have demonstrated that they're "clearly raised more
similarly than nonidentical twins or siblings.
People tend to dress [identical twins] more
alike. They look the same. They generate a similar
response. And they do have this sense of being one
person." So that shared environment may explain why
a higher percentage of both of them go crazy than
do nonidentical siblings.
One
traditional way of subtracting environment from the
picture in identical-twin studies has been to look
at pairs who've been raised separately. But, Mosher
says, so few identical twins are separated at birth
and later diagnosed with schizophrenia that there
aren't enough of them to be statistically
significant.
On
the other hand, you can find plenty of
schizophrenic parents whose offspring were raised
by adoptive parents, and a number of researchers
have examined what happens in such cases. Andreasen
cites two studies of adopted children who grew up
in families considered normal or healthy. Both
studies showed that the rate of schizophrenia among
children with a schizophrenic parent was the same
(about 10 percent) regardless of whether the
children were raised by the adoptive family or the
schizophrenic mother.
Mosher,
however, says both of these studies had major
methodological flaws. In contrast, he says a twin
study begun about 20 years ago by a Finn named
Tienari and an American named Wynne is "one of the
best pieces of research done this century." It
compared the outcome of children who had a
schizophrenic parent with that of children of
normal parents when both groups were placed in
normal adoptive families, and it found that the
children of schizophrenics developed schizophrenia
only slightly more often than the control group.
"So you can say, well, there's a little genetic bit
there, but it takes the family to make that bit be
expressed," Mosher says. One's genetic makeup "at
most may be a sort of background variable. But it's
so weak and so indefinable as to be useless in
terms of defining the condition."
As
for the abnormalities that researchers have found
with brain scans, Mosher thinks the
antischizophrenic medication accounts for much of
this. He says, "The Germans, who invented
neuropathology, looked at the brains of thousands
of schizophrenics before there were any
neuroleptics. And they were never able to find
anything. They never reported increased ventricular
volume, which at postmortem you can measure quite
easily. And they also never reported any specific
cellular pathology, and they studied many, many,
many brains." He adds that "there are a whole lot
of people who don't have schizophrenia and also
have enlarged ventricles. And there are people who
have other psychiatric conditions who have enlarged
ventricles, and there are a number of known causes
of enlarged ventricles that are not schizophrenia.
So, yes, there is a statistical difference, but it
is not specific."
"On
the other hand," Mosher continues, "there are
studies that have shown that people treated with
neuroleptics have changes in brain structure that
are at least associated with drug treatment,
dosage, and duration -- and have been shown to
increase over time as drugs are given." He cites
one "horrific study" of children between the ages
of 10 and 15 in which the researchers measured the
volumes of the kids' cortexes. "The cortex is what
you think with, the part on the outside," Mosher
explains. Over time, "They watched the cortical
volume of these young people decline, while the
cortical volume of the nonschizophrenic controls
was expanding because they were adolescents and
still growing." The researcher concluded that their
schizophrenia had caused the decrease in the
subjects. "And yet every single one was taking
neuroleptic drugs," Mosher says.
He
concedes that the German neuropathologists working
earlier in the last century didn't have access to
PET scans, a tool that Mosher categorizes as being
a significant advance. "They show you activity, not
just structure. They show which parts of the brain
are working at a given task. And okay -- there they
do find differences between people who've been
labeled schizophrenic and normal people." But how,
Mosher asks, can anyone tell if those differences
cause the psychotic behavior or result from it? He
says he's not at all surprised that the frontal
lobe metabolism of drug-naïve schizophrenics
looks different on PET scans than that of normal
people. "Because if you meet such people, you
know that they are in an unusual state of
consciousness. They may be going 100 miles a
minute. They may be totally distractible. You could
measure a lot of other things, and they'd all be
different at that point in time. But you don't know
if that's a cause or an effect of the way they
are."
Mosher
insists he could still be convinced that
schizophrenia is a disease. "If you show me
something -- either a lesion, meaning a structural
abnormality, or a particular neurophysiologic
process that is identifiable, can be replicated,
and is found only in those people who've been
labeled as having schizophrenia, and it's there
before the onset of the disorder -- I would change
my mind tomorrow. I've held that position for 30
years." But lacking that sort of evidence, he
argues that to label anyone as being schizophrenic
is to sentence them to a life of discrimination.
"It is a sticky label which, once given, is
extraordinarily difficult to get rid of," Mosher
says. If you have pneumonia and you get over it,
you're not forever more considered to be a person
with pneumonia. "You're fixed," he says. "But if
you are once labeled schizophrenic, the tendency is
you are always a person who will be called
schizophrenic. This is totally crazy. It violates
all the rules of
medicine."
It
also flies in the face of a number of studies that
have looked at how people fare many years after
being given a diagnosis of schizophrenia. Perhaps
the best-known American example of this research
was conducted by a psychologist named Courtenay
Harding. She decided to focus on a group of men and
women who had once inhabited the back wards of
Vermont State Hospital. "Middle-aged, poorly
educated, [and] lower-class," these people
had been hospitalized for an average of six years
and given long courses of phenothiazines when they
were chosen to be discharged and placed in a
community rehabilitation program in the mid- to
late 1950s. In the early 1980s, Harding and her
colleagues at Yale University managed to track down
what had happened to 97 percent of the 269 original
subjects. Using their medical records, the
researchers had independent experts rediagnose the
subjects according to updated criteria. In the
light of the more stringent modern standards, 118
subjects received a schizophrenia diagnosis, and 82
of them were still alive and willing to be
interviewed.
Contrary
to the researchers' expectations, the former mental
patients for the most part had encouraging stories
to tell. They had evolved "into various degrees of
productivity, social involvement, wellness, and
competent functioning," the resulting 1987 article
in the American Journal of Psychiatry
reported. Some 68 percent displayed no signs or
symptoms of their previous crazy behavior.
Furthermore, Harding's group wasn't the only one to
study long-term outcomes; at least four similar
efforts have been made. "Together these studies
found that one-half to two-thirds of more than 1300
subjects studied for longer than 20 years achieved
recovery or significant improvement," Harding noted
in another publication.
Nonetheless,
many doctors continue to believe that schizophrenia
"is a disease that's always there," Mosher
complains. People like John Nash -- the Nobel
Prize-winning mathematician whose recovery from
schizophrenia was dramatized in A Beautiful
Mind -- are "a thorn under [their]
saddle," he says. Mosher was appalled by the way
the movie seemed to credit the pharmacological
industry for Nash's return to sanity. This occurs
when a representative of the Nobel committee comes
to visit actor Russell Crowe at Princeton in the
early 1990s, and Crowe/Nash declares, "I take the
newer medications." Mosher points out that in fact
Nash has stated on numerous occasions that he has
not taken any antischizophrenic medication since
1970.
Harding's
study of the former mental patients in Vermont
offers confirmation that a drug-free recovery like
Nash's was no fluke. Half the subjects interviewed
in the 1980s never took any psychotropic
medication, and an additional 25 percent said they
took it only sporadically. All of those who had
fully recovered had long since stopped taking
medication, the American Psychiatric Association's
Monitor quoted Harding as stating in
February 2000.
There's
some debate over whether a massive study of
schizophrenic outcomes conducted by the World
Health Organization (WHO) shows a similar
correlation between lower reliance on neuroleptic
medication and recovery. Begun in 1968, this
research identified schizophrenics in nine
countries (China, Colombia, Czechoslovakia,
Denmark, India, Nigeria, USSR, United Kingdom, and
the U.S.) and tracked what happened to them over
the next five to ten years. The most striking --
some might say astounding -- finding was that the
patients from the three poorest countries -- India,
Nigeria, and Colombia -- fared far better than
their cohorts in the developed countries. Whereas
more than three-quarters of the Indians, Nigerians,
and Colombians were either recovered or doing
fairly well five years after their diagnosis, only
25 percent of the patients in the rich countries
enjoyed a similar level of
success.
Critics
of this study charged that it must have suffered
from design flaws. The patients from the poor
countries must not have been as sick. So the World
Health Organization launched another investigation,
making every effort to use the same criteria in
every country. It didn't matter. The new study
"replicated in a clear and, possibly, conclusive
way…the existence of consistent and marked
differences in the prognosis of schizophrenia
between the centres in developed countries and the
centres in developing countries," the authors
wrote. "It can now be said with a fair amount of
confidence that they are not the result of
differing sample composition in the two groups of
centres."
Muñoz,
the San Diego psychiatrist and former president of
the American Psychiatric Association, says he's
familiar with the study. He's a good friend of the
principal researcher. And Muñoz complains,
"No matter what the criteria were, you are not
comparing apples to apples.… To say that
American schizophrenics have a poorer prognosis is
just reading into the study things that the study
was not studying.… If we are going to try to
examine which country gets the best outcome, first
you have to know the country." Americans live with
a higher level of stress and more barriers to
success, Muñoz contends. "For example, if
someone is an anthropologist in Colombia, he's
probably employed and very successful. If he's an
anthropologist here, he's either dusting windows at
the museum or doing research that makes him famous.
Once you have a degree in this country, either you
belong to the minority that is very successful or
you will be unhappy for the rest of your
life."
Whitaker,
the Boston medical journalist who wrote Mad in
America, sees "an obvious flaw"
in the notion that cultural differences account for
the difference in outcomes spotlighted by the World
Health Organization study. "The poor countries in
the WHO studies -- India, Nigeria, and Colombia --
are not at all culturally similar," Whitaker argues
in his book. "They are countries with different
religions, different folk beliefs, different ethnic
groups, different customs, different family
structures." The developed countries studied also
share no common culture or ethnic makeup -- but
they do provide similar medical care. While in the
poor countries, "Only 16 percent of the patients
were maintained on neuroleptics. In rich countries,
61 percent of the patients were kept on such
drugs," Whitaker points out. "Certainly if the
correlation had gone the other way, with routine
drug use associated with much better outcomes,
Western psychiatry would have taken a bow and given
credit to its scientific potions.… Yet, in the
WHO studies, that was the model of care that
produced the worst
outcomes."
Today
the percentage of American schizophrenics taking
neuroleptic drugs is much higher. Mosher says, "The
standard practice is to treat all such persons with
one or another neuroleptic drug and to advise them
that they will need to take this drug for the rest
of their lives." Concurs Michael McDaniel, a San
Diego doctor who has practiced psychiatry for
almost 20 years, "You've got to be on the
medication. It's a mainstay of treatment." McDaniel
asserts that schizophrenics who go off their
medication have a relapse rate of 10 percent per
month. "So yeah, you've got to be on the
medication."
McDaniel
says he thinks that in most cases, the medication
alone is not sufficient. Most patients also need to
participate in a rehabilitation program. "The
studies all show that rehabilitation helps patients
coordinate the details of life." The local
psychiatrist adds that when the county surveyed
schizophrenia patients a few years ago, "The
number-one thing the patients wanted was individual
psychotherapy." However, few patients receive this,
according to McDaniel, who cites several reasons.
"One is the nature of the illness. People tend to
be erratic. They don't come to appointments
regularly. It's also partly historical. Time was
when schizophrenia was seen as a psychological
condition, and medicines were thought to be
bad.… You had people describing the
medications as chemical restraints." Today the
pendulum has swung too far in the other direction,
McDaniel says. "Now nobody really wants to talk or
listen to these folks." Economics adds one final
complication. "There's not a lot of money for
therapists.… It can easily cost $300 to $400 a
month for a single antipsychotic medication. And
people often take several. The fact is that MediCal
pays for medicines. But it pays very poorly for
psychotherapy. I don't know if there's a cause and
effect there. Probably there is."
McDaniel
estimates that as many as 95 percent of all
schizophrenic patients today are taking the newer
atypical neuroleptics, instead of the old-fashioned
varieties such as Thorazine. "The advances in the
medications are huge," he enthuses. Patients still
dislike taking them, and "They don't necessarily
work that much better. But they are a lot safer,"
he asserts. "And one of them -- clozapine --
probably is the best antipsychotic ever. It's in a
different category. It works in different parts of
the brain. The brain is enormously complex! It's
three pounds of electronic oatmeal." Every cell
connects to every other cell by as many as three
connectors. "So a certain amount of what goes on in
the brain has to do with timing. And there are wave
phenomena because the body releases different
chemicals at different times of the day and night.
Clozapine seems to work with the brain in that sort
of timed fashion. I think that makes a
difference."
McDaniel
acknowledges that even clozapine has some
drawbacks. In rare cases, "It can destroy someone's
bone marrow. So that means you have to check the
patient's blood count every two weeks. A lot of
people don't like that. Patients still get a lot of
other side effects. You have to take it more than
once a day. You feel sick. You drool all night. You
get sleepy," McDaniel says. "But when it works, it
works great! And for your really sick people with
schizophrenia, it's great."
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