Schizophrenia 'may be many diseases'
Saturday, 26 October, 20
Schizophrenia may be an array of different disorders rather than one
single disease, doctors believe. Research carried out in the United
States suggests there could be at least three different types.
Doctors suggested the finding could help to dramatically improve their
understanding of schizophrenia and help in the development of new drugs
to fight the disease.
Dr Bruce Turetsky and colleagues at the University of Pennsylvania
compared symptoms and brain patterns in 116 people with the disease
and 129 healthy people. Both groups were assessed using the California
Verbal Learning Test which examines learning and memory skills and their
recall ability. They also underwent scans to examine the physical make-up
and chemistry of their brain.
The tests revealed three distinct types of schizophrenia.
In the first group, parts of the brain called temporal lobes were smaller.
They also transmitted fewer chemicals in these areas, which are linked
to language and memory. They had problems paying attention, organising
their thoughts and expressing ideas in a logical and coherent way.
They were mostly young males who had been diagnosed with schizophrenia
at an early age. It affected almost one in five of those with the disease
involved in the study.
In the second group, doctors discovered changes in the frontal-striatal
region of the brain. They had less grey matter in the frontal lobes
and had enlarged ventricles. This area affects cognition and motor function.
Their temporal lobes were normal.
Almost one in three of those with the disease who were involved in
the study fitted into this category.
More than half of the remaining patients had mild memory problems.
Damage to their temporal lobes or frontal lobes was not as great as
those included in the other two groups.
The doctors suggested that their findings may explain why a broad range
of symptoms can be diagnosed as schizophrenia.
They added that their study may also indicate why scientists have found
it difficult to identify the causes of the disease - particularly if
they believe it is just one disease.
Dr Turetsky said: "One of the reasons we haven't been successful
in identifying 'the cause' of schizophrenia may be because we are studying
mixed groups of individuals who don't really have the same thing wrong
He added: "Our results indicate that there are different neurobiological
profiles associated with different presentations of schizophrenia. We
may be dealing with more than one disease."
The researchers are now planning to expand their study to find out
if differences in the brains of patients remain the same throughout
The study is published in the journal Neuropsychology which is published
by the American Psychological Association.
For more information see: http://www.apa.org/releases/schizophrenia.html
A Hopeful Voice - A powerful,
first-person account describes one man's three-decade struggle with
and eventual recovery from schizophrenia; The Day the Voices Stopped;
A Memoir of Madness and Hope; Review
BYLINE: ANNIBALI, JOSEPH
Joseph Annibali, M.D., has a private practice of psychiatry and psychoanalysis
in McLean, Virginia.
If you want to journey inside a mind tormented by schizophrenia, read
The Day the Voices Stopped. As William Styron did for severe depression
in Darkness Visible, and Kay Redfield Jamison did for manic depression
in An Unquiet Mind, coauthors Ken Steele and Claire Berman have written
a firsthand account of Steele's three-decade struggle with chronic schizophrenia
and his remarkable recovery when a new medication stopped the hallucinatory
voices. After his condition improved dramatically, Steele devoted himself
to improving the plight of the severely mentally ill, becoming a nationally
recognized advocate. He intended that this story of courage and recovery
would give hope to those who suffer from similar illnesses. Although
this is a remarkable book, I believe that it is overly optimistic about
the current prospects for recovery from severe mental illnesses such
Ken Steele, an apparently normal boy in a blue-collar family in Connecticut,
was fourteen when his auditory hallucinations started, without warning.
He began to hear insistent, taunting voices, commanding him to kill
himself: "Hang yourself," they told him. "The world will
be better off. You're no good, no good at all." Through nearly
250 pages Steele assaults the reader relentlessly with descriptions
of the voices that commanded and taunted him. Together with other descriptions
of his suffering, the impact is at times mind numbing. Not until near
the end of the book (and his life), when new medication finally helped
him, is Steele given more than a moment's respite.
The Day the Voices Stopped straightforwardly presents his deteriorating
world and descent into psychosis. At first he began to have difficulty
differentiating what was happening outside himself from what was happening
within. For example, at times he perceived his voices as coming from
the television. During his mother's pregnancy he believed that his unborn
brother was speaking to him directly from her womb. He became isolated
from friends and family.
Eventually, in response to the continued self-destructive demands of
the voices, he attempted suicide for the first of many times. Denying
the illness, Steele's father refused to allow his son to be hospitalized.
Steele's condition continued to deteriorate. Though he was unusually
bright and loved reading, he dropped out of school. Tension with his
father increased. Needing to get away but still very ill, at age seventeen
Steele left home for New York City, never having visited there before
and without a job. It's rather obvious that he was trying to escape
his family, who could neither understand nor help him.
New York City is no escape
Not surprisingly, soon after arriving in New York, he met a helpful
stranger who turned out to be a homosexual predator and pimp. Steele
was exploited sexually and began working as a hustler. When the voices
commanded him to commit suicide by jumping off a tall building, he was
apprehended by the police and sent to the first of many state hospitals.
There are numerous heartrending reports of the well-intended but often
horrendous treatment in these facilities. On page after page Steele
describes months of seclusion, restraint, and horrible medication side
effects. In one hospital, he was attacked by other patients, bound,
gagged, and raped by several men. His injuries in this attack were so
severe that he needed major surgery.
Many readers will react with sorrow and despair to the descriptions
of Steele's illness, his apparent inability to get good, consistent,
helpful mental health care, and the reports of frank neglect and even
abuse at the hands of those who were supposed to be his caretakers.
He often felt alone and abandoned, at times living as a street person.
His parents never visited him in the hospital. He became more and more
depressed, went in and out of various hospitals, suffered severe side
effects from antipsychotic medications, and wandered from city to city,
all across the United States. The pattern he reports in each location
was similar: When his psychosis flared up, he would be hospitalized
against his will. He would be forced to take medication that was ineffective,
which would be followed by severe side effects, and he might be assaulted
by staff, patients, or the police. Often he returned to the streets,
living as a homeless person, working now and then as a prostitute. Depression
and suicide were companions as dependable as his ever-present voices.
Steele states that living on the street often was preferable to being
treated in deplorable state facilities. He comments that some staff
members were dedicated to keeping patients hospitalized indefinitely
as a means of retaining their jobs. He also reports that the hospital
staff encouraged ethnic tension, often leading to violence.
Eventually, Steele found that alcohol muffled his voices, but he drank
excessively and became addicted to alcohol. His overall health deteriorated.
Heavy smoking took a toll on his lungs; he developed severe asthma and
required treatment with steroids. While improving his breathing, the
steroids caused his weight to balloon to more than four hundred pounds.
The obesity precipitated severe sleep apnea. Eventually, Steele's psychiatric
disability was joined by a physical incapacitation. He could hardly
Recovery on Risperidone
Ultimately, Steele came under the care of a good therapist, who referred
him for a psychiatric consultation. The psychiatrist placed Steele on
Risperidone, one of a new generation of antipsychotic medications. His
voices ceased for the first time, after more than three decades as unwanted
residents of his psyche.
Steele's descriptions of the challenges he faced as he recovered are
poignant. Initially, he was confused as he struggled to make sense of
the voices' disappearance. He lamented their loss, wished for their
return, even felt abandoned. At other times, he worried that the voices
were tricking him, lying in wait to catch him off guard. He felt bombarded
by the everyday noises that they previously had masked.
After the voices stopped, Steele was aware that people saw him as a
grown man but that he felt like a child. Ordinary tasks, such as organizing
his kitchen, were great challenges. Steele writes with authority about
the pernicious effects of chronic dependency on the mentally ill: "Things
that most people pick up through life experience have to be taught to
those of us whose primary residence, for years, has been our inner world.
When we reenter 'the real world,' it's like stepping into foreign territory."
The freedom feels threatening: "During the first few months of
being well, many people who have suffered from hallucinations quickly
get unwell. System addiction is often the cause. It needs to be recognized
so that it can be addressed and combated."
Work as an activist
An important part of Steele's life story is his long-standing interest
in and involvement with community activities to benefit the mentally
ill. Even before his recovery, he was appointed to and served on panels
and advisory committees in Hawaii and San Francisco. In New York City
he started a voter empowerment project for the mentally ill population.
Once he recovered on the Risperidone, as Steele writes, "I vowed
that I would use my own voice, in whatever ways I could, to make life
better for myself and others who struggle, each day, to survive schizophrenia,
and other devastating diseases of the mind. I would listen to, and learn
from, the voices of other mentally ill people and their families. Working
together, we could make a difference. And we would be heard."
Steele took over as editor of a mental health newsletter and renamed
it New York City Voices: A Consumer Journal for Mental Health. "My
hope was that voices could now become a positive noun--one that clarifies
distortion instead of the other way around," he writes. The newsletter
has informed readers about political and legislative issues, such as
parity legislation. Additionally, it has printed individual stories
about recovery and empowerment. Writes Steele: "I strongly believe
that recovery and empowerment are possible for everyone with a mental
illness, which is why it is important for us to reach out to one another
with information and strategies for coping in the world of the 'normals.'
In response to many requests for assistance that were pouring into
New York City Voices, Steele started an information and referral service.
He began to speak about mental illness and recovery before lay and professional
groups and started a recovery support group that met in his home, noting
that the group filled his own need for support as well as the needs
of others. He spoke around the country, spreading the message that "recovery
from mental illness is possible and that people suffering from mental
illness need to be understood and assisted, not feared and avoided."
The New York Times ran a front-page story about him in early 1999. With
his therapist, he appeared in a Voice of America broadcast that brought
in requests for information from all around the world.
Steele fought stigmatization and injustice in the treatment of the
mentally ill. He writes: "There are now far more mentally ill people
in the nation's jails than in state hospitals--people arrested for shoplifting,
intoxication, fare-beating, living on the streets. More than 300,000
mentally ill people are in our jails and prisons, five times as many
as are being treated in our state hospitals. Many would never have been
incarcerated if there had been adequate community caring ... and care."
A vision of the future
He ends the book with this quote: "I have a vision that goes like
this: In a new century, mentally ill people will have the science, the
organized voting strength, and the means to leave our ghettos of isolation
behind us. We will finally join with the mainstream community, where
we'll be able to live as independent individuals and not as a group
of people who are known and feared by the names of our illness."
Unfortunately, Steele's vision will be difficult to attain. He is correct
in claiming that society views those who are mentally ill and homeless
as a "throwaway population." Society seems unwilling to devote
adequate financial resources toward caring for the severely mentally
ill. Fairfax County, Virginia, where I live and practice, tops many
lists as being the wealthiest county in the United States. Yet, I know
firsthand from my work in mental health centers here that funding is
inadequate, waiting lists can be long, and patients are often forced
into group treatment because groups are cheaper than individual care.
Also, not every patient responds as positively as Steele did to the
newer antipsychotic medications. Just recently, we have been learning
that these medications may have serious side effects that previously
were not well known. Many of these newer drugs are quite expensive and
may not be covered by managed care. The patients who need them the most--those
chronically disabled by psychiatric illness--are the very ones who are
not working and lack the resources to pay for these drugs. Our society
cannot legally force treatment on most severely ill people unless they
are imminent dangers to themselves or others. Sadly, their illnesses
often distort their thinking, making them run away from treatment. Many
"street people" are severe mentally ill and refuse treatment
for their illnesses.
As a practicing psychiatrist, I believe that the book's description
of Steele's illness is one-dimensional. By the authors' report he was
diagnosed with schizophrenia, and I accept this diagnosis. Schizophrenia
is not just about auditory hallucinations, however. There typically
are accompanying signs of psychotic illness, such as difficulties with
thinking, delusions, and so-called negative symptoms. Although these
other symptoms are alluded to, an unsophisticated reader might be left
with the impression that the essence of schizophrenia is auditory hallucinations.
This is not necessarily true. And if I may be permitted a quibble, the
title of the book, The Day the Voices Stopped, while catchy and evocative,
is misleading. Most of the book is about the periods before and after
the cessation of voices, not the "day" referred to in the
Also, for the sake of balance, I need to mention that Steele and Berman
present a one-sided view of treatment in state hospitals. The authors
may give the uninitiated reader the impression that all state mental-
health institutions are snake pits, run by venal individuals who are
unconcerned about the welfare of their patients. I will acknowledge
that there are some less-than-stellar facilities in this country, but
most are not as bad as the book may imply. Furthermore, Steele does
not emphasize enough that severe psychotic states often lead to perceptual
distortions and resulting behaviors that predispose these individuals
to the kinds of bad experiences he reports. When an individual with
such predispositions enters an overworked and understaffed legal or
mental health system, the results can sometimes be tragic. If accurate,
there is no justification for the abuse and neglect that he describes.
Still, it is not just a bad mental health system but these illnesses
themselves that contribute to unpleasant and unfortunate treatment experiences
like Steele reports.
Additionally, the point of view presented lacks a sense of the emotional
complexity and nuance that exists in human life. If we lack a complex
view of the psychic functioning of humans--individually and in groups--we
cannot understand why human conflict is so universal. It is typical
of individuals, when they come together as groups and even societies,
to regress, to view the world in simple black-and-white terms, as all
good or bad. This is a primary cause of racism, religious intolerance,
and discrimination in general. Those groups discriminated against, whom
we exclude and extrude, typically are those "different" from
the rest of us. To put it simply, we want to get rid of those who are
different from us. We even need groups who are different from us, and
the mentally ill easily fall into that category. This universal human
tendency, which the book does not acknowledge, will be a fundamental
impediment to attaining Steele's vision.
The need for care and support
Despite these drawbacks, I know of no other book that so intimately
portrays the day-to-day, moment-to-moment, reality of someone who has
been hallucinating for so many years. For this description we should
be grateful to the authors. Also, Steele and Berman provide an equally
compelling account of the nature of treatment in the state hospital
system, where many patients like Steele end up. While my own professional
experience suggests that their descriptions of deplorable institutional
treatment are not universally applicable, the pictures they paint are
ugly, and we need to look at the situation with our eyes wide open.
Further, Steele writes thoughtfully about the problems of dependency
that eventually trap these chronically ill, severely disturbed, patients
in a web of poor functional capacity from which there is no escape.
Finally, he writes movingly about the role of social support in recovery.
I recall during my own psychiatric training that an eminent senior psychiatrist
said that the best thing we could do for many of our most severely disturbed
patients was to send them to an Alcoholics Anonymous meeting, whether
or not they were alcoholics. He thought that the social support people
get in AA was more helpful and powerful than the drugs and other treatments
we then had available.
Steele did accomplish much, but he died of cardiac failure on October
7, 2000, just prior to his fifty-second birthday. Sadly, his new voice,
of determination, dedication, and self-possession, was silenced when
he had much left to say. Steele was a man on a mission, a man with a
prophecy of hope and recovery. We need prophets: they show us where
to aim as individuals and as a society. I hope that he will not have
been a lone voice crying in the wilderness. His book will give hope
to those who suffer from serious mental illness.
Some individuals and their families who read this book will be disappointed
because they cannot and will not recover to the extent that Steele did.
The problems they (and we) face in combating these serious conditions
are complex. In my professional experience, there are no easy answers.
In the future, Steele's belief--that all who suffer from severe mental
illness can recover as he did--may be borne out. In the meantime, the
severely mentally ill will benefit through the social and political
empowerment that he advocated. Moreover, we all will benefit from his
reminder that when patients are under the care of professionals, the
professionals really ought to care. In our fast-paced world of managed
care and managed everything, caring is often lost.
Australia Scientists Identify Schizophrenia
Tue Nov 26, 2002
An Australian research team said on Tuesday it had identified 153
genes affected by schizophrenia in a step toward discovering the causes
of the illness.
The 153 affected genes were identified after completing high-throughput
screening of 12,000 genes in post-mortem studies of brain tissue from
The research team at the institute's Rebecca Cooper Laboratories outlined
its plans to identify the core genes to the Australian Health and Medical
Dean said general current thinking is that genetics plays a major role
in the development of schizophrenia, but studies with the identical
twins of sufferers suggest there must also be another factor that brings
on the disease.
Israeli Biotech: Schizophrenia Associated
With the COMT Gene
IDgene Pharmaceuticals (Jerusalem) says it has discovered an association
between the COMT (catechol-O-methyltransferase) gene and schizophrenia.
The details of this finding will be published in next month's issue
of The American Journal of Human Genetics and are now available online
"The genetic basis of schizophrenia is poorly understood and the
data presented to date has been mostly inconclusive. IDgene has successfully
produced the most statistically significant results ever reported in
schizophrenia or in any other common polygenic disease. The study shows
that the COMT gene may account for more than 20% of all schizophrenia
patients. In the near future, we expect several additional discoveries
of novel disease susceptibility genes, as well as genes responsible
for variation in drug response," notes IDgene's CEO, Ariel Darvasi.
University Of Toronto , 11/13/2002
Gene Increases Schizophrenia Risk, Says Study
Scientists at U of T have discovered the first "risk gene"
for schizophrenia found in the general population.
An uncommon variation of a gene called Nogo, when inherited from both
parents, increases the risk of developing schizophrenia, says a study
to be published in Molecular Brain Research Nov. 15. Previous findings
about other risk genes for the disease were restricted to specific ethnic
"Finding a risk gene in the general population - the first finding
of this type internationally - opens the door to discovering new and
related risk genes. Now scientists will know where to look for related
genes," says pharmacology and psychiatry professor Philip Seeman.
"This will help in diagnosis and potentially in the design of new
medications for treatment of this terrible disease," adds Seeman
who worked on the study with psychiatry professor Teresa Tallerico,
lead author and pharmacology graduate student Gabriela Novak and undergraduate
student David Kim.
The study shows that one in five people with schizophrenia has this
risk gene. Researchers found that 17 of 81 individuals with schizophrenia
- 21 per cent - had inherited the uncommon Nogo variant gene from both
parents. In a control group of individuals without schizophrenia, only
three per cent had inherited the gene from both parents. People can
inherit the variant Nogo gene from just one parent but there's a schizophrenia
risk only when this gene is inherited from both parents. The gene does
not suggest a diagnosis for schizophrenia but rather an increased predisposition
to the illness.
One of the Nogo gene's functions is to produce proteins that inhibit
the growth of nerve endings in the brain. Unlike the common form of
Nogo, the variant gene has three extra chemical bases, known as CAA,
in a region of the gene that regulates protein production. The researchers
found that activity of the Nogo genes was higher in the post-mortem
brain samples of individuals with schizophrenia. It is possible that
these extra CAA bases lead the variant Nogo gene to produce more proteins,
thereby reducing the number of nerve endings in regions of the brain
associated with schizophrenia symptoms, Seeman says. However, more research
is needed to confirm this.
"This study adds to the rapidly evolving theory that, in the brain
of those who suffer from schizophrenia, the nervous system develops
in a slightly altered fashion leading to the onset of symptoms such
as hallucinations and delusions in young adulthood," says Seeman.
Although the cause of schizophrenia is not known, the treatment of
the symptoms has been well-established since the 1970s. Antipsychotic
medication is used to block the action of dopamine, an adrenaline-like
chemical transmitter in the nervous system that becomes overactive in
people with schizophrenia.
"This finding of a risk gene in the general population could lead
to the development of medications outside the dopamine system, perhaps
targeting the protein produced by the gene," suggests Seeman.
The study was supported by the National Alliance for Research on Schizophrenia
and Depression, the Eli Lilly Research Fellowship in Women's Mental
Health, the Stanley Foundation Scholars Mentors Program of the National
Alliance for the Mentally Ill, the Canadian Institutes for Health Research,
the Ontario Mental Health Foundation and the National Institute on Drug
Abuse. Professor Tallerico is an Essel Investigator of the National
Alliance for Research on Schizophrenia and Depression (NARSAD) and Professor
Seeman is a Janice Lieber Investigator of NARSAD.
The University of Toronto, Canada's leading research university with
60,000 students, is celebrating its 175th anniversary in 2002.
Schizophrenia drugs linked to diabetes
HALIFAX - Some doctors are warning about a class of anti-psychotic
drugs linked to life-threatening side effects.
Health Canada has received reports that Zyprexa is suspected as the
cause of four diabetes-related deaths. The drug was approved for use
in Canada in 1996 and is made by Eli Lilly.
Zyprexa is part of a new class of drugs called atypical anti-psychotics.
A growing number of schizophrenics in the country are using the new
drugs, such as Clozaril. There are 300,000 schizophrenics in Canada.
People with schizophrenia experience three major types of symptoms:
- psychotic symptoms: delusions and hallucinations
- deficit symptoms: diminished emotions, social withdrawal and low
- mood symptoms: depression to suicidal
"It helps me by calming me down because I'm also nervous, my legs
shake and my hands tremble," says Richard Thompson of Edmonton
who has gained more than 30 pounds (14 kg) and developed diabetes since
taking the drugs. His doctors believe the drug is at least partly responsible
for his weight gain.
The most common side effects associated with Zyprexa are:
Less common effects include skin rash, depression, fast heart rate
Other known, but less common, effects are listed as: skin rash, headache,
depression, fast heart rate, constipation and weight gain.
Research published in the British Medical Journal and other journals
suggest atypical anti-psychotics can cause diabetes.
those drugs interfere with some kind of chemical
processes both in the brain and body and lead to the development of
something called insulin resistance," says Dr. Pierre Chue, Thompson's
doctor. "As that develops, the diabetes sets in."
Health Canada has received four reports of diabetes-related Zyprexa
deaths over five years.
Two of those deaths involved teenage boys who fell into diabetic
In the U.S., the government has collected reports of 140 people who
developed diabetes after taking Clozaril.
The companies which make the drugs say people with schizophrenia
tend to have unhealthy diets which put them at risk of getting diabetes.
Marie Josee-Poulin, a psychiatrist at Laval University in Quebec,
says the evidence linking the drugs to diabetes isn't clear yet but
she says the concerns are justified.
A Health Canada newsletter has warned doctors that atypical anti-psychotics
may be associated with new cases of diabetes. Some doctors would like
to see this as a clear warning on the label.
Both Poulin and Chue says too many doctors are unaware of the risks
and side effects of the new class of anti-psychotics. They say patients
should be closely monitored for signs of unstable blood sugars or
Written by CBC News Online staff