Schizophrenia and Manic Depression share
Schizophrenia and manic depression could have similar genetic
causes, researchers suggest. The flaw appears to lie in genes
which affect how the central nervous system develops. Researchers
from the University of Cambridge say the findings are surprising
because the conditions are so different. Schizophrenia and manic
depression, or bipolar disorder, affect around 2% of the population.
The researchers looked at genes associated with the formation
of the myelin sheath which covers and protects nerves and enables
the efficient conduction of electrical impulses through the
nervous system. The genes were either linked to the development
of oligodendrocyte cells, which make up the sheath tissue, or
the development of the myelin itself. The team looked at mRNA,
which carries the genetic code, to look at how effectively the
genes were expressed in the different groups.
They found these genes were less active in people with schizophrenia
and bipolar disorder, and there were also faults in how the
remaining genes were expressed. Similar changes were seen in
the brains of people with both conditions. Treatment Dr Sabine
Bahn, who led the research, published in The Lancet, said: "We
believe that our results provide strong evidence for oligodendrocyte
and myelin dysfunction in schizophrenia and bipolar disorder.
"The high degree of correlation between the expression changes
in schizophrenia and bipolar disorder provide compelling evidence
for common pathophysiological pathways that may govern the disease
phenotypes of schizophrenia and bipolar disorder."
Writing in the journal, Dr Kenneth Davis of the Mount Sinai
School of Medicine, New York, USA, said: "The observation that
at least some myelin-related gene- expression deficits are common
between individuals with schizophrenia and bipolar disorder
is intriguing because schizophrenia and bipolar disorder have
different symptom profiles and require treatment based on quite
different neurotransmitter systems."
Psychiatric illness 'can be halted in
childhood' Source of Excerpt: Daily Telegraph Date: 16/07/2003
Up to half of all adult mental disorders could be prevented
if doctors tackled childhood psychiatric and behavioural problems,
according to a study published yesterday in the Archives of
General Psychiatry. A team of scientists studied 1,000 New Zealanders
for 15 years from the age of 11, and observed that the majority
of adults who have a psychiatric disorder had been diagnosed
with a psychiatric disorder in childhood. Adult anxiety and
schizophrenia-type disorders were preceded by a broad array
of juvenile disorders. Based on the findings, the report calls
for GPs to do more to screen for anxiety, depression, hyperactivity
and conduct/oppositional defiant disorder in children.
Schizophrenia drug claims questioned.
Scientists have raised concerns that claims about the benefits
of a new generation of drugs for conditions such as schizophrenia
may have been exaggerated.
Not only are the new antipsychotic drugs - known as atypicals
- thought to be more effective, they have also been associated
with fewer side effects. However, a new study has questioned
whether they are actually as relatively side effect free as
was thought. The drugs, which include risperidone, quetiapine,
clozapine and olanzapine, have been approved for use by the
NHS by the National Institute for Clinical Excellence (NICE).
However, they are very expensive, and campaigners are concerned
that they have only been made available to a small minority
of patients who would benefit.
The latest study has examined concerns that the drugs' reputation
for being side effect free is unjustified - largely because
initial trials compared them with a particularly potent older
generation drug called haloperidol. ] A team from Zucker Hillside
Hospital in New York lead by Dr Stefan Leucht carried out a
comprehensive review of data from 31 studies which involved
2,320 patients. Of the new generation drugs, only clozapine
was associated with fewer neurological side-effects and higher
efficacy than low-potency conventional drugs.
And as a group, new-generation drugs were only moderately more
efficacious than low-potency conventional antipsychotics. Dr
Leucht said: "If these findings are confirmed by future studies,
there would be a good argument for the use of appropriately
dosed conventional drugs - such as chlorpromazine - for patients
with schizophrenia in settings where new-generation drugs are
not generally affordable."
Marjorie Wallace, chief executive of mental health charity
SANE, expressed concern that the benefits of the newer drugs
was being questioned. She said: "All drugs, if they are to be
effective, will have side effects, but our experience is that
for the majority the side effects of the newer drugs are more
tolerable, people are more willing to take them and they are
therefore more effective. "In a significant number of cases
(by no means everyone) atypical drugs can transform lives in
a way in which the older drugs have failed."
Paul Corry, of the charity Rethink, said much more research
was needed before a switch away from the newer drugs could be
seriously considered. "People generally prefer the new atypical
antipsychotics because they are associated with fewer and less
severe side effects. "All medicines have side-effects of some
kind. They tend to be most severe when, as is often the case
with medicines for treating psychosis, they are prescribed without
the full involvement of the person taking them or above recommended
Experts See Mind's Voices in New
Light By ERICA GOODE, Excerpt from New York Times: May
It was just one voice at first, loud and male, coming from
the ceiling, saying, "Hi, John," calling him by name as
if they were buddies. But after a while, the voice, which
he came to know as the "evil genius," urged him to steal
other people's brain cells and told him that he had a cancerous
tumor in his head.
Eventually, other voices joined in, maybe 50 of them, male
and female, yelling "as loud as humans with megaphones,"
John recalled, from the moment he awoke in the morning until
he fell asleep at night, cursing or ordering him to kill
himself or, once, when he picked up a ringing telephone,
screaming in chorus, "You're guilty! You're guilty!"
"It was utter despair," John said. "I felt scared. They
were always around."
Auditory hallucinations are a hallmark of schizophrenia:
50 percent to 75 percent of the 2.8 million Americans who
suffer from the illness hear voices that are not there.
Like John, whose schizophrenia was diagnosed in 1981 and
who spoke on the condition that he not be identified, many
people with schizophrenia spend years pursued by verbal
tormentors as relentless as the furies of Greek mythology.
Suicide is sometimes the result, death seeming the only
escape from unending harassment.
Yet psychiatrists who study schizophrenia have traditionally
shown little interest in the voices their patients hear,
often dismissing them as simply a byproduct of the illness,
"crazy talk" not worthy of study.
Recently, however, a small group of scientists has begun
studying auditory hallucinations more intensively. Aided
by new brain imaging techniques, they have begun tracking
such hallucinations back to abnormalities in the brain,
finding that certain brain regions "light up" on brain scans
when patients are actively hallucinating. And the experts
are listening far more carefully to what patients say about
their hallucinatory experiences.
The research has led to new theories of what may cause
such bizarre alterations in perception and has spawned at
least one promising new treatment: the delivery of low-frequency
magnetic pulses to areas identified by the brain scans seems
to quiet, at least temporarily, the voices of patients who
have not found relief through standard treatment with antipsychotic
Ultimately, the researchers say, knowing more about what
causes auditory hallucinations may help them understand
more broadly the mechanisms that underlie schizophrenia
and other psychotic illness.
"These are critical, core experiences that really constitute
what having schizophrenia is all about," said Dr. Ralph
Hoffman, a psychiatrist at Yale who is studying the magnetic
stimulation treatment, called transcranial magnetic stimulation
In research described in a recent issue of Archives of
General Psychiatry, Dr. Hoffman and his colleagues found
that schizophrenic patients who received 132 minutes of
the magnetic stimulation over 9 days showed a significant
reduction in auditory hallucinations compared with control
subjects given a dummy treatment. Half of the subjects in
the study experienced a return of their symptoms within
12 weeks, though in some cases, the hallucinations remained
at bay for up to a year. All the patients were also taking
Schizophrenic patients describe voices that not only talk
to them but talk about them, haranguing, insulting and sometimes
provoking them to hurt themselves or to perform other actions.
In many cases, the hallucinations become more intense when
the patient is under stress.
In a study of 200 patients with schizophrenia and other
psychotic illnesses, Dr. David L. Copolov, director of the
Mental Health Research Institute of Victoria in Melbourne,
Australia, and his colleagues found that 74 percent said
they heard voices more than once a day. More than 80 percent
described the voices as "very real," rather than "dreamlike"
or "imaginary," and 34 percent experienced the voices as
coming from outside their heads (38 percent said they came
from both inside and outside their heads and 28 percent
from inside only).
A small minority of the patients said the voices they heard
were always or almost always supportive and positive in
tone. But more than 70 percent described them as always
or almost always negative. Dr. Hoffman of Yale said some
of his research subjects heard voices intermittently, but
others heard them continuously, the only respite coming
when they slept. One patient who committed suicide described
her voices as "a constant state of mental rape," Dr. Hoffman
Nicole Gilbert, 37, received a diagnosis of schizophrenia
in 1985. For years, she said, she could not read anything
because her voices "would tell me that it was about me."
"They would say things to try to make me believe that I
was Jesus," she recalled.
"Then they would torture me and say: `We're just joking.
You're so stupid, how could you believe this?' "
Ms. Gilbert, who is much recovered and is now a case manager
at a mental health agency in California, said the voices
seemed so real that she could not believe it when her friends
told her she was hallucinating.
The findings of studies using brain scanning techniques
like positron emission tomography (PET) or functional magnetic
resonance imaging (M.R.I.) underscore how persuasive auditory
hallucinations are to those who experience them. When patients
are hallucinating, areas of the brain involved with auditory
perception, speech, emotion and memory show increased blood
flow, indicating greater nerve cell activity.
"These people are not just crazy; they're telling you what
their brains are telling them," said Dr. David Silbersweig,
an associate professor of psychiatry at Weill Medical College
of Cornell University who has studied hallucinations with
brain-imaging. Still, studies so far have come up with differing
patterns of brain activation. For example, both Dr. Hoffman's
group and a team led by Dr. Philip McGuire, a professor
at the Institute of Psychiatry in London, found heightened
activity in Broca's area, a region of the frontal lobe involved
with speech perception and processing. But Broca's area
was not identified in Dr. Silbersweig's research or in a
study by Dr. Copolov that will be published soon. The precise
areas of the brain's temporal and parietal lobes that show
activity during hallucinations also differ from study to
The discrepancies are difficult to interpret and reflect
the imprecision of even advanced technology in capturing
highly complex brain processes. The data are further clouded
because the high costs of scans limit the size of most studies.
But the disparity in the findings has also led to different
theories about how hallucinations arise.
Schizophrenia typically strikes in adolescence or early
adulthood. Extensive research over the last few decades
has indicated that the brains of people with the illness
differ in significant ways from those of healthy people.
Experts agree that schizophrenia stems from a combination
of genetic predisposition and unknown environmental influences.
What everyone who studies hallucinations agrees on is that
schizophrenic patients misperceive signals generated inside
But scientists are still debating what is being misinterpreted
and how this occurs. Dr. Copolov, for example, suggests
that the "voices" patients hear are really fragments of
auditory memories "that come to consciousness fused with
emotional content" and are then incorrectly evaluated as
originating from an outside source.
The fact that in some studies the hippocampus and other
brain structures known to be involved in memory retrieval
are active during hallucinations is consistent with this
theory, Dr. Copolov said. Other researchers, including Dr.
McGuire of the London institute, have argued that what is
misperceived is internal speech - the running dialogue most
people engage in while thinking. In schizophrenia, in this
view, a mechanism that normally distinguishes between internal
and external speech breaks down.
Dr. Judith Ford, an associate professor of psychiatry at
Stanford, and Dr. Daniel Mathalon, an assistant professor
of psychiatry at Yale, have proposed that the brain's auditory
cortex may play a role in this failure to identify speech
correctly as internal or external. In studies, they recorded
electrical activity in the auditory cortices of schizophrenic
patients and healthy control subjects. In the control group,
the auditory cortex showed a dampening of activity in response
to internal speech, they found. But this inhibition was
lacking in schizophrenic patients.
"When you and I have these thoughts," Dr. Ford said, "we
are inhibiting the response of our auditory cortex, saying,
`Don't pay attention to this; it's me, talking.' But the
schizophrenic patients do not inhibit the response the way
normal healthy people do."
Dr. Hoffman has a slightly different theory. In schizophrenia,
he suggests, a loss of gray matter may intensify the link
between Broca's area, involved in speech production, and
Wernicke's area, responsible for speech perception.
In the normal course of affairs, Dr. Hoffman said, Wernicke's
area receives information from a variety of nearby brain
areas and distant structures like Broca's. But in schizophrenic
patients, who in imaging studies show a loss of gray matter
in the superior temporal lobe containing Wernicke's, the
signals sent from more local regions may be knocked out
or greatly decreased. If so, Dr. Hoffman suggests, the signals
coming from Broca's may then become more salient, bombarding
Wernicke's area with internally generated words and phrases
that are in some way interpreted by Wernicke's as external
Dr. Hoffman noted that transcranial magnetic stimulation
applied to Wernicke's area appeared to suppress hallucinations
in some schizophrenics. "My view is that in schizophrenia
it is not just inner speech or an acoustic memory that is
misinterpreted," Dr. Hoffman said. Instead, he said, patients
"are actually having perceptual experiences that have the
same clarity and vividness of external speech."
Dr. Hoffman's research team is now using M.R.I. scanning
with each research subject to determine which brain regions
are active when the subject is hallucinating, and then delivering
stimulation to that area.
But whatever the research on magnetic stimulation yields,
it is already helping some of the 25 percent of hallucinating
patients whose voices are not stopped by antipsychotic drugs.
"Just stimulating in a single site appears to have a significant
impact," Dr. Hoffman said.
Other experts call the results impressive.
In the treatment, an electromagnetic coil shaped like a
Figure 8 is held to the patient's head. The coil produces
a quarter-size magnetic field that is then rapidly turned
on and off, inducing an electrical field in the cerebral
cortex's gray matter. Scientists do not know exactly how
the treatment works, but they believe it dampens the reactivity
of neurons, an effect that is then passed on to other connected
Unlike electroshock therapy, long used for severe depression,
transcranial magnetic stimulation does not induce seizures
at the levels used in the studies and has a far more selective
effect on the brain. Nor does the treatment appear to have
the serious side effects, like memory loss, of electroshock
The most common side effect, Dr. Hoffman said, is mild
contractions of the scalp that some patients find uncomfortable.
Also, in contrast to electroshock, patients receiving the
magnetic stimulation remain awake, unsedated, through it.
John, who participated in Dr. Hoffman's research last summer,
said the procedure did not bother him. "This thing kind
of taps on your head every second and it's not intrusive,"
John said. He said his voices got "smaller and not as loud"
after treatment, but they did not go away entirely, and
the improvement lasted only six months.
Without a full cure in sight, John said he has developing
his own tactics for fighting the hallucinations, which persist
despite the medications he takes. He talks back to them
in his head, he said, and criticizes them when they criticize
him. Between his own efforts and the treatments, John has
made much progress. He now attends school, has his own apartment,
goes out with friends and has a girlfriend. "I wanted to
try to make the voices my friends, but I found out later
that that is not realistic," John said. "I was kicked around
by them for a long time. Now, if they start bothering me,
I just kick them around instead."
Survey Finds U.S. Has High Rate Of
Mental Illness, Low Rate Of Treatment Compared To Other Countries
BOSTON, MA -- Source: Harvard Medical School Date: 2003-05-07.
The United States has a higher prevalence and lower treatment
rate of serious mental illness than a number of other developed
countries, according to a study published in a special edition
on international health care in the May/June issue of the policy
journal Health Affairs.
Treatment was also to be more strongly related to the ability
to pay and less to need for care in the United States than the
other countries. The study analyzed data from community surveys
with more than 22,000 respondents in Canada, Chile, Germany,
the Netherlands, and the United States. All these countries,
except the United States, have universal health insurance.
Despite differences in treatment, researchers found remarkably
similar high proportions of the population with mental disorders
(17 to 29 percent), early age of onset (mostly in childhood
through the early adult years), high rates of chronic mental
illness, and high levels of adverse effects on jobs, marriages,
and other aspects of life, said corresponding author Ronald
Kessler, professor of health care policy at Harvard Medical
School's Department of Health Care Policy.
"The consistency of these patterns across a wide variety of
countries is striking," Kessler said. "Issue number one is that
we can't wait as long as we do to get young people into treatment.
Issue number two is that we have to do a better job of making
sure patients are treated with the best available therapies
once we manage to get them into treatment."
In all countries, young, poorly educated males with serious
mental disorders are the least likely to receive treatment.
The report suggests that school-based interventions in low-income
school districts may help reach these young men to prevent progression
from mild to more serious disorders. Early intervention is uncommon
but important, according to the report.
"People with mild mental disorders, if left untreated, have
a significant risk of future serious outcomes, such as attempted
suicide, hospitalization, and work disability," the authors
"Most people with serious mental disorders have conditions
that start in childhood or adolescence, but do not get treatment
until adulthood," Kessler said. "The problems are usually quite
serious by the time they go for professional help. In many cases,
these people have dug themselves into quite a hole before getting
treatment that would be difficult for even the most emotionally
secure person to overcome, such as teen childbearing, school
failure, violent relationships, and drug problems.
We can't wait as long as we currently do to get these kids
into treatment." People with more serious disorders were more
likely to receive treatment, but between one-third and two-thirds
of people with serious disorders in the five countries reported
receiving no treatment.
No matter how mild or serious the mental disorder, people were
more likely to receive treatment if they were older (except
for Chile), educated, and female. Kessler said he and his co-authors
were also struck by the inadequate treatments in this country.
"This involves both medical care that fails to conform with
accepted treatment guidelines, such as a homeopathic dose of
a psychopharmacological medication prescribed by a family doctor,
or care in some other sector of the treatment system, such as
self-help or religious counseling, that has not been shown to
be effective in treatment clinically significant mental disorders."
The instrument used to assess mental illness in the surveys,
the Composite International Diagnostic Interview (CIDI), was
developed in 1990 by the World Health Organization (WHO). Kessler
conducted one of the first major CIDI surveys, a nationally
representative general population survey of the United States.
When he became the chair of the WHO CIDI Advisory Committee
in the late 1990s, Kessler established a data pooling project
for cross-national comparative studies that led to this paper.
"The first generation of CIDI surveys focused on diagnoses,
but did not have good information on severity, which can vary
enormously," Kessler said. Severity estimates in this paper
Kessler is one of two coprincipal investigators of an expanded
survey, called the WHO World Mental Health survey initiative,
which is being carried out in 28 countries with a combined sample
size of more than 200,000 respondents. Analyses of the new surveys
are beginning this year, Kessler said. Source: http://www.sciencedaily.com/releases/2003/05/030507080958.htm
Glaxo Wins FDA Approval For New Version of Wellbutrin -- GlaxoSmithKline
PLC said Friday that U.S. regulators approved Wellbutrin XL,
a new version of a GSK antidepressant whose earlier forms have
been threatened by generic competition. The U.S. Food and Drug
Administration approved Wellbutrin XL for treatment of major
depressive disorder in patients aged 18 or over.