Faulty
wiring in the brain may cause early-onset schizophrenia
CHICAGO Using diffusion tensor imaging (DTI) to
look into the brains of children with schizophrenia, researchers
have discovered abnormalities in the white matter of the
frontal lobe that disrupt the transmission of signals regulating
behavior, according to a study presented today at the 89th
Scientific Assembly and Annual Meeting of the Radiological
Society of North America (RSNA).
"Until now there's been no sophisticated method of
finding abnormalities in the white matter of the brain,"
said the study's lead author Manzar Ashtari, Ph.D., associate
professor of radiology and psychiatry at North Shore-Long
Island Jewish Health System and Albert Einstein College
of Medicine in New York. "Conventional magnetic resonance
(MR) imaging is limited in its ability to reveal brain myelination,
but DTI enables us to measure the myelination process."
Myelin is the covering of nerve bundles that protects neurons
and increases their transmission efficiency. The accumulation
of myelin around these neurons is called myelination. In
the human developmental process, myelination correlates
with maturing patterns of behavior. In patients with schizophrenia,
the cells that carry out the process of myelination are
defective.
Myelination activity is at its strongest during the teen
years. "This is a critical time for adolescents who
are still maturing emotionally," Dr. Ashtari said.
"During the myelination process, microstructural damage
to developing white matter fiber tracts may lead to developmental
abnormalities. These are the types of abnormalities we observed
in the frontal white matter regions in the children with
schizophrenia."
Dr. Ashtari and her team used DTI to study 12 adolescents
with early-onset schizophrenia and nine healthy, age-matched
adolescents. They found distinct differences in the white
brain matter of the frontal lobe, which controls numerous
emotional, cognitive and linguistic behaviors. When signals
are disrupted, abnormal behaviors result. "It's a problem
with connectivity," Dr. Ashtari said. "It's like
the wiring in a house, only we are looking at the network
of the brain--how the brain is wired."
"Early-onset schizophrenia is especially disheartening
because so many of these teens aren't diagnosed until they're
adults," Dr. Kumra said. "Because these patients
develop the disease at an early age when they have not yet
built their lives, they tend to have a worse prognosis than
those who have adult-onset schizophrenia."
Dr. Ashtari hopes that further DTI studies will yield more
insight into the inner workings of schizophrenia. "If
the malformation in the myelination process is the cause
of schizophrenia, future special efforts can be focused
in production of therapeutic agents that speed up or restart
the myelination process," she said.
Co-authoring the study with Drs. Ashtari and Kumra are
Marjorie McMeniman, Ph. D., Joshua Vogel, Alan Sloan Diamond,
M.D., and Philip Szeszko, Ph.D.
Drug Implant Offers New
Hope for People with Schizophrenia
By Ellen Barry, Globe Staff, 9/26/2003
PHILADELPHIA -- Researchers said yesterday that they are prepared
to seek FDA approval of a surgically implanted tablet that could deliver
daily doses of psychiatric medication for as long as a year.
The implants might revolutionize treatment of chronic mental illnesses
like schizophrenia, which now require patients to take daily cocktails
of powerful medications.
For some, the implant of haloperidol, a powerful antipsychotic drug,
promises to stop the destructive spirals of psychosis that occur when
patients stop taking medication because of side effects, logistical
barriers, or lapses in memory. But patients' rights advocates say
that implants of psychiatric medication would give the state coercive
power unmatched since the age of the lobotomy.
Dr. Steven Siegel, the University of Pennsylvania researcher who
is leading the development of the implant, gathered with advocates
yesterday to debate its impact on the rights of people with mental
illness.
"This is very doable technology," said Siegel, director
of the Stanley Center for Experimental Therapeutics in Psychiatry.
"It's not the science that is limiting. If there really is interest,
then I think drug companies and other groups" would be happy
to move forward with implants.
The implant consists of a biodegradable polymer disk about 1 centimeter
in diameter and 1 millimeter thick, which would be inserted during
a 15-minute outpatient surgical procedure, he said.
The disk, which could also contain antidepressants or other medications,
gradually disappears over the course of a year, slowly releasing the
drug as it dissolves.
If the patient needed to be taken off the drug, its effects would
immediately cease when the tablet was removed, Siegel added. Currently,
the nearest alternative is an antipsychotic injection, which is not
reversible and lasts for only a month.
Siegel said he envisions that the implant would be used only on a
voluntary basis, by people who have made the decision to accept medication
for a year.
But Jonathon Stanley, a lawyer and activist whose parents founded
the Stanley Foundation after he became severely psychotic as a young
man, said he sees the implant as useful only for people who refuse
medication.
"I would not get [an implant] right now, because I sometimes
change the [dosage] a little" to adjust to mood, said Stanley,
who has pushed for tougher laws compelling people to take psychiatric
medication.
But he said he could have used an implant as a young man, when "the
only reason I was able to take my pills was because my parents were
there watching me like a 2-year-old."
The first human trials of the device are at least two years away,
Siegel said. But with testing completed on rats and rabbits, Siegel's
laboratory and the three other laboratories affiliated with the project
approached the Food and Drug Administration two weeks ago and requested
a meeting to discuss beginning trials to test the device's safety
in humans, he said. The device will not be on the market for at least
five years.
Ethical concerns about the device -- and psychiatry's long history
of adopting treatments that are later seen as civil-rights violations
-- prompted scientists to gather partisans on both sides of the argument
for yesterday's discussion.
"This is very, very early to begin this conversation,"
said Paul Root Wolpe, a professor of psychiatry and senior fellow
at the University of Pennsylvania's Center for Bioethics. "Very
often, when there is this kind of conversation, it's right before
a pharma company is about to introduce the product."
At the heart of yesterday's debate were the antipsychotic medications
themselves, which have become the primary treatment for serious mental
illness over the last 50 years.
The newer generation of antipsychotics were greeted as miracle drugs
when they were introduced about 15 years ago, and their sales have
climbed to become the fourth highest-selling class of drugs in the
nation, according to IMS Health, which tracks industry sales.
But once outside hospital walls, patients frequently stray from the
drug regimens. One study showed that over a two-year period, 80 percent
of people with schizophrenia stopped taking their medication at least
temporarily, Siegel said.
But one clinician interviewed said that if a long-term medication
implant is administered ethically, it could be an enormous boon to
patients struggling to build an independent life.
"I see so many people who so often go off medication because
they lost their prescription, their doctor was on vacation, they ran
out of medication, the pharmacy was closed," said Laurie Goldman,
a clinical psychologist who sees severely mentally ill patients at
the South End Community Health Center. "They ended up homeless.
They ended up burning down houses."
Audience members raised concerns yesterday about possible widespread
use of implants, most pointedly, the danger that they would be used
in the criminal justice system as an alternative to imprisonment.
Others worried that the managed-care industry would promote implants
because they would offer the cost savings of reduced psychiatric visits.
Unrepresented in the gathering of patients' advocates yesterday were
the most seriously ill people, those so disorganized and isolated
that they are unable to manage their medications at all.
Excerpted from: The Boston Globe, 9.26.3003
----------------------
Your Opinion on Schizophrenia Drug Delivery Implant
Note: If you believe - as we do - that this new medication delivery
system would be a valuable addition to the options available to people
with schizophrenia -please send an email message of support to:
Mary Dankert, Email: mdankert@bbl.med.upenn.edu
This drug delivery system may not be developed if people don't let
the University of Pennsylvania know that this is a valuable addition
to the options available for treatment of schizophrenia.
Note: I see this as good news for helping the many people who have
schizophrenia and who - because of the damage to the brain caused
by schizophrenia - find it very difficult to remember to take medications
on a regular basis. This effort is supported by the Stanley Research
Foundation - a leading Non-profit that supports a great deal of schizophrenia
research to improve treatment for people with schizophrenia. - Editor.
For More information on this new drug delivery system - see:
http://stanley.med.upenn.edu/
For more information on the Stanley Foundation Schizophrenia Research
programs, see:
http://www.stanleyresearch.org/programs/stanley_research.asp
State Lawmakers Preview Award-Winning Documentary of Artist's
Struggle With Schizophrenia at NCSL Annual Health Policy Forum
12/10/03 6:02:00 PM
WASHINGTON, Dec. 10 /U.S. Newswire/ -- Artist John Cadigan today
shared his story of his struggle with schizophrenia with more than
400 members of the National Council of State Legislatures, comprised
of state legislators and staff from across the country at
their annual Fall Forum to discuss health policy. In an effort to
challenge existing negative stereotypes about those who struggle with
severe mental illnesses, Cadigan filmed his life for over 10 years.
Cadigan's story came to life at the NCSL's annual Fall Forum through
a preview of excerpts from the artist's documentary, People Say I'm
Crazy. The documentary has been sweeping film festivals throughout
North America, winning major awards such as the Humanitarian Award
at the Vancouver International Film Festival and the Best Documentary
award at the Chicago International Film Festival. The documentary
has recently been purchased by HBO/Cinemax for airing in summer 2004.
For more information about People Say I'm Crazy, log onto http://www.peoplesayimcrazy.org