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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

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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