Hope on the Horizon
Researchers test a new approach to treating schizophrenia
A study at the University of Michigan examines the idea that schizophrenia may be linked to disturbances in the body’s ability to regulate acetylcholine, rather than dopamine alone
   



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New pieces of the puzzle

Schizophrenia, the second most common mental illness after depression, has puzzled researchers for a century, but new findings may change treatments for this brain disorder.

Clinicians used to believe that schizophrenia stemmed from poor parenting, but now that researchers can pinpoint major differences in the brains of schizophrenics, few caregivers talk about that. Still, the medications that exist are inadequate and misunderstandings about the disease abound.

  • Oxygen deprivation at birth may cause the onset of schizophrenia before age 22 for women and 19 for men, said Tyrone D. Cannon, who led a team of UCLA researchers. The findings are in the May issue of American Journal of Psychiatry.

Eighty randomly selected birth records of patients with schizophrenia in Finland in 1955 were compared to the records for 61 siblings without the disease and 56 nonrelated adults matched for age, gender and social class. The study showed that prenatal infection, fetal growth retardation and social class were not related to schizophrenia, but obstetrical complications that deprived the baby of oxygen around the time of birth did appear to double the chances of developing the disease.

But the disease apparently takes hold only if a child has a genetic predisposition for it, researchers said. Oxygen deprivation makes it more likely that the disease will progress.

  • A gene on Chromosome 1 may be responsible for making some people vulnerable to schizophrenia, researchers at Rutgers University and the University of Toronto found. Several other genes on different chromosomes may be involved with the onset of the disorder, too. The results of the study are in the April 28 issue of Science.

The Center for Inherited Disease Research, a laboratory supported by the National Institute of Mental Health and the National Institutes of Health, helped analyze the findings.

Anne Bassett, associate professor of psychiatry at the University of Toronto, led the 12-year study of 22 families with a high incidence of schizophrenia. "The finding is very strong," said Linda Brzustowicz of Rutgers. "This is approximately 100 times stronger evidence for the existence of a schizophrenia gene than reported in previous studies."

~ Mary Elizabeth Hopkins

By Mary Elizabeth Hopkins
June 8, 2000
Illustration: Artville

A glimmer of hope shines in the eyes of researchers trying a new treatment for schizophrenia – in most cases a baffling, chronic and incurable brain disease that separates its sufferers from reality.

The news might not affect schizophrenics or caregivers for the next few years because even larger studies will be necessary. But caregivers are desperate, said Rajiv Tandon, MD, professor of psychiatry and director of the University of Michigan Health System Schizophrenia Program, so participating in the studies may be worth any risks and concerns.

Tandon is leading a study at the university that examines the idea that schizophrenia may be linked to disturbances in the body’s ability to regulate acetylcholine, rather than dopamine alone. Two other studies in the United States and one in Germany focus on a similar hypothesis.

Although conservative among psychiatrists who treat schizophrenia, Tandon is optimistic that cholinergic medications may point to a new way to treat this disease.

Acetylcholine – which is difficult to study because it affects several systems in the body, including the circulatory and digestive system – has intrigued researchers for a century as a possible link to schizophrenia. But only since the emergence of two tolerable cholinergic drugs for Alzheimer’s patients have researchers been able to try one of them, Aricept (donepezil hydrochloride), on schizophrenics who also take anti-psychotic medications.

"It is quite interesting, [Tandon’s] approach," said Constance Lieber, president of the board of directors of the National Alliance for Research on Schizophrenia and Depression, which partially funded the study at Michigan. "I think we need this, because I don’t think there will be one course of treatment for schizophrenia." The National Institutes of Health and Scottish Rite also funded the study.

It is well-documented that treating schizophrenia with medication within the first three to five years after diagnosis can keep the disease from progressing, Tandon said. If more caregivers and patients knew about it, he said, it could prevent the devastating and irreversible brain damage that schizophrenia usually causes.

"The sooner one is diagnosed, the better," said Nancy Mann, RN, a Clinical 2 nurse at the University of Michigan, who has worked with Tandon. "There’s absolutely nothing good about the diagnosis for patients, but the study could have real promise for schizophrenics."

In the past, clinicians tended to either undermedicate schizophrenics because of a nihilistic attitude toward the disease, Tandon said, or to prescribe as many as six medications to control the symptoms.

Although four newer medications – clozapine, risperidone, olanzapine and quetiapine – have improved symptoms for schizophrenics in the United States during the past decade, they still focus on dopamine regulation in the brain.

While dopamine is clearly part of the problem, Tandon said that anti-psychotic medications are ineffective 30 percent to 40 percent of the time. Even when they are effective, they leave significant deficits and can cause severe side effects, such as tardive dyskinesia and weight gain.

Older and newer medications for schizophrenia, if they work at all, most often address symptoms such as delusions and hallucinations. The existing medications hardly touch the second and third set of symptoms, Tandon said. Those, unfortunately, are the ones caregivers most often grapple with, he said.

Many schizophrenics in the United States live in institutions and are dependent on others. Fewer than 10 percent are employed. Symptoms such as lack of motivation and poor hygiene result in a poor level of functioning, which leads to a marginal life at best.

Cognitive deterioration, possibly the most devastating symptom, means that many schizophrenics, no matter what their native intelligence level before onset, deteriorate to about an 80 to 84 IQ, Tandon said.

Mann’s work revolves around teaching schizophrenics to function as well as they can.

"A lot of things go into the total package," she said. "The meds are of primary importance, but everyone has been looking at life skills, too."

A grant from the Flinn Foundation allows Mann to visit schizophrenics at clubhouses, drop-in centers and Rose Hill Center, a structured farm where she teaches patients how to problem-solve, set goals and live with others.

"The ones that are having a hard time participating in the life skills training are the ones on the older medications," Mann said.

Her article in the Archives of Psychiatric Nursing ("Psychosocial Rehabilitation in Schizophrenia: Beginnings in Acute Hospitalization" Vol. 7, No. 3, June 1993) describes her work with inpatients.

"As a strategy, I’m interested in all aspects of treatment," Tandon said. "It’s a hypothesis, but the treatment we’re trying certainly has benefits for the delusions and hallucinations, and it probably alleviates tardive dyskinesia and cognitive deterioration. It may also have a secondary effect on lack of motivation and poor hygiene.

"Despite all our significant advances, in all honesty, we still don’t precisely understand schizophrenia, and it’s not for lack of looking. But we are likely to achieve major improvements in our treatment approaches over the next decade."