Schizophrenia Scientists Get Closer to Golden Ring

Lynn DeLisi, M.D., a professor of psychiatry at New York University, is engaged in a whirlwind of activity in her office. She is trying to straighten out an Internet server problem, pour a cup of coffee, and welcome a visitor all at once.

Nonetheless, she has not lost sight of her loftier goal—pinpointing when the human brain at genetic risk for schizophrenia actually starts succumbing to the illness. “We currently don't know,” she admits.

She began her study a year ago. A large number of teens and young adults at high genetic risk for schizophrenia are already enrolled; more are to come. She and her colleagues plan to follow their subjects from two to five years to see how their brains change in structure and function and whether certain brain changes correspond with developing schizophrenia.

DeLisi is one of a growing cadre of scientists throughout the world who are attempting not only to flag the earliest signs of schizophrenia, but also to take preemptive strikes against the illness at this stage.

Valuable Insights Obtained

Although undisputedly challenging, such research is already leading to some valuable insights.

For example, Eve Johnstone, M.D., a professor of psychiatry at the University of Edinburgh in Scotland, and her colleagues followed 66 young adults at high genetic risk of schizophrenia for two years. They found that those who developed the illness showed a marked reduction in the size of the right temporal lobe of the brain, whereas the others did not. This finding was reported in the August 2002 British Journal of Psychiatry. Since then, Johnstone and her team have discovered that young adults who develop schizophrenia show a different pattern of gray matter decline in the left temporal lobe and the right cerebellum of the brain than do young people who do not develop the illness. This finding is in press with NeuroImage. Still other glimpses into how the brain on the brink of schizophrenia changes once the illness sets in have been submitted to Brain and Biological Psychiatry, Johnstone told Psychiatric News.

Practical Benefits Accrue

Such research is also leading to some practical benefits.

For instance, Zucker Hillside Hospital in Lake Success, N.Y., has a program in which youngsters showing early signs of schizophrenia are not only studied but helped. Since the hospital's Recognition and Prevention Program opened in 1998, some 150 adolescents have gone through it, and about 80 percent of them have been stabilized and shown improvement in being able to stay out of the hospital, go to school, and keep their friends.

In other words, “the research combined with treatment.. .is definitely helping in that these are symptomatic youngsters in need of help,” Barbara Cornblatt, Ph.D., said in an interview. Cornblatt is a professor of psychiatry at Albert Einstein College of Medicine and director of the program.

What's more, she pointed out, “We have identified a population of adolescents who were falling through the cracks before, and they are now receiving excellent care from both our program and a number of others around the country and around the world.”

Greater Payoff Possible

Another payoff from such research, however, could be even more impressive—delaying, or even preventing, schizophrenia. Indeed, there are already some very preliminary but encouraging findings in this domain.

In 2002, for example, Patrick McGorry, M.D., Ph.D., executive director of the ORYGEN Research Center at the University of Melbourne in Australia, and his colleagues reported that an antipsychotic medication combined with cognitive-behavioral therapy appeared to delay the development of schizophrenia in subjects at high risk (Psychiatric News, November 15, 2002).

Since then, McGorry said, “We have followed up most of them, [and there has been] some, but not much further, progression [of their schizophrenia].”

Also in 2002, Thomas McGlashan, M.D., a professor of psychiatry at Yale University, and co-workers reported that giving an antipsychotic medication alone—that is, without psychotherapy— looked promising as a way of delaying schizophrenia (Psychiatric News, June 21, 2002). “We are analyzing the data and plan to submit the study to the American Journal of Psychiatry for review,” McGlashan told Psychiatric News.

The amino acid glycine is known to be a modulator of a glutamate receptor that in turn is known to be abnormal in schizophrenia patients. So Scott Woods, M.D., a professor of psychiatry at Yale University, and co-workers conducted a small, open-label study to see whether glycine might help youngsters in the earliest phases of the illness. They studied 10 subjects who received glycine for an eight-week period.

“Overall they did quite well,” Woods said in an interview.“ The amount of improvement was very substantial and very promising. We are just now finishing the design of a placebo-controlled study” to explore glycine's potential further. They will begin enrolling subjects this summer.

As part of their effort to keep adolescents with early signs of schizophrenia out of the hospital, in school, and functioning as well as possible, Cornblatt and her colleagues gave some of them antidepressants, then followed their outcome over the next two or three years.

The antidepressants seemed to help these adolescents as far as depression and anxiety—especially social anxiety—were concerned, she said. So she and her team are now conducting a randomized, double-blind study to see whether antidepressants can truly counter such symptoms in young persons.

But will it be possible to delay or prevent schizophrenia in such youngsters within the next five to 10 years?

“It would be wonderful if this could actually be done,” Johnstone admitted, “but I am not aware of any credible evidence that it is likely that, in the present stage of knowledge, schizophrenia will be preventable in the foreseeable future.”

“I am absolutely optimistic about delaying the onset of it even if we can't stop it,” said Delores Malaspina, M.D., a professor of clinical psychiatry at Columbia University and an authority on schizophrenia pathophysiology.

Woods expressed optimism about both schizophrenia delay and prevention. In fact, when asked to predict whether delaying and preventing schizophrenia might become feasible within the next decade, he replied, “I do think there is a chance.” ▪