Progress in the Treatment of Schizophrenia

You're a senior in high school, sitting in math class, when suddenly a voice from the loudspeaker tells you the CIA has killed your parents and replaced them with impostors. Days later you notice strangers watching you. In fact, they are listening to your thoughts. No one can convince you that your ideas are irrational and, because you don't feel ill, you refuse to see a doctor. Instead, you tell a friend you will foil the conspiracy by committing suicide. Hours later, the police arrive to take you to a hospital.

This is one of the common ways schizophrenia announces itself. Before World War II, if you developed this illness, you would most likely spend the rest of your life in a psychiatric hospital. Dramatic treatments were attempted: surgical cutting of connections to the front of the brain, infusing insulin to induce a coma, or plunging patients into a tank of cold water. But these procedures did little to alleviate suffering. Finally, in the 1950s, medications were found that provided relief from hallucinations and delusions. But patients often put up with troubling side effects such as tremors, sedation, weight gain and diabetes. And relapses still occurred.

But now there is hope that we may be at the threshold of the next generation of schizophrenia treatments. Using brain scanning in live patients and laboratory analysis of brain tissue collected after death, neuroscientists have identified subtle abnormalities of brain structure in patients with schizophrenia. For example, the brain seems to shrink in size during the early stages of the illness. Changes have also been found in the chemicals and receptors that govern how nerve cells communicate with one another. It's not enough, however, to identify changes in brain structure. To help the brain work right, scientists must first understand where brain function goes wrong in schizophrenia. Brain imaging can now demonstrate abnormal patterns when patients are asked to perform perception and memory tests. This may be the source of psychotic experiences.

Schizophrenia almost certainly has more than one cause. For any individual, several factors probably work together to produce the illness. Genes have been identified that increase the risk of the disease. Vulnerable people may stay healthy if they avoid exposure to triggers such as a nutritional deficiency, an infection, a toxin or other stress during critical periods of brain development. Prevention of triggers could lower risk.

Sorting out the genetic puzzle will require the study of tens of thousands of patients, since the effects of single genes are small. Scientists are rapidly identifying new risk genes and working to clarify their biological role. They are also discovering new ways that risk genes get transmitted. Older fathers, it turns out, may be more likely to pass along schizophrenia risk genes than younger fathers. And, surprisingly, risk genes may not always be inherited. In the past year, researchers discovered that spontaneous mutations deleting entire genes may play a role.

Some genes regulate the chemical messengers that enable healthy cell-to-cell communication. For the most part, anti-psychotics used today work by blocking one of those messengers, dopamine. But another chemical, glutamate, may be just as important. It is integral to brain processes involving perception, memory and learning. The street drug phencyclidine (PCP), which blocks receptors for the glutamate molecule, produces schizophrenia's symptoms: psychosis, apathy, withdrawal and problems with memory and concentration. One drug now under development targets glutamate receptors and has produced impressive symptom improvement in early experiments. If the results hold up, it will be the first schizophrenia drug not directed at dopamine.

Neurotransmitters are only part of the story. Scientists have discovered genes that guide nerve cells during brain development to migrate to the right place and make the right connections to other nerve cells. Techniques for fixing physiological misfirings caused by mutated genes are still in the realm of science fiction.

Specialized nonpharmacological techniques will also have to be part of standard treatment for this disease. The goal is to start that work as early as possible, in the hope that progression can be halted. Teams of mental-health professionals can help patients find and keep jobs, prevent relapse and allow patients to live independently, while new approaches to psychotherapy help patients cope when drugs fail.

If you are that unsuspecting high-school student with schizophrenia, you, your family and your clinicians may carry frustrating burdens that go beyond the illness. Of all the ways in which the brain can become damaged, schizophrenia remains the least understood and the most frightening. Society sympathizes with stroke victims or Alzheimer's disease sufferers, but it stigmatizes schizophrenia. The illness is exhausting, resources are scarce and humane treatment may be hard to get. Yet research is already showing us the kind of treatment and support that can help. And, in the future, early identification and treatment could prevent the illness entirely.