The first time Rose had a vision, she “took it as something spiritual.” She heard animal noises and furniture moving. She says, “I felt this evil presence on my chest. I saw writing on the wall. It looked like another language. I was scared.”

That vision lasted only about three minutes. Afterward, she put on some soothing music and tried to calm down.

She had another short vision about a year later. But the next year, when she was 33, Rose had a longer episode of delusions and hallucinations-what psychiatrists call psychosis, in which a person loses contact with reality.

This time, she says, “I was living it out. I was identifying myself with people in the Bible. I went to a park and kept vigil there, as if I were at the garden of Gethsemane.” She recited the Psalms out loud, sang religious songs. “I saw spirits,” she says. “They looked almost like ghosts-they were transparent.

Then I became afraid. I thought I had missed the rapture. I thought that I needed to stay there, at the park, but that if I did, I might die. But then, something inside me said, `Just go home.’” On her way home, she saw auras around the houses she passed. Each house was surrounded by a different color.

This episode lasted about three days. Then a concerned neighbor took her to the hospital. “He had kids,” Rose says, “and I trusted him.”

Doctors diagnosed Rose with schizophrenia. The disorder affects two million American adults, making it twice as common as Alzheimer’s disease and five times as common as multiple sclerosis. Symptoms and their severity vary, but can include auditory and visual hallucinations, delusions, disordered thinking, lack of motivation, and an apparent inability to express emotion or acknowledge it in others.

Shortly after she began taking antipsychotic medication, Rose’s delusions faded. But she became clinically depressed. “If it wasn’t for my parents’ help, I couldn’t have made it,” she says. She’s returned to the hospital for schizophrenia and depression several times in the past five years, but only for brief stays.

Like many sufferers of schizophrenia, Rose has had to struggle at times to figure out what is real. Researchers, as well, are haunted by schizophrenia. They know that it’s a physiological disorder of the brain, but the exact cause is still a mystery.

The brain is so complicated that we have no real understanding of how it works,” says John Gilmore, associate professor of psychiatry. “We have ideas about systems and structures, but there are tens of thousands of molecules in the brain that we have no idea what they are, much less what they do.”

When you start out,” Gilmore says, “you think, `I’m gonna figure this out.’ Then you realize, `No, probably not in my lifetime.’ You get to a point where you have to come to terms with that and feel good that you’re contributing a little piece to this puzzle.”

It is known that part of the problem is caused by an imbalance of neurotransmitters, which are chemicals that carry impulses between nerve cells. Psychotic reactions can occur after taking amphetamine or cocaine, drugs that increase the amount of the neurotransmitter dopamine circulating in the brain. And most antipsychotic drugs work by blocking dopamine receptors. But these drugs don’t fix the underlying problem-they only reduce symptoms. So dopamine is probably only part of the answer. Other neurotransmitters such as serotonin and glutamate are thought to be involved too.

It’s also known that complications before birth increase the risk of developing schizophrenia. Research has shown that when a pregnant woman has a nutritional deficiency, her child has a higher risk of developing schizophrenia, Gilmore says. And exposure to flu during pregnancy can also increase the risk.

Gilmore is testing the possibility that proteins involved in the immune response might explain the connection between prenatal infections and schizophrenia. When an infection strikes, the body produces higher levels of cytokines, proteins that help transmit signals between cells. But these proteins can also affect development of the brain’s neurons. Gilmore’s lab grows neurons from rats in culture, then exposes them to cytokines. He’s found that high levels of certain cytokines decrease the survival of neurons that regulate dopamine.

Our hypothesis is that these cytokines find their way to the fetal brain and very subtly alter the developing neurons so that they may die before they’re supposed to, or they may not develop the correct synapses,” Gilmore says.

Though sufferers of schizophrenia share similar symptoms, their illness may have different causes. Schizophrenia is not a well-defined disease, but a disorder-a group of symptoms, says Diana Perkins, assistant professor of psychiatry. Some researchers prefer to use the term “the schizophrenias” rather than “schizophrenia,” according to the Harvard Mental Health Letter.

The course of schizophrenia can be different for each person. Most patients recover from their first episode. But after five years, more than 70 percent of them will have another bout with the illness, says Fred Jarskog, assistant professor of psychiatry. Some have only occasional relapses, while others continue to be chronically ill. “It’s a very heterogeneous illness,” Jarskog says. “That’s one of the difficulties of dealing with schizophrenia.”

Heredity does play some role. A child of two parents with schizophrenia has about a 40 percent chance of developing it. But genes aren’t the only factor. Among identical twins of schizo-phrenics, the disorder occurs at a rate of only 30 to 50 percent.

The risk may also depend partly on environment, says Jeffrey Lieberman, professor and vice chair of research in psychiatry. He compares schizophrenia to diabetes. Just as someone genetically predisposed to diabetes may develop it earlier and with a higher degree of certainty if they eat poorly and don’t exercise, someone with a predisposition to schizophrenia can end up with a more severe form of the illness if they are exposed to more stresses that may set off the disorder, such as recreational drugs, emotional upheaval, or life changes, Lieberman says.

In most cases, schizophrenia first appears without warning when sufferers are in early adulthood or late adolescence, the time when many people leave home, begin college or a job, get married, or experiment with drugs. “Life becomes a lot more complicated,” Lieberman says. “If your brain has some potential for malfunction, it will probably show up at this time.”

Also, late adolescence is when the brain fully matures. Throughout childhood, the neurons in the brain are continually forming new, elastic connections. But as the brain matures, connections are refined and unneeded ones destroyed. This “synaptic pruning” may unmask the chemical imbalance or other problem that causes schizophrenia, Lieberman says.

And the brain structure of some people with schizophrenia is slightly different than that of people without the disorder. For instance, magnetic resonance imaging shows that some sufferers have slightly enlarged ventricles, which are fluid-filled cavities in the center of the brain. This can indicate brain atrophy. But it’s unclear whether these abnormalities were there from the beginning and contributed to the disorder, or if they’re the result of damage caused by psychosis.

There’s evidence for both ideas. Lieberman has led a study that found that the earlier schizophrenia is treated, the better the outcome. This suggests that if the psychosis and chemical imbalance are allowed to continue, it damages the brain, he says, which would explain why, with each successive relapse, most patients recover less and less of their former function.

But, differences in brain structure have been seen in people who have just begun their first episode of schizophrenia, suggesting that problems can begin early in life, Gilmore says. “If you look at the post-mortem brains of people that have schizophrenia, there are very subtle abnormalities that are consistent with early brain-development problems.” It may be that different forms of schizophrenia cause changes at different times.

Right now, there is no cure for schizophrenia. The main treatment is antipsychotic medicine. But establishing a rapport with the patient is also important, Jarskog says.

I try to talk with them about practical things, give them basic advice to help improve their day-to-day living,” he says. “If people don’t feel we really care about them, that they’re just being fed these medicines, it usually doesn’t help any illness.”

It’s common for patients to decide to stop taking their medication, partly because of the harsh side effects of many antipsychotics. These include sedation, dry mouth, blurred vision, restlessness, and tardive diskinesia, which is an involuntary movement of muscles that causes writhing, jerking motions. Tardive diskinesia can be irreversible, even when people switch or reduce medications.

We’re trying to convince people that despite these very unpleasant side effects, they should stay on the medicine,” Jarskog says. “It’s a very tough sell.” Carolina’s Department of Psychiatry is leading an international study that will find out if a new drug causes fewer side effects and is more effective than traditional medicines (see “Improving the Outlook”).

Sometimes patients may simply forget appointments, since the disorder affects their thought processes, says Bebe Smith, clinical social worker in Carolina’s Department of Psychiatry. It may be hard for some patients to believe that they’re ill. Or, they may feel that they’re not getting help for the problems that are most troublesome to them. One patient firmly denied that she suffered from mental illness, but she was concerned about problems with anxiety and sleeplessness. She agreed to take antipsychotic medication because it would alleviate those symptoms as well. Smith says, “The doctor and patient have to find some common ground.”

Smith often tries to track down patients who miss appointments, and she encourages the psychiatrists to do the same. But because of demands on the mental health system, some appointments might never get rescheduled. Smith is the only social worker for Carolina’s Schizophrenia Treatment and Evaluation Program (STEP), which treats about 120 outpatients. Numbers like that are common, she says, partly because public support for sufferers of schizophrenia and other mental illnesses is low. There’s still stigma attached to schizophrenia. Most people with the disorder don’t become violent, Smith says, but often those who do are the only ones we hear about. Also common is the false notion that patients are responsible for their symptoms, Smith says, that if they tried hard enough, they could control them.

While the symptoms can’t be ignored, sufferers such as Rose do look for ways to deal with them. She says, “I think my biggest frustration is not appreciating life, not wanting to live. But it’s gotten better. There was one point where I couldn’t laugh. But now I’m able to express a full range of emotions.

Each person finds their own coping mechanism,” Rose says. She hasn’t given up her faith and finds comfort in church. She also works part time and gets support from friends and from her treatment team at the STEP clinic. “The worst thing,” she says, “is to be isolated.”