Few medical conditions are steeped in as many stereotypes as schizophrenia—it’s rare (but eighty-five thousand North Carolinians have it); schizophrenic people are violent (the condition does not always lead to violent behavior); it’s not a real disease (scientific research has shown that it’s a debilitating, often degenerative brain illness that affects nearly three million Americans).

Scientists, though, also know that many people with schizophrenia will develop violent tendencies, including criminal and self-destructive behaviors. Carolina psychiatrist Diana Perkins has seen this up close. She’s seen people with schizophrenia in police handcuffs after violent outbursts. She’s seen a patient’s broken body lying in a hospital bed after voices in his head told him to leap off a wall. But she has also seen patients live healthy and active lives if the disease is caught and treated early. That’s why Perkins created Outreach and Support Intervention Services (OASIS).

“Patients recovering from a first episode have a good chance for a complete recovery,” she says, “unlike patients who are in the chronic stage of illness.”

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OASIS treats patients who have had an episode of schizophrenic behavior—usually delusions or hallucinations—and have sought help in the early stages of schizophrenia. But seeking help, Perkins says, is just the beginning. Patients have to be dedicated to a medication regimen that can have many side effects. That’s not new. Medication for the disease has been around for decades.

“What’s new is helping people around the education of the illness, and what they can do to control the illness instead of letting it control them,” she says.

What’s also new is the knowledge that patients who do not respond to one medication or who experience severe side effects will often find relief in another similar drug, according to a study led by Carolina researcher Scott Stroup. His study also provides information about which drugs doctors should prescribe depending on how patients respond to medication they’ve already tried.

Such research adds a needed layer to schizophrenia treatment, Perkins says, because for decades patients have been stopping their medication regimens to see if symptoms will return, usually with grim results.

“We know that if a person stops medication, the risk of relapse is very high and the illness starts to take its natural, often degenerative course,” Perkins says. “They have to stay on meds long term. We work with patients about why that’s the case.”

Perkins says that people with early-stage schizophrenia often know that their minds are playing tricks on them. “Early on, people can have a lot of insight,” she says. “Patients buy into it. They think, ‘It’s a brain disease. My brain is short-circuiting, and these meds help restore normal function.’”

If patients can be helped to reach these conclusions rather than accepting their own explanations, then they are more likely to stay on medication and get better, Perkins says.

The trouble with drugs

There are many kinds of schizophrenia medication, but all of them work by blocking dopamine receptors in the brain. Dopamine is a pleasure neurotransmitter, so blocking it can result in dulled emotions. “People really hate that,” Perkins says. “Newer meds are much less likely to have that side effect.” The new drugs partially block dopamine receptors, but they have other side effects, such as the need to sleep a lot, daytime drowsiness, and feelings of restlessness. “Weight gain is the worst side effect because of the diabetes risk,” Perkins says. “About a third of the patients treated with some of the newer antipsychotics will gain a lot of weight, sometimes fifty pounds or more.”

Although these side effects can be serious, patients often stop taking medication for other reasons. It’s expensive, and if symptoms completely disappear for a year or two, patients often choose to go without, Perkins says, despite the good chance of symptoms returning. “Maybe not in the first week or first month, but within a year or two, a relapse will likely occur. And unlike the first episode, the patient may not completely recover from a relapse. We still want to be involved even if they choose to stop taking medications, because if a relapse happens, we want to catch it early, maybe prevent hospitalization or minimize consequences.”

Perkins says that there is no evidence that medication cures schizophrenia, even though patients who don’t relapse while on medication often believe that they’ve been cured.

OASIS uses medical evidence to show patients why medication is so important. For a small percentage of people with schizophrenia, Perkins says, the condition will run its course with or without drugs. Sometimes that course leads to chronic schizophrenia, which is when hallucinations, delusions, or other symptoms such as problems with organization set in. Here, medication might not help. Other times, people develop a mild form of the disease that lacks the degenerative element. “But early treatment makes a big difference for probably a third to two-thirds of people with schizophrenia,” Perkins says. “Most people will dramatically recover from a first episode. And for 80 to 90 percent of patients for whom medication works, the symptoms go away completely.”

Despite mounting research that supports drug therapy, Perkins says that true stories are often more effective. Of the many patients she’s been working with for a long time, only one has stayed on meds long term. And that patient is the only one never to relapse.

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“One of the most heartbreaking stories for me is about a patient who had a first episode, and recovered completely on medication. He was working full-time at a prestigious job. He had a good income. He got engaged. And then he didn’t want to have schizophrenia anymore, so he stopped taking medication, and he had a relapse about six months later. He had symptoms for a year before he was hospitalized, and he has not fully recovered from that second episode.”

His girlfriend and job are gone. His life is completely different. “He hears voices all the time—every hour,” Perkins says, “even while on medication.”

Brain circuitry

Why patients stop drug therapy is linked to schizophrenia’s mysterious pathology, which is different from person to person. Carolina psychologist Aysenil Belger is uncovering the science behind the disease.

She uses neuroimaging technology to measure blood flow and blood oxygenation changes linked with particular brain functions in autistic and schizophrenic patients. When you make a decision, speak, or listen, blood flow and oxygen consumption increase in the specific brain regions engaged during these functions.

Belger has found that during attention and decision-making tasks, blood flow and oxygenation to certain parts of the brain are typically a lot less in people with schizophrenia. And tests typically indicate that patients with schizophrenia have trouble with certain decision-making tasks. Her preliminary tests show that the same can be said for at-risk adolescents—those with immediate relatives diagnosed with schizophrenia but who have yet to show signs of the full-blown disorder.

“The disease has already occurred long before the onset of symptoms or before a person sees a psychiatrist,” she says.

Ten to 15 percent of individuals who have a first-degree relative with psychosis will develop schizophrenia. “But we don’t know what triggers the onset of psychosis in these people,” Belger says, “and that’s what we’re interested in studying—the physiological, cognitive, psychological, and clinical changes that are present before the onset of the illness in at-risk individuals.”

If Belger can find the pathological mechanisms underlying abnormal brain development or function, then there’s a better chance to develop localized treatments or even ways of preventing or delaying the onset of schizophrenia. Right now, medication is a blanket solution, but it’s the only solution.

Subtle beginnings

At most, 10 percent of the people who develop schizophrenia feel fine one day and hear voices the next. The vast majority, Perkins says, experience subtle symptoms first, and these will usually develop during late adolescence or early adulthood. High school or college students in the early stages of schizophrenia will get distracted easily and become disorganized. Grades will slip markedly, and students will often become paranoid or disinterested in friends. Antisocial behavior is a hallmark of the disease.

Perkins says that parents often struggle to differentiate between typical adolescent behavioral changes, drug use, and early warning signs of psychosis. Moreover, early symptoms mimic common occurrences. “Most people’s brains make mistakes in perception,” she says. “You’re in the shower and you think you hear the telephone. Did you hear the phone? This happens to everyone. But with people in early stages of schizophrenia, it happens a lot, and in more profound ways.”

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A person who is developing schizophrenia might first experience frequent misperceptions, like thinking they hear someone calling their name. Next they might hear brief hallucinations, for example a voice saying “Don’t do that!” Eventually a conversation between two people might break out in a sufferer’s mind.

A hallucination will seem utterly clear and real. Perkins says that, on average, a person will experience full-blown psychosis for a year before a proper diagnosis is made and treatment initiated. OASIS aims to shorten that time frame.

“The longer people are psychotic, the more developmental ground they lose,” Perkins says. “They drop out of life, and it’s very hard to regain that lost ground, because from adolescence to adulthood, you are learning how to behave emotionally, intellectually, and socially. Some of our patients are treated for a first episode at age twenty, but developmentally, they are fifteen because symptoms began at that age.”

When patients come to OASIS, social worker Brent Moos and program director Sylvia Saade help them figure out what is happening to them. Moos and Saade offer psychotherapy, group therapy, ongoing education, home visits, and support for family members who often struggle with the idea of a mentally ill loved one.

“All the studies show that first-episode patients see really great recovery symptomatically, but some never recover function,” Perkins says. “OASIS spends a lot of time figuring out the individual’s roadblock to functional recovery.”

A second reason to intercept it early is to avoid the trauma and stigma that stem from full-blown chronic schizophrenia. In these cases, patients struggle to rejoin society in a meaningful way. Untreated illness is also associated with increased risk of a person hurting themselves or someone else.

Ultimately, that’s what Perkins wants to avoid.

There are twelve early detection and treatment clinics in the United States, and more than fifty others around the world. OASIS in Chapel Hill receives support from the Duke Endowment, the Kate B. Reynolds Charitable Trust, and Carolina’s psychiatry department. Diana Perkins is professor of psychiatry, and Scott Stroup is associate professor of psychiatry. Aysenil Belger, associate professor of psychiatry and psychology, recently won a Hettleman Prize for Artistic and Scholarly Achievement for brain research.