What Is Schizophrenia? Scientists Call for New Thinking

Eventually, Jasmin recovered from her catatonic state, but only after things got much worse: a diagnosis of psychosis, a brief hospitalization and powerful anti-psychotic drugs that caused a 40-pound weight gain over three months.

Could the worst of it have been avoided had doctors paid closer attention to Jasmin’s earliest symptoms, particularly her sudden problems with schoolwork and her sensitivity to noise and bright lights?

A new generation of schizophrenia researchers believes these struggles may be some of the earliest symptoms of schizophrenia, symptoms of a cognitive decline that may precede, even cause the delusions and hallucinations the disease is famous for.

A Mysterious Disease

Schizophrenia is twice as common as Alzheimer’s disease, but almost nothing is known about how it works in the body. As with most other mental illnesses, there’s no blood test for schizophrenia, no scan that can diagnose it.

Instead, schizophrenia is defined by symptoms patients describe about themselves, particularly a blurring of the boundaries of reality.

A patient may hear strange, often threatening voices that no one else can hear. She may believe she is being spied on through her television, that she is telepathic, or that newspaper articles contain hidden messages directed at her alone.

These strange behaviors – hallucinations and delusions — have defined the disease since it was first formally described in 1950. The word “schizophrenia” means, literally, “split mind”: a division between what the patient believes is real and what most other people would agree is real.

Society’s preoccupation with hallucinations and delusions is easy to understand, says Sophia Vinogradov, a psychiatrist and researcher at the San Francisco VA hospital.

“They’re right there, in your face,” Vinogradov says. “And they’re frightening. They’re frightening for the person who has them and they’re frightening for society.”

She says that’s why anti-psychotic drugs, which were developed in the 1960s, seemed like such a breakthrough. Until then, nothing else had worked to help people with schizophrenia.“Up until that point we had wrapping them in wet towels, locking them in a padded cell,” Vinogradov says. “Frontal lobotomies if the behavior was really out of control. I mean, what did we have? So when antipsychotic medications did evolve, and they did reduce psychotic symptoms, it was like the heavens had opened.”

But the drugs came with powerful side effects. They left some people virtually comatose. Even the modern versions can cause serious weight gain. That’s one reason people with schizophrenia are at least twice as likely to die of cardiovascular disease.

And in recent years, scientists have begun asking whether the voices are better viewed as a symptom of something else, says Vikaas Sohal, a researcher at UCSF.

“If someone came to you with cancer and said, ‘My back is hurting, my gums bleed, I’m tired, I have headaches,'” Sohal says, “okay, there’s all these things, but that’s not what cancer is. Cancer is this group of cells that are dividing uncontrollably.”

In other words, giving antipsychotics to a person with schizophrenia may be like giving painkillers to someone with cancer. It might help, but it’s not getting at the cause.

Cognitive Decline as the First Sign of Disease

Basic cognitive problems may precede hallucinations and delusions by a decade or more.

Elaine Walker, a professor of psychology and neuroscience at Emory University, studied home movies of young children and noticed that children who would later develop schizophrenia seemed to walk differently than the control group. Their gait seemed particularly abnormal on the left side of their bodies.

Other studies point to a decline in IQ that happens over the time the disease develops.

People in the early stages of schizophrenia “seem to have problems focusing attention, planning, trouble with encoding and storing memories,” says Daniel Mathalon, a neuroscientist at UCSF. “Patients sometimes say they used to be able to read books, now they can’t read books. They can’t sustain focus. They used to build models, now they don’t. They used to be able to play the guitar well, now that’s deteriorated.”

Parents hope, he says, that the problems are “just a phase that an adolescent is going through. Sometimes it is, but sometimes it’s the predecessor to a full-blown psychotic illness.”

A Problem of Information Overload

In recent years, scientists have begun to talk about schizophrenia as a disease of “salience,” in which the brain loses the ability to tune out information that isn’t useful or relevant.

“They are walking down the street trying to have a conversation and their brain is being flooded with the sound of the door slamming, the airplane going overhead,” says Vinogradov, of the San Francisco VA hospital. “The brain is starting to process all of that information as if it has meaning, and is something the brain needs to pay attention to and needs to do something about.”

Maybe, the theory goes, that’s what gives rise to hallucinations and delusions. The mind seeks explanations for the extra data coming in.

“If you pay attention to everything,” says UCSF’s Sohal, “you might start paying attention to coincidences, and you might get paranoid. Or you might pay even more attention to your own thoughts and start thinking, ‘These are other peoples thoughts.’”

New Treatments Emerge

When you change how you define a disease, you begin to change how you treat it.

Increasingly people in the early stages of schizophrenia are prescribed fish oil and exercise, to support basic brain functioning. Drug companies are working on new medicines that could do the same.

At the Citywide Mental Health Center in San Francisco’s Tenderloin neighborhood, Vinogradov is leading a study to see whether the brain can be, essentially, re-taught.

A middle-aged man named George, wearing a crisp short-sleeved shirt, sits at a computer. He’s wearing plastic gloves.

“Why the gloves?” I ask him. “Gloves?” he says. “So the cosmic dust doesn’t get on my hands.”

George can see my voice, he tells me. It looks “yellow, with light pinkish color.” He wants to know whether I’ve ever seen voices, or would like to.

“I don’t know,” I tell him. “Is it a good thing?”

“Yes,” he answers. “You can understand life in general better.”

“You feel like you understand things other people don’t?” I ask.

“Of course,” George says. “It makes you superior.”

As we talk, George drags his cursor across the screen, following directions from a cognitive training exercise designed by the San Francisco software company Posit Science.

“Move the boy to the school,” the voice intones. George complies. He supplies his own commentary.

“OK, he’s going to school, see? Cutting, smoking cigarettes in the back.”

Researchers tend to avoid the term “video games.” These exercises are about as much fun as brushing your teeth. The idea here is to train George to tune out distractions and focus on simple instructions.

Another exercise repeats a word, like asking the user to click on the emotion that best describes how the word is said. They’re given four choices: happy, angry, sad and neutral.

For Some People, Not All.

The idea here isn’t to replace anti-psychotic drugs, at least not for everyone. Vinogradov says there are some people whose voices or delusions are so destructive, so violent, that they need to be turned off.

But for another group of people, doctors might be able to focus on a different set of questions, Vinogradov says.

“Is this person able to have the kind of life they want? Are they able to have friends, to have people who they can love, who can love them back? Are they able to keep food and shelter?”

Vinogradov, Mathalon and others point to studies showing that delusions and hallucinations aren’t always the factors that interfere with a person’s ability to lead a fulfilling life.

By focusing on cognitive problems, says Mathalon, “we might have greater impact on outcomes for patients. We might have a greater impact on whether they can successfully work, have relationships, than if we just quell their psychotic symptoms, keep the voices from intruding.”

Silencing the voices with big doses of anti-psychotic drugs may, in some cases, do more harm than good.