A young man we’ll call John had been hospitalized multiple times for acute anxiety and
      depression when he began hearing voices and seeing violent images. The 19-year-old rarely left his parents’ home in a Portland, Me., suburb, and he had threatened suicide. Yet, desperate as his situation seemed, it was hardly unique. Each year thousands of adolescents and young adults are struck by similar symptoms that frequently, perhaps one time in three, prove to be the precursors to full-blown schizophrenia, a grim diagnosis of delusions and paranoia.

More often, though, schizophrenia doesn’t develop, so doctors have tended to proceed cautiously as they try to determine exactly what is troubling these young people. But William McFarlane, a psychiatrist at Maine Medical Center in Portland and director of a mental health program called Portland Identification and Early Referral (PieR), doesn’t wait. In John’s case, McFarlane and his staff moved to block John’s anticipated psychotic illness with a mix of medication and family counseling that helps patients cope with stressful situations at school and work. Two years later, John is living on his own for the first time, holding down a job at a Goodwill store and hoping someday to go to college. “They helped me control my emotions and deal with the images in my head,” he says. “I can go about my life now in a way that I couldn’t before.”

McFarlane thinks that, at least some of the time, schizophrenia can be headed off—and that measured against the undoubted perils of the disease, early action is justified. A condition that may account for as many as 25% of the suicides among young people in the United States, schizophrenia is notoriously difficult to treat. As patients begin to lose touch with reality, they tend to withdraw, putting themselves far beyond the reach of those who might help them. But studies show that one to two years typically pass between the onset of symptoms and the first psychotic breakdown, and McFarlane’s approach is to act decisively during this precursory, or prodromal, phase. Other scientists also advocate aggressive treatment during the prodrome, though

McFarlane is more willing than most to take the controversial step of prescribing antipsychotic drugs to patients with severe symptoms who may or may not ultimately develop schizophrenia.
The potential benefit of keeping schizophrenia at bay, perhaps permanently, is huge, and McFarlane’s methods are now getting a much broader test. His research program has expanded from Portland to small cities in California, Michigan, New York and Oregon, and depending on the study’s conclusions, McFarlane’s methods could one day contribute to routine clinical practice. Meanwhile, other research is rushing ahead in the United States and elsewhere.

Harry Stack Sullivan, the American psychiatrist best known for his theories of how interpersonal relationships fuel mental illness, wrote in a 1927 letter to a colleague that “incipient” cases of schizophrenia “might be arrested before the efficient contact with reality is completely suspended.” Yet during Sullivan’s era, and for decades afterward, the mainstream view was that schizophrenia “doomed patients from the womb,” says Jeffrey Lieberman, chair of psychiatry at Columbia University’s College of Physicians and Surgeons.

It wasn’t until the 1980s that research began to suggest otherwise. It appeared that if patients were treated with drugs and talk therapy soon after their first psychotic break—the point at which they had lost the ability to recognize that their hallucinations and delusions weren’t real—there was a decent chance they’d recover. Those who got quick attention had symptoms that were less frequent and less intense, and there was less evidence of brain damage. “Until then, there wasn’t any real rush to treat,” says Lieberman. “But we recognized that the faster the patients were treated, the better.” Eventually that focus shifted to an even earlier stage, when outright prevention might be possible.

The consensus today is that prodromal symptoms typically emerge during the teen and early adult years. Preliminary imaging studies show that brain changes associated with schizophrenia follow a steady progression and likely involve an increasing loss of synapses between individual nerve cells, particularly in the frontal lobes, where language, memory, socialization and other behaviors are coordinated. Additional preliminary imaging studies also show steady declines in gray matter, spreading out from the frontal lobes as patients shift from prodromal states toward more definitive disease.

When the number of synapses dwindles, prodromal patients begin losing powers of judgment and reason and may feel overwhelmed as they’re deluged with unprocessed sensory stimulation. Hallucinations and delusions ensue—slowly at first, but gaining in intensity until a psychotic break occurs. Like others at this stage, John experienced moments when he would hear or see things that weren’t there. But unlike truly psychotic patients, who think their hallucinations are real, he could still be convinced that he was, in fact, hallucinating. That capacity to distinguish hallucinations from reality is what sets the prodrome apart from psychotic disease.