In another study, published in 2002, the University of Melbourne’s McGorry reported that a combination of medication plus CBT was more effective at preventing schizophrenia than psychotherapy alone, though several of the patients in the study later became psychotic. McGorry would like to see further clinical research, and he’s currently conducting a randomized clinical trial that compares CBT with an antipsychotic drug called risperidone.

McFarlane, meanwhile, points out that although PIER’s patients aren’t yet psychotic, most come to the clinic in severe psychiatric distress, and when PIER provides comprehensive treatment, their symptoms generally improve. He says that among the patients, it is mostly those who have refused or stopped treatment who have gone on to suffer psychosis.

McFarlane says PIER’s not-yet-published data indicates that the program’s combination of medication and psychosocial support cuts patients’ risk of psychosis roughly in half. And PIER, which now uses a drug called aripiprazole that may pose fewer metabolic risks than other medications, is not testing how much that success depends on the drugs. Most of the team’s effort is devoted to reducing stress and improving the young person’s academic or work performance, saving medication only for those with more severe symptoms. “The risks of not using any medication are too high,” says McFarlane. “We might be consigning half the people in the trial to mental illness.”

In the future, physicians may be able to identify physical signs, or biomarkers, indicating whether a particular patient is likely to develop schizophrenia. Some research is looking at brain-imaging data and gene-based biomarkers, says Tyrone Cannon, a professor of psychology and psychiatry at UCLA. In tracking brain changes leading from prepsychotic stages to schizophrenia, Cannon and his colleagues are testing the theory that prodromal symptoms appear as the adolescent brain “prunes” synapses, a process known as plasticity.

Just as removing a tree’s weaker branches allows its other branches to flourish, synaptic pruning strengthens needed connections while ridding the brain of those it no longer requires. But Cannon thinks this process goes haywire in the prodromal brain—that instead of eliminating synapses selectively, the brain hacks away at them indiscriminately or overaggressively. Better knowledge of that process and its genetic underpinnings may one day yield a range of diagnostic enhancements, he says. By combining biomarkers with the SIPS evaluation and other tools, clinicians might be able to reduce the number of patients mistakenly diagnosed as prodromal. Better knowledge of schizophrenia’s biological roots might also lead to improved drugs for treating it, such as compounds that protect brain synapses and plasticity.

“There have been phenomenal advances in understanding schizophrenia in the past decade, but we’re no closer to a cure than we were 30 years ago,” says the NIMH’s Heinssen. “So it’s exciting that if you catch schizophrenia during the prodromal phase, you might be able to keep it from progressing.”

  Dossier

1. “Prediction of Psychosis in Youth at High Clinical Risk,” by Tyrone D. Cannon et al., Archives of General Psychiatry, January 2008. Involving 291 patients from research centers countrywide, this study was the largest to date to investigate the degree to which prodromal symptoms can predict schizophrenia—perhaps as often as 80% of the time.

2. “Prodromal Assessment With the Structured Interview for Prodromal Syndromes and the Scale of Prodromal Symptoms: Predictive Validity, Interrater Reliability, and Training to Reliability,” by Tandy J. Miller et al., Schizophrenia Bulletin, Vol. 29, No. 4, 2003. Describes the origins of the key diagnostic tool for prodromal symptoms.

3. “Family Expressed Emotion Prior to Onset of Psychosis,” by W.R. McFarlane and W.L. Cook, Family Processes, June 2007. This study concludes that the heightened “expressed emotion” —criticism and anger—that families experience during a member’s prodromal phase is a reaction to, not a cause of, the member’s symptoms.

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