A major hurdle is identifying those at risk for developing psychosis in the future.
One of the reasons schizophrenia is so disabling is that obvious psychotic symptoms — which are what usually prompt treatment — occur relatively late in the disease process. By then, cognitive function, as measured by various neuropsychological tests, is already lower on average than in healthy individuals.
Neuroimaging studies have revealed that patients in this earlier "prodromal" phase have lost gray matter (neurons and other brain cells) when compared with controls — indicating that some underlying brain damage has occurred. And a preliminary study suggests that patterns of brain activation are already abnormal in those who may be at risk.
Since the mid-1990s, researchers around the world have been evaluating ways to prevent psychosis in patients most at risk for developing schizophrenia. The hope is that early intervention efforts might alter the disease course in a way that would improve outcomes and prevent disability.
A key obstacle is better identifying the young people most at risk for developing psychosis. Many investigators are therefore advocating for targeted interventions based on a more precise estimation of disease stage.
Aiming for Early Detection
Heart disease provides a dramatic example of the benefits of early detection, with blood pressure medication and cholesterol-lowering drugs literally saving the lives of many people who are deemed at risk on the basis of clinical tests. But the earliest warning signs of schizophrenia are more subtle and less specific than those for heart disease. Nonetheless, researchers agree that vulnerability to schizophrenia begins in the womb, and that the disease progresses through five stages.
Premorbid. Subtle cognitive and social difficulties — such as a child who is a slow learner or has trouble playing with others — are the earliest signs of schizophrenia, but also may suggest other developmental problems.
Prodromal. This phase involves an intensification of social difficulties and muted or fleeting psychotic symptoms, such as strange thoughts, odd perceptions, or hearing or seeing something that is not there. In the prodromal stage, an individual understands that these perceptions are not real.
Psychotic. The onset of frank psychosis is often dramatic and sudden. It is characterized by florid hallucinations and delusions, the "positive" symptoms of schizophrenia. Moreover, the individual now believes his or her perceptions to be real ("the television is talking to me"). At this phase the goal is to begin antipsychotic treatment as soon as possible.
Transitional. In this phase, the patient may recover from the first psychotic episode, but is prone to relapse. This is also a time when other disorders, such as anxiety or depression, may develop in conjunction with schizophrenia.
Chronic. In this final phase, the patient becomes more stable, but is likely to suffer persistent cognitive and social deficits — the "negative" symptoms that contribute to disability.
Schizophrenia prevention studies attempt to intervene at the prodromal stage. But only some people who develop prodromal symptoms later experience a psychotic episode — a transition known as "conversion." The results of early prevention studies have reported conversion rates ranging widely from 9% to 76% of participants, with a mean of about 30%. Researchers have therefore been trying to find ways to improve detection of those likely to convert to psychosis — which would reduce the number of people being treated for a problem they would never develop.