Prediction of Psychosis in At-Risk Youth: a New Study

  • A longitudinal study with a 2½-year follow-up of 291 at-risk individuals was conducted to determine the risk of conversion to psychosis. (Prediction of Psychosis in Youth at High Clinical Risk, a Multisite Longitudinal Study in North America.) The researchers posited that prevention models now common to medicine could possibly be applied to psychotic disorders.


    Efforts to date focused on developing and validating criteria for determining individuals at risk for imminent onset of psychosis. Such studies followed clinical high-risk or prodromal patients over time. Their aims were to facilitate application of interventions before the schizophrenia took hold, thus reducing or preventing a more chronic form.

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    The newest longitudinal study, the largest of its kind, had as its main outcome measure the time to conversion to a fully psychotic form of mental illness. The risk of conversion to psychosis was 35 percent. Five features assessed at the beginning of the study contributed uniquely to the prediction of psychosis: a genetic risk for schizophrenia with recent deterioration in functioning, higher levels of unusual thought content, higher levels of suspicion/paranoia, greater social impairment, and a history of substance abuse.


    However, when prediction algorithms combined three of these variables (genetic risk for schizophrenia with recent functional decline, higher levels of unusual beliefs or suspiciousness, and greater social impairment) it resulted in dramatic increases in positive predictive power: 74 percent to 81 percent.


    These results applied to a treatment-seeking population that was recruited and screened for psychosis risk indicators. The results aren't expected to be useful in general population screening.


    The researchers suggest, "Deficits in social functioning are among the most robust behavioral correlates of genetic risk for schizophrenia and are present in many at-risk individuals from childhood."


    From what I've read, it's not a matter of whether someone will develop schizophrenia, but when to medicate those at risk. According to the researchers, "The present criteria for a prodromal state reflect emerging clinical symptoms and signs that are thought to be on a continuum with fully psychotic states." Thus: "The prediction results apply to a population that is already to some extent ill, rather than to a completely clinically unaffected population." As a result, "It is more appropriate to view prediction in this context in relation to risk of progression and increase in severity of illness than to the risk of illness per se."


    Yet again, the case is made, via empirical knowledge, that early intervention is pivotal in halting the devastating symptoms of schizophrenia. In 2 ½ years, things could change swiftly. This window of opportunity is too long. If someone waits two years to get treatment, there's no guarantee he or she will do well. The goal is to prevent psychotic symptoms and functional disability. The sooner a person gets treatment, the better. I know of no one who had optimal results when he went without treatment for two years before going on the medication. To play the "wait and see" game is risky. It's like playing Russian roulette. Some people could recover even though they haven't been treated immediately, but most people don't, and there's no way to predict who will.


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    The question of treating or not treating people at risk with drugs has been debated for a number of years now. The latest study gives us a better indicator of whether or not to use antipsychotics at the onset of symptoms, or even before the symptoms start. Ideally, the results will be replicated in future studies.


    Also, in a study such as this, it will be interesting to see how the prognosis turned out for those individuals given medication at lightning speed. Would they recover more fully than someone who went without pills? What if they didn't stay on their meds? Does stigma come into play even with early treatment? These are interesting questions to ponder.



    Archives of General Psychiatry/ Vol. 65 (No. 1), Jan 2008

    Tyrone D. Cannon, PhD; Kristin Cadenhead, MD; Barbara Cornblatt, PhD; Scott W. Woods, MD; Jean Addington, PhD; Elaine Walker, PhD; Larry J. Seidman, PhD; Diana Perkins, MD; Ming Tsuang, MD; Thomas McGlashan, MD; Robert Heinssen, PhD

Published On: January 10, 2008