Early Recognition and Prevention During the Psychotic Prodrome. After more than five decades of increasingly refined psychopharmacologic developments, schizophrenia has remained one of the most severe and disabling disorders in medicine. Since interventions after a first schizophrenia episode have not been able to alter the generally chronic and relapsing disease course (Robinson et al. 2004), early intervention and prevention of schizophrenia are a vital goal. Initial, retrospective studies that demonstrated presence of a symptomatic prepsychotic illness phase of clinically relevant severity and duration (Hafner et al. 1999) provided the practical basis for early identification efforts. Several lines of evidence further supported the potential utility of early interventions for the schizophrenia prodrome. These include an increasing appreciation that schizophrenia is a neurodevelopmental disorder characterized by early developmental delays and problems, and that is further associated with a significant functional decline and brain morphological changes (Correll and Kane 2004;Sawa and Snyder, 2002;Woods 1998). Moreover, the duration of untreated psychosis (Marshall et al. 2005), and number of relapses have been associated with decreased grey matter and worse functional outcomes, even after controlling for potentially relevant confounders (Perkins et al. 2005). Importantly, brain morphological changes have also been demonstrated during the transition from prodromal psychosis to full blown psychosis (Pantelis et al. 2003), suggesting that early intervention may be a potential vehicle to effectively interrupt biological processes involved in the development of psychosis and its adverse functional consequences. Prodromal schizophrenia research conducted over the past ten years at our Center and others has further consolidated the evidence that early identification and intervention studies during the schizophrenia prodrome are possible. Early recognition programs have identified high risk samples with conversion rates to psychosis between 10 and 40% over one to two years (Yung et al. 2008). In the largest study to date by the North American Prodromal Longitudinal Study (NAPLS) group of which Dr. Cornblatt at our Center is one of the PIs, a conversion rate of 35.3% over 2.5 years was reported (Cannon et al. 2008). These conversion rates to psychosis are 10-40 times the prevalence rate observed in the general population and far greater than the expected incidence rate during such a brief time period (Eaton 1999).

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