2000), it is essential to investigate opportunities for prevention before onset or when symptoms are in the prodromal stage (a period of nonpsychotic symptoms that precedes onset). Findings from a number of treatment studies of early detection and intervention indicate that both atypical antipsychotic drugs and psychosocial interventions are good candidates for testing in youth who are at high risk for a psychotic episode (Haas, Garrett, and Sweeney, 1998; Leucht, Pitschel-Walz, et al., 1999; Lieberman, Perkins, et al., 2001; Loebel, Lieberman, et al., 1992; Marshall, Lewis, et al., 2005; McFarlane, 2007; Pilling, Bebbington, et al., 2002a, 2002b).

To be effective, however, these preventive and early intervention strategies need to overcome some important challenges. First, epidemiological and developmental factors make it challenging to conduct universal, selective, or indicated preventive intervention trials aimed at those who have not yet had an episode (Faraone, Brown, et al., 2002; Brown and Faraone, 2004). Second, preventive intervention strategies are limited by incomplete understanding of the genetic, neurological, and environmental factors leading to these disorders. Third, ethical challenges are posed by the testing of interventions that may do harm and the stigma regarding labeling someone as being at high risk for psychosis. None of these challenges appears insurmountable, however. Moreover, the very high costs of these illnesses when they occur and the fact that experiencing the illness itself predisposes to more episodes make effort in this area warranted.

A number of prodromal clinics worldwide identify subjects from the community at high risk for a psychotic episode. These clinics provide training to mental health professionals, school and community professionals, and the public regarding early warning signs and opportunities for referral. Several are testing an active intervention, including early pharmacological intervention, against a control condition. The prodromal phase is characterized by schizoid characteristics or familial risk, brief or attenuated psychotic symptoms, and social deterioration or negative symptoms (McFarlane, 2007). The criteria used by these clinics to distinguish those in the prodromal phase from those who are not at elevated risk or have already had a psychotic episode are not identical across clinics. However, there is compelling evidence that those identified in such prodromal stages have a very elevated risk for experiencing a psychotic episode in the near future (Yung and McGory, 1996a, 1996b; Yung, McGorry, et al., 1996; McGlashan, Addington, et al., 2007).

The published studies of these preventive interventions indicate a substantial reduction in rates of development of frank psychosis and in prodromal and psychotic symptoms, although one study did not show statistical significance. Using a simple meta-analysis, McFarlane (2007) estimated that the mean conversion rate across studies is about 11 percent



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