Interest in the possibility of preventing the onset of psychosis has grown in recent years. The identification of individuals at risk will be a critical first step in the development of early prevention trials. It is well established that the clinical onset of psychosis is usually preceded by significant behavioral dysfunction, which becomes most pronounced during adolescence. In fact, the vast majority of patients manifest adjustment problems during adolescence; often a 'prodromal' behavioral syndrome similar to SPD. To date, prospective studies of youth with prodromal signs have shown a high rate of Axis I outcomes (30 to 40 percent) within one to three years, lending support to the utility of behavioral risk indicators. In order to improve predictive validity beyond that achieved with behavioral criteria, a multifactorial approach that includes biological risk factors may be needed. Findings from our preliminary research indicate that adolescents with schizotypal personality disorder (SPD) manifest several physical indicators that have been observed in schizophrenia patients, including dysmorphic features, movement abnormalities, and elevated cortisol. Further, SPD adolescents with more pronounced dysmorphic features, movement abnormalities and cortisol elevations are more likely to show symptom exacerbation or Axis I disorder within two to three years. The proposed research represents a replication and extension of this study. The chief goals are to elucidate the predictive validity of putative behavioral and biological indicators of risk for psychotic disorders, and 2) to shed light on neuromaturational processes that might be involved in the emergence of prodromal features. Of particular interest is the particular role of the hypothalamic-pituitary-adrenal (HPA) axis as a moderating neural system that influences the expression of latent vulnerabilities. The study will explore the direct and interactive effects of dysmorphic features (minor physical and dermal abnormalities), movement abnormalities, and cortisol secretion on the developmental course of adolescents with SPD and other Axis II disorders. Participants will be followed for a four-year period to chart behavioral development, psychiatric symptoms and HPA activity. The resultant data will allow us to address key questions about the development and prediction of psychotic disorders in at-risk youth. In the long-term, the research holds promise for yielding findings that have implications for our conceptualization of the prodromal course of schizophrenia and other psychoses, and for approaches to preventive intervention.
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