Early phase psychotic illness and putative prodromal states represent enormous challenges and opportunities. The challenges include diagnostic uncertainty in an age range which is critical to maturation and individuation and fraught with psychological and social stresses. The opportunities include the ability to intervene appropriately, effectively and consistently in order to have a profound impact on long-term individual and public health disease consequences. In our Principal Research Core we are/will be conducting an extensive series of studies in this context. The theme is to inform treatment decisions and this requires involving all of the units in the Operations Core as well as the units in the Methods Core. We have selected to present, as examples, several planned studies which fit the description of R-34-like development projects. These projects, as suggested by the Program Announcement, are intended to provide preliminary data to guide the design of future, more definitive investigations. We have selected examples which illustrate the range of related, but distinct, issues that Center investigators will address in keeping with our theme. We have also provided a selected array of planned pil ot studies, particulariy those involving young investigators. The study of the potential role of antidepressants in the treatment of the putative schizophrenia prodrome will provide controlled data following up exciting findings obtained in open naturalistic treatment. In addition, this trial and it's results will relate to the adherence issue in that we have found the target population to be more accepting of antidepressants than of antipsychotics. It also relates to the adverse effects challenges, because antidepressants have very different risk profiles compared to antipsychotics. The role of the clinical assessment unit is critical in both identifying appropriate subjects, but also ensuring that any clinical predictors associated with preferential response to one class of agents or another are well-captured. Similariy, the biomarker unit can help to inform biological and other predictors and mediating variables which will ultimately inform treatment decisions and provide clues to basic mechanism(s). The treatment of substance-induced psychotic disorder has not received adequate attention. Do such individuals require antipsychotic treatment to prevent recurrence of psychosis? Are these in fact, individuals with a heightened vulnerability/diathesis toward psychotic disorders? All of the units in the Center come into play in addressing this question and the Center projects and data base facilitate important comparisons with patients whose prodromal symptoms and/or psychoses are not complicated by seeming substance use precipitation of psychotic signs and symptoms. Similariy, the presence of psychotic symptoms in young individuals with bipolar disorder raises questions about diagnosis and diagnostic stability as well as important decisions about the potential long-term use of issues affecting this population. Again the potential role of biomarkers and clinical predictors in this context cannot be overemphasized. The availability of a longitudinal data base on well-characterized bipolar patients with psychotic disorders enables us to use trajectory and symptom based clustering in addition to traditional diagnostic approaches. In any situation where drugs which affect weight regulation and metabolic parameter are potentially used, we need to have a better understanding of preventive and management strategies. We have chosen a particularly vulnerable (on many levels) population (i.e. early onset schizophrenia) to study a strategy or risk reduction. This project also draws on the resources and guidance of all of the Center's Units, and the data will be valuable in managing any patients who might be treated with drugs affecting metabolism. Finally, we propose a project focusing on method advancement that involves the development of an appropriate functional battery for eariy phase illness. This battery involves the assessment of both social and role functioning, utilizing measures of competence versus achievement to differentiate key aspects mediating functional disability in eariy phase patients.
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