There is now considerable evidence that anatomic pathology is present at the first episode of schizophrenia.Little research has been directed at understanding whether these anatomic deficits and their longitudinalcourse can be used to predict treatment response and neuropsychological and functional outcomemeasures. The identification of patients early in the course of illness who are nonresponsive to standardantipsychotic treatment could have significant implications for pharmacologic intervention and strategies forimproving subsequent prognosis. Neurobiological predictors of treatment response in schizophrenia havenot been well defined, however, and this phenomenon has no clear neurobiological basis, although a defectin the brain gray matter has been implicated. Moreover, recent empirical and theoretical work suggests thata defect in the brain white matter may be a contributing factor to antipsychotic nonresponse in schizophrenia.The investigation of neurobiological predictors in schizophrenia has been limited in large part due to the lackof controlled clinical trials from which to recruit patients and test hypotheses regarding response. Ourpreliminary data suggest that prefrontal gray matter deficits, as assessed via cortical surface mappingmethods, predict treatment response in patients with first episode schizophrenia. Additional preliminary datasuggest that lower fractional anisotropy, as assessed via diffusion tensor imaging, in frontotemporal regionsis associated with treatment nonresponse in these patients. In the present study we propose scanning aunique group of 75 antipsychotic drug-naTve, first episode schizophrenia patients. Patients will be drawnfrom an NIMH-sponsored (2R01-MH60004) double-blind randomized 12-week trial of risperidone vs.aripiprazole, and followed with regular assessments under controlled treatment as part of the CIDAR clinicalalgorithm for one year.
The specific aims of this study are to: (1) determine the relationship between corticalgray matter volume/density and white matter fractional anisotropy in first episode patients with schizophreniaand treatment response/outcome following the 12 week randomized clinical trial and after 52 weeks ofcontrolled treatment; and (2) examine changes in gray matter volume/density and white matter fractionalanisotropy in first episode patients over the 12 week randomized clinical trial and after 52 weeks of controlledtreatment in relationship to treatment response/outcome. The identification of these abnormalities at the firstepisode of illness may be useful for identifying indicators of vulnerability, which may lead to improved earlydentification of individuals at risk for schizophrenia.
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