Little is known about the brain abnormalities associated with schizophrenia and related psychoses in late life. In the proposed research, we will use morphometric and qualitative analyses of magnetic resonance images (MRI) to examine qualitative and quantitative brain structural features that underlie late-life psychosis. The research will be guided by the following questions: (1) Are brain abnormalities different in quality or number in the various late-onset psychoses? In older schizophrenia patients: (2) Do brain abnormalities differ with age-of-onset? (3) How do brain abnormalities in older schizophrenia patients relate to clinical, psychosocial, or treatment outcomes? (4) How do the patterns of brain morphology in schizophrenia patients relate to impairments in executive function, information processing, and sensory gating? (5) Is there evidence for abnormalities in thalamo-cortical circuits that may be associated with schizophrenic symptomatology? Our working model is that schizophrenic symptomatology may be a result of dysfunction in the cortical-subcortical circuitry. This dysfunction may be due to problems in the functional balance between basal ganglia, thalamic, and cortical function, leading to dysfunction in cortical- subcortical circuits. Particular abnormalities in the relations among these structures may bear relationships to the particular clinical, neuropsychological and psychophysiological features exhibited by individual patients. Thus, the variety of brain abnormalities may be linked to the heterogeneous nature of symptomatology of schizophrenia and other psychoses in late life. Our findings thus far suggest that there may be specific brain morphometric differences between early-onset and late-onset forms of schizophrenia, particularly in the thalamus and in ventricle size. In the next funding period we will study larger numbers of subjects with varied ages of onset so that we can examine morphometric differences in greater detail. We will also attempt to understand the heterogeneity of behavioral disturbance in schizophrenia on the basis of brain morphology. In addition, we will formulate specific hypotheses that can be tested using functional imaging methods now in use (e.g., SPECT) or under development within our facilities (e.g., functional MRI). We will attempt to study all subjects from the Center. Subjects will receive MRI examinations, and all MRIs will be rated quantitatively for abnormalities. In addition, we will study a subset of schizophrenia and normal comparison subjects using quantitative MR image analytic methods that measure volumes of many cortical and subcortical brain regions. MRI measures will be related to age-of-onset, clinical features (including outcomes), and neuropsychological and psychophysiological function.
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