This proposal addresses critical long-standing questions regarding the nature and origin of choreoathetoid movement disorders in schizophrenia by comparing a group of Moroccan schizophrenics who have a long duration of illness but who have never received neuroleptic medication (NM), to matched groups of chronically-medicated (CM) schizophrenics and non- patient controls (NC). (1) Do choreoathetoid movements in schizophrenia appear as a function of the disease process? (2) Do these movement appear as a function of age or duration of illness? (3) Does the appearance of choreoathetoid movements prior to treatment with neuroleptic medications indicate a vulnerability to subsequent development of neuroleptic-induced tardive dyskinesia (TD)? (4) Do schizophrenics who experience long- duration untreated illness show increased cognitive deficits in comparison to patients who have received treatment early in the course of illness? (5) Do schizophrenics who experience long-duration untreated illness show decreased regional brain volumes in comparison to patients who have received treatment early in the course of illness? This study is a unique opportunity to examine a rare population of 100 to 1509 never-medicated DSM-III R schizophrenics as they present for treatment at the Psychiatric Center in Casablanca, Morocco. Prior to treatment, patients will be examined for the presence of choreoathetoid and Parkinsonian movements, and will be given a battery of neuropsychological tests to assess current cognitive functioning. After stabilization on neuroleptic medication, patients will be reexamined for both movements and cognitive function. Patients will also undergo similar reexaminations at one- and two-year intervals. Both Moroccan and U.S. groups will be examined to control for cultural and socioeconomic influences on outcomes. The same battery of examinations given to the never-medicated schizophrenics will also be given to matched comparison groups of chronically-medicated inpatient schizophrenics, recruited form the inpatient wards at the Casablanca Center, the Portland VAMC, and OHSU. Base rates of spontaneous dyskinesias will estimated by applying the same examination to community normal control groups in Casablanca and Portland. All groups will also receive CT scans for volumetric quantification of brain regions. The data will be analyzed by ANOVA, and repeated-measures ANOVA and MANOVA for follow-up data. Planned comparisons showing CM> NM> NC for movement scores will confirm the main hypotheses. Comparisons for cognitive functioning and volumetric analysis are expected to yield NM < CM < NC. Cognitive functioning for NM patients is expected to improve after medication and stabilize below CM levels. The presence of movements in NM patients is expected to predict a vulnerability for subsequent TD.
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