The purpose of these studies is to determine the importance of free radical mechanisms in tardive dyskinesia (TD). Free radicals are cytotoxic substances containing one or more unpaired electrons. In recent years a number of different movement disorders have been proposed to be associated with free radical formation. Some of these disorders include Parkinson""""""""s disease, manganese-induced hyperkinesias, Hallervorden-Spatz disease, and MPTP-induced parkinsonism. In order to determine if free radicals are involved in the pathophysiology of TD, both human and animal experiments will be performed. In one set of experiments, the cerebrospinal fluid of patients on neuroleptics with and without TD will be measured for evidence of free radical activity. Additionally, alpha-tocopherol (vitamin E), a nontoxic free radical scavenger that crosses the blood-brain barrier, will be employed. The only known action of alpha-tocopherol is free radical scavenging. Patients with TD will be treated with a-tocopherol is free radical scavenging. Patients with TD will be treated with alpha-tocopherol to determine if such treatment reduces the severity of movement disorder. In the second set of experiments, alpha-tocopherol will be administered to rats treated long-term (up to one year) with the neuroleptic fluphenazine decanoate to determine if treatment with alpha-tocopherol reduces the incidence and severity of neurochemical (including measures of free radical activity) and neuropathological changes induced by neuroleptics. These experiments may furnish insight into the pathophysiological basis of TD and TD-like movement disorders, and may provide a viable treatment for some patients who develop the condition.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29MH045142-03
Application #
3475196
Study Section
Treatment Development and Assessment Research Review Committee (TDA)
Project Start
1989-08-01
Project End
1994-07-31
Budget Start
1991-08-01
Budget End
1992-07-31
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Lohr, J B; Caligiuri, M P (1996) A double-blind placebo-controlled study of vitamin E treatment of tardive dyskinesia. J Clin Psychiatry 57:167-73
Lohr, J B; Caligiuri, M P (1995) Motor asymmetry, a neurobiologic abnormality in the major psychoses. Psychiatry Res 57:279-82
Caligiuri, M P; Lohr, J B; Vaughan, R M et al. (1995) Fluctuation of tardive dyskinesia. Biol Psychiatry 38:336-9
Tsuang, J W; Lohr, J B (1994) Effects of alcohol on symptoms in alcoholic and nonalcoholic patients with schizophrenia. Hosp Community Psychiatry 45:1229-30
Rapaport, M H; Lohr, J B (1994) Serum-soluble interleukin-2 receptors in neuroleptic-naive schizophrenic subjects and in medicated schizophrenic subjects with and without tardive dyskinesia. Acta Psychiatr Scand 90:311-5
Lohr, J B; Flynn, K (1993) Minor physical anomalies in schizophrenia and mood disorders. Schizophr Bull 19:551-6
Caligiuri, M P; Lohr, J B; Panton, D et al. (1993) Extrapyramidal motor abnormalities associated with late-life psychosis. Schizophr Bull 19:747-54
Caligiuri, M P; Lohr, J B; Jeste, D V (1993) Parkinsonism in neuroleptic-naive schizophrenic patients. Am J Psychiatry 150:1343-8
Caligiuri, M P; Lohr, J B (1993) Worsening of postural tremor in patients with levodopa-induced dyskinesia: a quantitative analysis. Clin Neuropharmacol 16:244-50
Jeste, D V; Lohr, J B; Manley, M (1992) Study of neuropathologic changes in the striatum following 4, 8 and 12 months of treatment with fluphenazine in rats. Psychopharmacology (Berl) 106:154-60

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