Faculty Bibliography

The purpose of this study was to evaluate the hypothesis that neuroleptic non-response in the face of 'adequate' DA post-synaptic receptor blockade reflects failure of regulatory mechanisms to decrease DA pre-synaptic activity. Eight chronic schizophrenics, meeting rigorous criteria for neuroleptic non-response, were treated for four weeks with alpha-methylparatyrosine as an adjunct to their previously stable neuroleptic dose. Treatment with AMPT produced a prompt decrease in plasma HVA that was, on average, 72% lower at the end of the study. While there was also strong clinical evidence of reduction in central dopaminergic activity (both a significant reduction in dyskinetic movements and increase in extrapyramidal symptoms), there was virtually no change in severity of psychotic symptoms. Thus, in this group of non-responders, psychotic symptoms persisted despite both extensive dopamine post-synaptic receptor blockade and marked reduction of presynaptic activity. These symptoms may not be directly DA dependent

We measured serum phospholipase A2 (PLA2) activity in 39 schizophrenics, 26 psychiatric controls, and 26 normal controls using a radioenzymatic assay with phosphatidylcholine as precursor. Serum PLA2 activity was significantly higher in schizophrenics (p = 0.002) and other psychiatric (including substance abusing) patients (p = 0.032) than in normal controls. Enzyme activity did not differ between the schizophrenic patients and psychiatric controls. Fifty-one percent of the schizophrenics and 46% of psychiatric controls had PLA2 values above the highest value for normal controls. In the psychiatric control group higher than normal PLA2 activities were observed in all diagnostic categories, including major depression, bipolar disorder, posttraumatic stress disorder (PTSD), and substance abuse. In the context of others' findings of increased circulating PLA2 in infectious and inflammatory conditions, these increases must be viewed as disease nonspecific. The significance of these changes and their relationship to other acute-phase protein changes needs to be clarified in future research

Changes in plasma homovanillic acid (HVA) were investigated in neuroleptic responsive and nonresponsive schizophrenics in order to delineate parameters of dopamine regulation, which may underlie differences in neuroleptic responsivity. Nineteen schizophrenics were treated with haloperidol for 6 weeks. HVA was sampled at baseline, 24 hr after initial neuroleptic dose, and after 6 weeks of treatment. Subjects were pretreated with debrisoquin in order to reduce the peripheral production of HVA. The responders had an initial rise in HVA at 24 hr after first neuroleptic dose, followed by a decline back to baseline over the 6 weeks of treatment. The nonresponders' HVA failed to rise at 24 hr after first neuroleptic dose. At 6 weeks of treatment their HVA had fallen to significantly below baseline. Thus, a rise in HVA 24 hr after the first dose of neuroleptic predicted treatment response; a fall in HVA at 6 weeks to below pretreatment values was associated with neuroleptic nonresponse

OBJECTIVE: The authors studied the effects of vitamin E treatment of tardive dyskinesia; earlier studies have produced contradictory results. METHOD: Twenty-eight patients with tardive dyskinesia were treated in a double-blind, parallel-group comparison study of 8-12 weeks of treatment with vitamin E (1600 IU/day) or matching placebo capsules. RESULTS: The Abnormal Involuntary Movement Scale scores of the patients treated with vitamin E improved significantly compared to the scores of the patients given placebo. CONCLUSIONS: These results support earlier findings of the efficacy of vitamin E in treating tardive dyskinesia

Frontal lobe dysfunction is widely suspected to underlie negative symptoms of schizophrenia. This hypothesis is based largely on long-standing observations of the similarities between the effects of frontal lobe lesions and negative symptoms. However, there is little direct evidence specifically for such an association in schizophrenic patients. We measured the relationship between decreased relative prefrontal cortex glucose metabolism (hypofrontality) using positron emission tomography and evaluated the severity of negative symptoms in 20 chronic schizophrenics who underwent scanning while not receiving neuroleptic drugs. We found a close relationship between negative symptoms and prefrontal hypometabolism, particularly in the right dorsolateral convexity. This association was regionally specific. Furthermore, there was no evidence that this relationship was an artifact of age, cerebral atrophy, or severity of positive symptoms