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We measured the dopamine metabolite homovanillic acid (HVA) in cerebrospinal fluid (CSF) before and after probenecid administration in normal controls and in patients with Huntington's disease. Baseline CSF HVA concentrations correlated positively with age in normal control subjects. Baseline CSF HVA concentrations were reduced in patients with Huntington's disease, and the degree of this reduction correlated with the severity of dementia and with the duration of disease. These results suggest that changes in the metabolism of dopamine by dopaminergic neurons may be associated with the dementia of Huntington's disease as well as with normal aging. These changes in dopaminergic functioning are apparently different in Huntington's disease than in normal aging and can be detected by measuring CSF HVA concentration.

With the discovery of the opiate peptides, several major avenues of research became apparent. These peptides produced a great deal of focused attention on their anatomy, biochemistry, and physiology. In this article, we present an overview of some of the main research issues and recent findings in the field of opiate peptides. The possible relationship of the opiate peptide neuronal systems to schizophrenia is discussed in light of attempts to alter schizophrenic symptoms with opiate antagonists, beta-endorphin, and dialysis. It is hypothesized that if the opiate peptides are involved in schizophrenia, then their involvement with dopamine systems and/or with stress responses may be critical.

To study the effects of beta-endorphin in chronic schizophrenia, nine male patients participated in a double-blind crossover comparison of a single intravenous 20-mg injection of beta-endorphin and saline. Bolus injection of beta-endorphin from an albumin-coated syringe produced markedly higher plasma concentrations than did slow intravenous infusion from a non-albumin-coated syringe. Beta-endorphin intravenously injected in nine patients produced a statistically significant increase in serum prolactin levels. In one patient, both 10 mg of morphine sulfate and 20 mg of beta-endorphin produced similar increases in the alpha power of the EEG. In eight patients, beta-endorphin administration was associated with a statistically significant but not clinically obvious improvement in schizophrenic symptoms.

A case of a folate-responsive psychosis that was associated with a defect in N5-10-methylenetetrahydrofolate reductase (methylene reductase) suggested the need to examine whether abnormally low activity of this enzyme might be of etiological importance in schizophrenia. We now report that there were no statistically significant differences in the platelet methylene reductase activity of chronic schizophrenics, compared with either hospitalized or nonhospitalized age-matched control subjects. Although it is possible that a larger survey might reveal a subpopulation of schizophrenics who are characterized by abnormal methylene reductase activity, this study suggests that chronic schizophrenia is not generally associated with such changes.