Dopamine-beta-hydroxylase in the cerebrospinal fluid: relationship to disulfiram-induced psychosis

Cerebrospinal fluid (CSF) dopamine-beta-hydroxylase (DBH) activity in 32 male alcoholics was measured using a modification of the radioenzymatic method of Molinoff et al. In most, the CSF was obtained before treatment with disulfiram, while in others it was obtained while they were on the drug (250 or 500 mg). As expected, treatment with this reversible DBH inhibitor had no effect on the activity of the enzyme measured in our in vitro assay. However, low pretreatment DBH activity was found to correlate with adverse reactions to disulfiram. Mean DBH activity of four individuals who went on to become psychotic on disulfiram was 0.13 +/- 0.02 nmole/ml per hr (mean +/- SEM). An additional four individuals who developed dysphoric but nonpsychotic reactions had a mean DBH of 0.23 +/- 0.03. Both these values were significantly lower than the mean DBH activity of the remaining 24 individuals treated with disulfiram who had no adverse side effects, 0.53 +/- 0.06 p less than 0.02 and p less than 0.05, respectively, 2-tailed t-test.