Dopamine Turnover in Schizophrenia Before and after Haloperidol Withdrawal Cathy House

Dopamine Hypothesis of Schizophrenia Attributes symptoms of schizophrenia to a disturbed and hyperactive dopaminergic signal transduction. Increased dopamine activity considered a major factor of psychotic symptoms.

Antipsychotic drugs such as chlorpromazine block dopamine receptors Haloperidol is an antipsychotic used in the treatment of schizophrenia and in the treatment of acute psychotic states and delirium.

The Study Hypothesis: Dopamine metabolite homovanillic acid (HVA) should change with drug withdrawal. Study of cerebrospinal fluid (CSF), plasma and urinary HVA on and off haloperidol. Samples were obtained in 72 physically healthy schizophrenic males with mean age 36 ± 7.4 years before and after haloperidol withdrawal.

Experimental Control Only patients who had been treated for at least 6 months with antipsychotic drugs and who had experienced at least two previous relapses were invited to participate. Those with risk of suicide or severe violence were excluded. If patients were not treated with haloperidol, they were switched to this drug for at least 2 months prior to testing. Patients adhered to a low-monoamine, caffeine-restricted and alcohol-free diet.

Measurements Lumbar puncture (LP), blood draws and urine collection were done. Focus on Urinary HVA concentration. HVA was determined with high-pressure liquid chromatography (HPLC).

Statistical Analysis ANOVA or Paired t-tests were used to analyze differences between groups. What do you suspect were the original hypotheses? Ho: µd = 0 Ha : µd ≠ 0 Ho: µ1 = µ2 Ha: µ1 ≠ µ2

F Test vs. Paired Test F statistic provides a test for the statistical significance of the observed difference among the means of two or more random samples Paired t-test is used to compare means on the same or related subject over time or in differing circumstances. Which test would have been more appropriate? A paired t-test seems to make more sense than F P-values obtained with ANOVA are same as those you’d get if you called it a pooled two-samples t but NOT necessarily the same as the paired p-values.

Results

Summary of Data Overall CSF HVA values for ALL 72 subjects: (before) 30.95 ± 15.18 ng/ml vs (after) 27.17 ng/ml (combined means and S.D.’s for relapsed and non-relapsed individuals into one overall mean and S.D.) F = 6.94 df = (1, 70) Is that F- value large? Yes. Will the p-value be small? Yes. p = .01 Reject hypothesis that there was no effect?

Conclusions Supports the hypothesis that CSF HVA values were significantly lower AFTER haloperidol withdrawal than before. Data indicates that haloperidol withdrawal markedly decreased HVA function and excretion in schizophrenic patients. CSF HVA declined with drug withdrawal regardless of clinical change.