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 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, caffeinerestricted 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: µ 1 = µ 2 • Ha: µ 1 ≠ µ 2 •
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? • Yes. •
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. •
Скачать презентацию Dopamine Turnover in Schizophrenia Before and after Haloperidol
bfedea35419194515e8287a153b8112d.ppt