Dopamine Turnover in Schizophrenia Before and after Haloperidol Withdrawal - PowerPoint PPT Presentation

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Dopamine Turnover in Schizophrenia Before and after Haloperidol Withdrawal

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Dopamine Turnover in Schizophrenia Before and after Haloperidol Withdrawal Cathy House Dopamine Hypothesis of Schizophrenia Attributes symptoms of schizophrenia to a ... – PowerPoint PPT presentation

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Title: Dopamine Turnover in Schizophrenia Before and after Haloperidol Withdrawal


1
Dopamine Turnover in Schizophrenia Before and
after Haloperidol Withdrawal
  • Cathy House

2
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.

3
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.

4
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.

5
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.

6
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).

7
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

8
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
    youd get if you called it a pooled two-samples t
    but NOT necessarily the same as the paired
    p-values.

9
Results
10
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.

11
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.
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