Transcript Cathy`s Seminar

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.
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Increased dopamine activity considered a
major factor of psychotic symptoms.
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Antipsychotic Drugs
Antipsychotic drugs such as chlorpromazine block
dopamine receptors
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• 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.
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Study of cerebrospinal fluid (CSF), plasma and urinary
HVA on and off haloperidol.
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Samples were obtained in 72 physically healthy
schizophrenic males with mean age 36 ± 7.4 years
before and after haloperidol withdrawal.
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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.
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Measurements
Lumbar puncture (LP), blood draws and urine
collection were done.
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Focus on Urinary HVA concentration.
HVA was determined with high-pressure liquid
chromatography (HPLC).
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Statistical Analysis
ANOVA or Paired t-tests were used to analyze
differences between groups.
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What do you suspect were the original hypotheses?
•Ho: µd = 0
•Ha : µd ≠ 0
•Ho: µ1 = µ2
•Ha: µ1 ≠ µ2
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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
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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.
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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.
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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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