Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
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Neuropsychopharmacology · Aug 1990
Comparative StudyTests of one-sided versus two-sided hypotheses in placebo-controlled clinical trials.
The p value associated with a test of significance is supposed to represent the probability of observed results given that the null hypothesis is actually true. In evaluating the efficacy of a new drug against placebo, regulatory considerations focus on superiority of the new drug over placebo. ⋯ Thus, the only probability of concern is the probability that apparent superiority of drug over placebo is a chance finding, and that is the probability associated with a one-tailed test. Where multiple studies must be evaluated with regard to the regulatory decision, meta-analytic considerations further support the relevance of one-sided p values.
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Neuropsychopharmacology · Jun 1990
A D2 dopamine receptor agonist disrupts sensorimotor gating in rats. Implications for dopaminergic abnormalities in schizophrenia.
Prepulse inhibition of acoustic startle is deficient in schizophrenic patients and in animals injected with either direct or indirect dopamine (DA) agonists. The present experiments confirmed the hypothesis that the dopaminergic blockade of prepulse inhibition is attributable to the activation of D2 DA receptors. After systemic administrations of the D1 agonist SK&F 38393, the D2 agonist quinpirole, or a combination of the two, rats were tested for prepulse inhibition of the startle response by presenting acoustic stimuli or acoustic stimuli preceded by weak prepulses that inhibit startle. ⋯ When an ineffective dose of quinpirole (0.1 mg/kg) was coadministered with 10.0 mg/kg SKF 38393, prepulse inhibition was reduced relative to saline controls. This reduction of prepulse inhibition is consistent with the synergistic effect of D1 and D2 DA receptor stimulation noted in studies of dopaminergic influences on stereotyped behavior in rats. These findings confirm that a disruption of sensorimotor gating results from D2 dopaminergic stimulation in the rat and extend the applicability of this animal model for the similar behavioral deficits exhibited by schizophrenic patients.
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Neuropsychopharmacology · May 1989
Free and conjugated plasma homovanillic acid in schizophrenic patients.
It has recently been suggested that the plasma level of homovanillic acid (HVA) may provide an index of central dopaminergic activity in humans. Clinical studies have shown that in schizophrenic patients, plasma HVA levels increase with the severity of psychopathology. However, these studies only considered the plasma free HVA fraction whereas investigations on conjugated HVA in humans are sparse and results remain controversial. ⋯ No significant correlations were observed between plasma HVA levels and the clinical features of schizophrenic patients rated by various psychiatric scales. These findings suggest that there is an imbalance between plasma free and conjugated HVA in schizophrenic patients, who present an increase in total HVA when compared with controls. Paranoid schizophrenic patients, who present mainly positive symptoms, show the most marked plasma free/conjugated HVA imbalance.
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If, as hypothesized, neuroactive peptides from grain glutens are the major agents evoking schizophrenia in those with the genotype(s), it should be rare if grain is rare. To test this, we analyzed the results of our clinical examinations (e.g., kuru) and observations of anthropologists on peoples consuming little or no grain. ⋯ When these peoples became partially westernized and consumed wheat, barley beer, and rice, the prevalence reached European levels. Our findings agree with previous epidemiologic and experimental results indicating that grain glutens are harmful to schizophrenics.