The niacin skin flush abnormality in schizophrenia: a quantitative dose-response study

Niacin dilates cutaneous blood vessels, resulting in a pronounced skin flush in most people. The flush response to niacin is attenuated in schizophrenia, but the quantification and physiological mechanism of this abnormality have not been described in detail. It is not clear whether the mechanism involves changes in the pharmacological sensitivity to niacin, or whether there is a reduced ability of the vasculature to dilate adequately in subjects with schizophrenia. We address this question in the present study by characterizing the dose-response relationship between topically applied alpha-methylnicotinate (AMN) and cutaneous blood flow changes, which were quantified by laser Doppler flowmetry. The dose-response curve was shifted to the right in subjects with schizophrenia. The EC(50) value of AMN was significantly increased in the schizophrenia group (mean: 1.66 mM; 95% confidence interval: 1.04-2.65 mM) as compared to the control group (mean: 0.38 mM; 95% confidence interval: 0.263-0.547 mM). The blood flow responses to higher AMN doses were lower in the schizophrenics; however, there was no statistically significant difference in the extrapolated maximal blood flow response value (F(max)) between the two groups. The results suggest that the skin flush abnormality in schizophrenia primarily reflects reduced pharmacological sensitivity to niacin rather than an inadequate cutaneous vasodilatory response to the stimulus. Since vasodilatation in response to niacin requires the release of prostaglandins, the data from this study suggest that schizophrenia is associated with abnormalities in enzymes, receptors, or signal transduction mechanisms that affect the synthesis, release, or response to vasodilatory prostaglandins.