Absent response to niacin skin patch is specific to schizophrenia and independent of smoking
Introduction
Flushing of the face and trunk has been reported in 92% to 100% of patients receiving oral nicotinic acid treatment for hyperlipidemia (Mosher, 1970). The vasodilatory response was caused by stimulating the release of prostaglandin (PG), in particular, PGD2 from the skin (Morrow et al., 1989, Morrow et al., 1992). Absent or diminished flush responses in schizophrenic patients after niacin intake was first reported by Hoffer (1962) and was proposed as a possible simple biochemical test for schizophrenia by Horrobin (1980). Although two subsequent studies failed to replicate these findings (Fiedler et al., 1986, Wilson and Douglass, 1986), this has been attributed to using too low a dose of NA (Hudson et al., 1997). However, using a higher 200 mg dose of NA, Rybakowski and Weterle (1991) and Hudson et al., 1997, Hudson et al., 1999 reported that approximately 25–40% of schizophrenic patients showed no vasodilatory response.
Ward et al. (1998) observed a diminished flush response to topically applied methyl nicotinate in about 83% of schizophrenic patients using visual inspection for assessment of flush responses. Several follow-up studies using the same method also demonstrated impairment to topically applied methyl nicotinate in schizophrenic patients, though the proportion of impairment was not so high (Shah et al., 2000, Puri et al., 2001, Puri et al., 2002, Maclean et al., 2003). One study failed to show a significantly higher prevalence for absent flush responses to topical niacin in schizophrenic patients (Tavares et al., 2003). The studies using other methods for assessment of flush responses also revealed significantly diminished flush responses in schizophrenic patients, including those using laser Doppler flowmetry (Messamore et al., 2003, Ross et al., 2004a) and those using optical reflection spectroscopy (Smesny et al., 2001, Smesny et al., 2003, Smesny et al., 2005).
Whether the abnormal skin flush response to niacin is present only in schizophrenic patients, and not in bipolar patients, remains unclear. Bipolar patients were reported to have either an accentuated flush response to oral NA (Hudson et al., 1997) or an attenuated response to topical methyl nicotinate (Maclean et al., 2003). In addition, a significantly higher prevalence of cigarette smoking was present in schizophrenia than in the normal population (Hughes et al., 1986, Fowler et al., 1998). A possible effect of nicotine on niacin response was first considered by Vaddadi (1981) due to the similarity of niacin and nicotine. Therefore, its possible confounding effect upon the abnormal niacin skin flush in schizophrenia should be considered.
The samples of the above studies come mainly from Caucasian subjects. It is unclear if the phenomenon of diminished responses to niacin skin patch in schizophrenic patients is also present in the samples of different ethnic background.
This study investigated the differences in niacin skin flush responses between patients with schizophrenia, bipolar affective disorder, and normal controls, and it also examined the confounding effect of smoking on niacin skin flush responses in a sample of ethnic background other than Caucasian.
Section snippets
Subjects
Three groups of subjects, schizophrenic patients, bipolar manic patients, and healthy controls, were recruited. All subjects were required to meet the inclusion criteria of no past history of drug and food allergy, no major systemic illness (especially heart disease, autoimmune disease, and severe allergic disease such as asthma and severe skin allergic disease), and no use of steroid and non-steroid anti-inflammatory drugs within a week before niacin skin test. Sixty-one patients who met the
Results
The initial ANOVA including all data revealed a significant interaction between DISEASE and CONCENTRATION (F4, 232 = 11.2, P < 0.001, ε = 0.801), indicating that the differences of flush responses among three disease groups depend on the methyl nicotinate concentrations used. Subsequent repeated measures two-way ANOVA with TIME as the within-subject factor and DISEASE as the between-subjects factor under three concentrations revealed significant main effects of DISEASE at the concentrations of 0.1 M (
Discussion
Our study results suggest that the absent response to the niacin skin patch is specific to schizophrenia and independent of nicotine use. Our study also demonstrated that the assessment of skin flush response by visual inspection using a 4-point score could be performed with satisfactory reliability, indicating its potential practical value as a clinical examination. The test parameters of niacin concentration of 0.01 M and assessment of skin response at 10 min after application were best able
Acknowledgements
This research was supported by the grants from the National Health Research Institute (NHRI-CN-MG-9006S; NHRI-EX93-9113PP), the National Taiwan University Hospital (NTUH-90S1562), and the NRPGM, National Science Council, Taiwan (NSC-93-3112-B-002-012).
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