Attenuated niacin-induced skin flush response in individuals with clinical high risk for psychosis

Abstract

Background: Impaired sensitivity of the skin flush response to niacin is one of the most replicated findings in patients with schizophrenia. However, prior studies have usually focused on postonset psychosis, and little is known about the clinical high-risk (CHR) phase of niacin sensitivity in psychosis.

Aims: To profile and compare the niacin flush response among CHR individuals (converters and non-converters), patients with first-episode schizophrenia (FES) and healthy controls (HCs).

Methods: Sensitivity to four concentrations (0.1-0.0001 M) of aqueous methylnicotinate was tested in 105 CHR individuals, 57 patients with FES and 52 HCs. CHR individuals were further grouped as converters and non-converters according to the 2-year follow-up outcomes. Skin flush response scores were rated on a 4-point scale.

Results: Of the 105 CHR individuals, 21 individuals were lost during the study, leaving 84 CHR individuals; 16 (19.0%) converted to full psychosis at 2 years of follow-up. Flush response scores identified in the CHR samples were characterised as modest degree levels, intermediate between those of HC individuals and patients with FES. The flush responses in the CHR group mimicked the responses observed in the FES group at higher concentrations (0.01 M, 0.1 M) and longer time points (15 min, 20 min); however, these became comparable with the responses in the HC group at the shorter time points and at lower concentrations. The converters exhibited lower mean flush response scores than the non-converters.

Conclusions: Attenuated niacin-induced flushing emerged during the early phase of psychosis. New devices should be developed and verified for objective quantification of skin responses in the CHR population.

Keywords: schizophrenia.

Figure 1

The mechanism of niacin-induced skin flushing. AA, arachidonic acid; COX, cyclo-oxygenase; Ca²⁺, calcium; PGD₂, prostaglandin D₂; PGE₂, prostaglandin E₂; PGG₂, prostaglandin G₂; PGH₂, prostaglandin H₂; PLA₂, phospholipase A₂.

Figure 2

Flowchart showing study subjects selection. CHR, clinical high risk; FES, first-episode schizophrenia; HC, healthy controls.

Figure 3

A dot and line figure of means of the flush scores in niacin skin tests at four concentrations of AMN and at each time point in HCs, subjects with CHR and patients with FES. Note: Differences in the flush scores in niacin skin were presented. P values were calculated by MANOVA with age and education as covariates. AMN, aqueous methylnicotinate; CHR, clinical high risk; FES, first-episode schizophrenia; HCs, healthy controls; MANOVA, multivariate analysis of variance.

Figure 4

A dot and line figure of means of the flush scores in niacin skin tests at four concentrations of AMN and at each time point in converters and non-converters for subjects with CHR. Note: Differences between converters and non-converters in the flush scores in niacin skin were presented. P values were calculated by the MANOVA test. AMN, aqueous methylnicotinate; CHR, clinical high risk; MANOVA, multivariate analysis of variance.