Niacin sensitivity and the arachidonic acid pathway in schizophrenia

Abstract

Objective-Schizophrenia is associated with a blunted flush response to niacin. Since niacininduced skin flushing is mediated by vasodilators derived from arachidonic acid (AA), we tested whether the blunted flush response to niacin is a marker of AA deficiency.Methods-Eight concentrations of methylnicotinate were applied to the forearms of 20 adults with schizophrenia and 20 controls. Laser Doppler measurement of blood flow responses was used to derive values for niacin sensitivity (defined as the concentration eliciting half-maximal response, i.e., EC 50 value) and efficacy (defined as the maximal evoked blood flow response). RBC membrane fatty acids were analyzed by gas chromatography.Results-Niacin sensitivity and efficacy were reduced in schizophrenia. In the control group, there was significant correlation between AA levels and niacin sensitivity as well as a trend toward correlation between AA levels and niacin efficacy. In contrast, neither sensitivity nor efficacy of niacin correlated with AA levels in schizophrenia. An expected correlation between the levels of AA and its elongation product (adrenic acid) was absent in schizophrenia. Adrenic acid levels correlated with niacin efficacy in schizophrenia.Conclusions-The schizophrenia-associated niacin response abnormality involves both diminished sensitivity and reduced efficacy. The lack of expected correlation between levels of AA and adrenic acid suggests homeostatic imbalance within the n-6 polyunsaturated fatty acid (PUFA) pathway in schizophrenia. Though AA levels were unrelated to measures of niacin response in schizophrenia, the correlation between adrenic acid and niacin efficacy in schizophrenia suggests relevance of the n-6 PUFA pathway to the blunted niacin response.

Phospholipid, arachidonate and eicosanoid signaling in schizophrenia

“…Similarly, it appears that nicotine use has no effect on the niacin-induced flushing response (Chang et al, 2009;Liu et al, 2007;Messamore, 2003Messamore, , 2010Ross et al, 2004;Shah et al, 2000;Smesny et al, 2003). Our recent findings (Yao et al, 2015) also support the notion that niacin sensitivity is not significantly affected by smoking.…”

“…However, this expected correlation is abolished in SZ (Messamore et al, 2010). Similar precursor-product dysregulations have also shown in tryptophan (Yao et al, 2010b) and purine (Yao et al, 2010a) pathways.…”

“…Although lower AA levels were found in patients who did not flush in response to oral niacin (Glen et al, 1996), no correlation between AA levels and niacin response was observed in two different groups of patients with SZ (Maclean et al, 2003;Messamore et al, 2010). On the other hand, an unexpected correlation was observed between maximal niacininduced blood flow and red blood cell membrane levels of adrenic acid (22:4 n-6), the elongation product of AA.…”

“…Lower RBC membrane AA levels are associated with decreased niacin sensitivity, but this expected correlation has only been described in a healthy control group (Messamore et al, 2010). Although lower AA levels were found in patients who did not flush in response to oral niacin (Glen et al, 1996), no correlation between AA levels and niacin response was observed in two different groups of patients with SZ (Maclean et al, 2003;Messamore et al, 2010).…”

“…This paper will describe how arachidonic acid (AA) and abnormalities related to its metabolism may to some extent unify some seemingly unrelated biochemical findings in SZ (Horobin, 1998;Skosnik and Yao, 2003). We will also describe how a blunted skin flush response to niacin may serve as a biomarker for AA-related signaling defects, and suggest that AA-related abnormalities may represent a distinct physiological subtype within the SZ syndrome (Messamore, 2003;Messamore et al, 2010;Yao et al, 2015). Skosnik and Yao, 2003).…”