The Relationship between Impaired Methylnicotinate Response and Oxidative Stress in Schizophrenia

Brian M Ross,Iain Glen

doi:10.4236/ojpsych.2014.42018

Abstract

MNA response applied methylnicotinate (MNA) results in an arachidonic acid and cyclooxygenase-dependent vasodilatatory response which is diminished in patients with schizophrenia. This observation has been suggested to form the basis of a diagnostic test for the illness although the potential utility of such a procedure is diminished since the underlying mechanism is unclear. In this study we sought to discover if reduced MNA response in schizophrenia is related to increased oxidative stress i.e. whether or not the two measures are negatively correlated with each other. MNA response was assessed visually in 17 patients with schizophrenia and 16 healthy controls and compared to the extent of oxidative stress in each participant assessed by quantifying the lipid peroxidation product ethane in breath. Serum vitamin E, a lipid soluble antioxidant, concentrations was also assessed. While MNA response was correlated with breath ethane concentrations, the expected relationship between the two measures was not observed. Instead a positive relationship between them suggests that some patients with schizophrenia have impaired fatty acid utilization leading to both diminished lipid peroxidation and cyclo-oygenation. This was not related to vitamin E concentrations, however, suggesting that lipid soluble anti-oxidant availability did not underlie our findings. Our data shed further light on the mechanism of impaired MNA response in schizophrenia and support the notion that this occurs consequent to a change in lipid metabolism.

Highlights

Schizophrenia is a common mental illness affecting approximately 1% of the world’s population [1]
methyl nicotinate (MNA) response was not correlated with serum vitamin E concentration but was significantly correlated with breath ethane concentrations (P < 0.05) in the schizophrenia group (Figure 1) but, contrary to the hypothesized negative correlation, the correlation was positive (Pearson correlation coefficient = 0.76) i.e. reduced MNA response is associated with lower breath ethane concentration rather than higher
While the average extent of oxidative stress may be elevated in schizophrenia as suggested by our own and many other studies, our results suggest that oxidative stress is lower or even normal in patients who exhibit the greatest impairment of MNA-induced vasodilatation

Summary

Introduction

Schizophrenia is a common mental illness affecting approximately 1% of the world’s population [1]. Schizophrenia is likely caused by the interplay of genetics and the environment leading to altered brain chemistry and/or structure [1], the major mechanism(s) responsible are unclear As such objective biologically based diagnostic tests for the disorder are unavailable. PGD2 diffuses from the Langerhan cell and acts via a second receptor present of the capillary wall to produce vasodilatation [5] It has been known for some time that patients with schizophrenia have a lesser or absent vasodilatatory response to oral NA assessed either visually or by measuring skin temperature [2] [3]. While a genetic linkage between MNA response and the membrane synthetic enzyme fatty acid CoA ligase in the healthy population does indicate an involvement of fatty-acid dependent signaling in the upstream Langerhan cell, precisely what makes patients with schizophrenia less responsive to NA eludes investigators [13] interest in the phenomenon remains [14] [15]

Methods

Results

Conclusion