Subsensitivity to the skin flush effect of niacin is among the most reliable and widely-replicated peripheral physiological abnormalities in schizophrenia. However, the mechanism and significance of this abnormality has not been described. Since the flush response to niacin is mediated by vasodilatory prostaglandins that are derived from arachidonic acid, one possible mechanism for niacin subsensitivity in schizophrenia relates to reduced arachidonic acid levels. Low levels of arachidonic acid in cell membranes from the brain as well as from the red blood cells have been consistently observed in schizophrenia. This study will test the hypothesis that niacin subsensitivity in patients with schizophrenia is a functional marker of low membrane arachidonic acid levels. A secondary goal of the study is to determine if low arachidonic acid levels and/or low niacin sensitivity are related to the expression of symptoms or the severity of illness in patients with schizophrenia. We will quantify cutaneous niacin sensitivity by measuring the skin blood flow response to graded doses of topical alpha-methylnicotinate (AMN). Laser Doppler flowmetry will be used to quantify blood flow response and niacin sensitivity will be defined by the EC50 value for AMN. Symptom expression and illness severity will be assessed by the Positive and Negative Synfrome Scale, Global Assessment of Function, and Strauss-Carpenter scales. The data will help to determine whether niacin subsensitivity in schizophrenia is a marker of arachidonic acid deficiency, and will help to determine whether arachidonic acid deficiency and/or niacin subsensitivity are related to aspects of symptom expression or illness severity in schizophrenia.
| Messamore, Erik (2012) Niacin subsensitivity is associated with functional impairment in schizophrenia. Schizophr Res 137:180-4 |
| Messamore, Erik; Hoffman, William F; Yao, Jeffrey K (2010) Niacin sensitivity and the arachidonic acid pathway in schizophrenia. Schizophr Res 122:248-56 |
