Niacin sensitivity and the arachidonic acid pathway in schizophrenia.
OBJECTIVE
Schizophrenia is associated with a blunted flush response to niacin. Since niacin-induced 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.
Messamore
Erik
E
Behavorial Health and Clinical Neurosciences Division, Portland VA Medical Center, Portland, OR 97239, USA. Erik.Messamore@va.gov
Hoffman
William F
WF
Yao
Jeffrey K
JK
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004883:Erucic Acids / Q000378:metabolism; D043371:Fatty Acids, Omega-6 / Q000378:metabolism; D005231:Fatty Acids, Unsaturated; D005260:Female; D005483:Flushing / Q000139:chemically induced / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009525:Niacin / Q000494:pharmacology*; D009539:Nicotinic Acids / Q000494:pharmacology; D012044:Regression Analysis; D012559:Schizophrenia / Q000097:blood / Q000503:physiopathology*; D012867:Skin / Q000098:blood supply / Q000187:drug effects; D012882:Skin Tests
D000893:Anti-Inflammatory Agents; D004883:Erucic Acids; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D009539:Nicotinic Acids; C011395:adrenic acid; D009525:Niacin; D016718:Arachidonic Acid; C008473:methyl nicotinate