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Prevalence and Specificity of the Abnormal Niacin Response: A Potential Endophenotype Marker in Schizophrenia

The skin flush response to niacin is abnormally blunted among a subset of patients with schizophrenia (SZ), preferentially associates with SZ compared to other mental illnesses, occurs frequently in nonpsychotic members of SZ-affected families, appears heritable, and shows evidence of genetic associ...

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Autores principales: Yao, Jeffrey K., Dougherty, George G., Gautier, Clara H., Haas, Gretchen L., Condray, Ruth, Kasckow, John W., Kisslinger, Benjamin L., Gurklis, John A., Messamore, Erik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4753599/
https://www.ncbi.nlm.nih.gov/pubmed/26371338
http://dx.doi.org/10.1093/schbul/sbv130
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author Yao, Jeffrey K.
Dougherty, George G.
Gautier, Clara H.
Haas, Gretchen L.
Condray, Ruth
Kasckow, John W.
Kisslinger, Benjamin L.
Gurklis, John A.
Messamore, Erik
author_facet Yao, Jeffrey K.
Dougherty, George G.
Gautier, Clara H.
Haas, Gretchen L.
Condray, Ruth
Kasckow, John W.
Kisslinger, Benjamin L.
Gurklis, John A.
Messamore, Erik
author_sort Yao, Jeffrey K.
collection PubMed
description The skin flush response to niacin is abnormally blunted among a subset of patients with schizophrenia (SZ), preferentially associates with SZ compared to other mental illnesses, occurs frequently in nonpsychotic members of SZ-affected families, appears heritable, and shows evidence of genetic association. The niacin response abnormality (NRA) may prove to be a useful SZ endophenotype. Using a laser Doppler flowmeter, we undertook this study to estimate the prevalence of NRA in SZ (n = 70), bipolar disorder (BP, n = 59), and healthy control (HC, n = 87) groups, and to estimate its specificity for the illness. From the dose-response curves, we calculated the concentration of methylnicotinate required to elicit a half-maximal blood flow (MBF) response (EC(50) value) and MBF value for each subject. The median log(10)EC(50) of the SZ was above the third quartile of log(10)EC(50) of either the HC or BP groups, whereas the MBF was significantly lower in the SZ than in the HC or BP groups. With a definition of NRA of having both EC(50) above the ninetieth percentile of the control samples and MBF response below the sixtieth percentile for the control range, the NRA predicted SZ with 31% sensitivity and 97% specificity. Moreover, the NRA was not influenced by age, gender, race, and cigarette smoking. In summary, the NRA may define a SZ subtype with a clinically significant phospholipid signaling defect. Understanding its molecular origins may shed light on the pathophysiology of SZ and suggest new tools for its early diagnosis and treatment.
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spelling pubmed-47535992016-02-16 Prevalence and Specificity of the Abnormal Niacin Response: A Potential Endophenotype Marker in Schizophrenia Yao, Jeffrey K. Dougherty, George G. Gautier, Clara H. Haas, Gretchen L. Condray, Ruth Kasckow, John W. Kisslinger, Benjamin L. Gurklis, John A. Messamore, Erik Schizophr Bull Regular Article The skin flush response to niacin is abnormally blunted among a subset of patients with schizophrenia (SZ), preferentially associates with SZ compared to other mental illnesses, occurs frequently in nonpsychotic members of SZ-affected families, appears heritable, and shows evidence of genetic association. The niacin response abnormality (NRA) may prove to be a useful SZ endophenotype. Using a laser Doppler flowmeter, we undertook this study to estimate the prevalence of NRA in SZ (n = 70), bipolar disorder (BP, n = 59), and healthy control (HC, n = 87) groups, and to estimate its specificity for the illness. From the dose-response curves, we calculated the concentration of methylnicotinate required to elicit a half-maximal blood flow (MBF) response (EC(50) value) and MBF value for each subject. The median log(10)EC(50) of the SZ was above the third quartile of log(10)EC(50) of either the HC or BP groups, whereas the MBF was significantly lower in the SZ than in the HC or BP groups. With a definition of NRA of having both EC(50) above the ninetieth percentile of the control samples and MBF response below the sixtieth percentile for the control range, the NRA predicted SZ with 31% sensitivity and 97% specificity. Moreover, the NRA was not influenced by age, gender, race, and cigarette smoking. In summary, the NRA may define a SZ subtype with a clinically significant phospholipid signaling defect. Understanding its molecular origins may shed light on the pathophysiology of SZ and suggest new tools for its early diagnosis and treatment. Oxford University Press 2016-03 2015-09-14 /pmc/articles/PMC4753599/ /pubmed/26371338 http://dx.doi.org/10.1093/schbul/sbv130 Text en © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. http://creativecommons.org/licenses/by-nc-nd/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Regular Article
Yao, Jeffrey K.
Dougherty, George G.
Gautier, Clara H.
Haas, Gretchen L.
Condray, Ruth
Kasckow, John W.
Kisslinger, Benjamin L.
Gurklis, John A.
Messamore, Erik
Prevalence and Specificity of the Abnormal Niacin Response: A Potential Endophenotype Marker in Schizophrenia
title Prevalence and Specificity of the Abnormal Niacin Response: A Potential Endophenotype Marker in Schizophrenia
title_full Prevalence and Specificity of the Abnormal Niacin Response: A Potential Endophenotype Marker in Schizophrenia
title_fullStr Prevalence and Specificity of the Abnormal Niacin Response: A Potential Endophenotype Marker in Schizophrenia
title_full_unstemmed Prevalence and Specificity of the Abnormal Niacin Response: A Potential Endophenotype Marker in Schizophrenia
title_short Prevalence and Specificity of the Abnormal Niacin Response: A Potential Endophenotype Marker in Schizophrenia
title_sort prevalence and specificity of the abnormal niacin response: a potential endophenotype marker in schizophrenia
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4753599/
https://www.ncbi.nlm.nih.gov/pubmed/26371338
http://dx.doi.org/10.1093/schbul/sbv130
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