title: Prevalence and Specificity of the Abnormal Niacin Response: A Potential Endophenotype Marker in Schizophrenia.
abstract: 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 (EC50 value) and MBF value for each subject. The median log10EC50 of the SZ was above the third quartile of log10EC50 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 EC50 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.
authors.affiliation: jkyao@pitt.edu.
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Yao
authors.affiliation: Medical Research Service, VA Pittsburgh Healthcare System, Pittsburgh, PA; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA;
authors.forename: George G
authors.initials: GG
authors.lastname: Dougherty
authors.affiliation: Medical Research Service, VA Pittsburgh Healthcare System, Pittsburgh, PA;
authors.forename: Clara H
authors.initials: CH
authors.lastname: Gautier
authors.affiliation: Medical Research Service, VA Pittsburgh Healthcare System, Pittsburgh, PA; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA;
authors.forename: Gretchen L
authors.initials: GL
authors.lastname: Haas
authors.affiliation: Medical Research Service, VA Pittsburgh Healthcare System, Pittsburgh, PA;
authors.forename: Ruth
authors.initials: R
authors.lastname: Condray
authors.affiliation: Medical Research Service, VA Pittsburgh Healthcare System, Pittsburgh, PA; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA;
authors.forename: John W
authors.initials: JW
authors.lastname: Kasckow
authors.affiliation: Medical Research Service, VA Pittsburgh Healthcare System, Pittsburgh, PA;
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Kisslinger
authors.affiliation: Medical Research Service, VA Pittsburgh Healthcare System, Pittsburgh, PA;
authors.forename: John A
authors.initials: JA
authors.lastname: Gurklis
authors.affiliation: Department of Psychiatry, University of Cincinnati and Lindner Center for Hope, Cincinnati, OH.
authors.forename: Erik
authors.initials: E
authors.lastname: Messamore
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000378:metabolism*; D058068:Endophenotypes / Q000378:metabolism*; D005260:Female; D005483:Flushing; D006801:Humans; D017078:Laser-Doppler Flowmetry; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000493:pharmacokinetics / Q000494:pharmacology*; D015995:Prevalence; D011618:Psychotic Disorders / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism*; D012680:Sensitivity and Specificity; D014665:Vasodilator Agents / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D014665:Vasodilator Agents; D009525:Niacin
keywords: EC50; bipolar disorder; laser Doppler flowmeter; maximal blood flow; niacin-induced flush response; phospholipid-arachidonate-eicosanoid signaling