Page 61 - merged

S002-4

The Niacin Response Abnormality as a Potential Schizophrenia Endophenotype

Wei J. Chen

Institute of Epidemiology and Preventive Medicine College of Public Health National Taiwan University, Taiwan

Background/Objective: Among many potential schizophrenia-related quantitative traits, impaired
niacin flush response is one of the emerging candidate endophenotype for schizophrenia. We have
conducted a series of studies to evaluate the potential utility of this observation.

Method: First, we examined whether such a deficit may be a useful trait for quantitative trait loci
(QTL) genome-wide linkage scans for schizophrenia. Participants consisted of simplex families,
multiplex families, and 94 healthy controls. In the first 153 simplex families, there was substantial
familial aggregation in attenuated flush response and it remained after adjustment for potential
confounders. Comparing the simplex versus the multiplex families, more attenuated flush response
was shown in schizophrenia probands and their relatives from multiplex families than in their
counterparts from simplex families. On the basis of 115 multiplex families, linkage scan revealed a
linkage peak attaining genome-wide significance at 14q32.12 for 0.01M concentration at 5 minutes
(NPL-Z scores = 3.39, genome-wide empirical P = 0.03) in affected individuals. Second, we
examined whether attenuated niacin-induced flush response as well as fatty acids levels changed
from acute phase to partial remission phase. In this study, 46 schizophrenia inpatients were recruited
and were followed up for 2 months or until they were discharged from acute wards. Controls
consisted of 37 frequency-matched volunteers who had similar distribution in age and sex to
schizophrenia patients. The fatty acids of red blood cells for all participants were measured using gas
chromatography. Both at baseline and 2-month follow up, the mean flush scores of all concentration
and time points (except in 0.001 M, 5 min of baseline) were significantly lower in schizophrenia
group compared to control group.

Result: At admission, patients with schizophrenia had increased levels in -

Conclusion: In addition we will report higher levels of PSD 95 in caudate putamen from subjects
with schizophrenia which appeared more prominent in subjects with MRDS. Levels of SNAP 25 and
GFAP 41 and 43 were unchanged.