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NOTCH4 and the frontal lobe in schizophrenia
Author(s) -
Wassink Thomas H.,
Nopoulos Peggy,
Pietila Jennifer,
Crowe Raymond R.,
Andreasen Nancy C.
Publication year - 2003
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.10071
Subject(s) - frontal lobe , schizophrenia (object oriented programming) , cognition , phenotype , neuroscience , psychosis , psychology , linkage disequilibrium , temporal lobe , trait , association (psychology) , allele , imaging genetics , biology , genetics , neuroimaging , psychiatry , gene , haplotype , computer science , epilepsy , psychotherapist , programming language
NOTCH4 is a developmentally expressed gene recently reported to be in linkage disequilibrium (LD) with schizophrenia. We investigated this finding in our sample of subjects, focusing on an exonic (CTG) n polymorphism, examining not only the association of this polymorphism with the disease phenotype, but also its effect on frontal lobe brain morphology and cognitive function in both affected individuals and a psychiatrically normal comparison group. While we did not find any association or LD with schizophrenia, we identified striking effects of NOTCH4 variability on the trait measures. Within the respective schizophrenia and comparison groups, NOTCH4 allelic variability was correlated with differences in measures of frontal lobe cognitive performance and frontal lobe brain tissue volumes that were intuitively congruent. These within‐group effects, however, were in opposite directions across groups. These findings may reflect the interaction of NOTCH4 with the underlying genetic and phenotypic complexity that characterizes both schizophrenia and normal cognition and brain development. © 2003 Wiley‐Liss, Inc.