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Prediction of psychosis onset in Alzheimer disease: The role of depression symptom severity and the HTR2A T102C polymorphism
Author(s) -
Wilkosz Patricia A.,
Kodavali Chowdari,
Weamer Elise A.,
Miyahara Sachiko,
Lopez Oscar L.,
Nimgaonkar Vishwajit L.,
DeKosky Steven T.,
Sweet Robert A.
Publication year - 2007
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.30549
Subject(s) - psychosis , depression (economics) , psychology , age of onset , hazard ratio , medicine , proportional hazards model , genotype , psychiatry , disease , confidence interval , genetics , biology , gene , economics , macroeconomics
Psychotic symptoms in Alzheimer disease (AD + P) identify a heritable phenotype associated with a more severe course. We recently found an association of AD + P with depression symptom severity. Reports have shown an association of a serotonin‐2A receptor (HTR2A) gene T102C polymorphism with AD + P and with depression during AD. We examined the interaction of this common genetic polymorphism with depression and increased psychosis risk. Subjects with possible or probable AD or mild cognitive impairment (MCI) without psychosis at study entry were genotyped for the HTR2A T102C polymorphism and reassessed every 6 months until psychosis onset. Psychotic and depressive symptoms were rated using the CERAD behavioral rating scale (CBRS). Cox proportional hazard models with time‐dependent covariates were used to examine associations with psychosis onset. A total of 324 Caucasian subjects completed at least one follow‐up exam. Depressive symptom severity was a strong predictor of psychosis onset. Neither psychosis onset nor depression severity was associated with the HTR2A genotype. Genotype interacted with depression severity to moderate the risk of AD + P onset. This did not result from an interaction of HTR2A genotype with antidepressant use. Psychosis onset in AD is strongly associated with severity of depressive symptoms, an association that may be modified by HTR2A genotype. © 2007 Wiley‐Liss, Inc.