Dataset Information

Prediction of psychosis onset in Alzheimer disease: the role of depression symptom severity and the HTR2A T102C polymorphism.

ABSTRACT: 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.

SUBMITTER: Wilkosz PA

PROVIDER: S-EPMC2818007 | biostudies-literature | 2007 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Prediction of psychosis onset in Alzheimer disease: the role of depression symptom severity and the HTR2A T102C polymorphism.

Wilkosz Patricia A PA Kodavali Chowdari C Weamer Elise A EA Miyahara Sachiko S Lopez Oscar L OL Nimgaonkar Vishwajit L VL DeKosky Steven T ST Sweet Robert A RA

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 20071201 8

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 imp ...[more]

PMID: 17525976

Similar Datasets

Project description:ImportanceAlzheimer disease (AD) develops during several decades. Presymptomatic individuals might be the best candidates for clinical trials, but their identification is challenging because they have no symptoms.ObjectiveTo assess whether a sporadic parental estimated years to symptom onset calculation could be used to identify information about amyloid-? (A?) levels in asymptomatic individuals with a parental history of AD dementia.Design, setting, and participantsThis cohort study analyzed A?1-42 in cerebrospinal fluid (CSF) specimens from 101 cognitively normal individuals who had a lumbar puncture as part of the Presymptomatic Evaluation of Novel or Experimental Treatments for Alzheimer Disease (PREVENT-AD) cohort from September 1, 2011, through November 30, 2016 (374 participants were enrolled in the cohort during this period). The study estimated each participant's proximity to his/her parent's symptom onset by subtracting the index relative's onset age from his/her current age. The association between proximity to parental symptom onset and A? levels was then assessed using apolipoprotein E ?4 (APOE4) status and sex as interactive terms. These analyses were performed again in 2 independent cohorts using CSF and Pittsburgh compound B carbon 11-labeled positron emission tomography (PIB-PET) A? biomarkers: the Adult Children Study (ACS) and the Wisconsin Registry for Alzheimer Prevention (WRAP) cohorts.Main outcomes and measuresThe association between proximity to parental symptom onset and A? burden in asymptomatic individuals with a parental history of sporadic AD.ResultsThe present analysis included a subset of 101 PREVENT-AD individuals (mean [SD] age, 61.8 [5.1] years; 30 [29.7%] male), 128 ACS participants (112 participants underwent CSF measurement: mean [SD] age, 63.4 [5.1] years; 31 [27.7%] male; and 107 underwent PIB-PET: mean [SD] age, 64.6 [5.3] years; 27 [25.2%] male), and 135 WRAP participants (85 participants underwent CSF measurement: mean [SD] age, 59.9 [6.0] years; 27 [31.8%] male; and 135 underwent PIB-PET: mean [SD] age, 59.6 [6.1] years; 43 [31.9%] male). In the PREVENT-AD cohort, individuals approaching their parent's onset age had lower CSF A?1-42 levels (range, 402-1597; B?=?-9.09, P?=?.04). This association was stronger in APOE4 carriers (B?=?-17.9, P?=?.03) and women (B?=?-19.8, P?=?.02). In the ACS cohort, the main association was replicated using PIB-PET data, and the sex interaction was replicated using CSF and PIB-PET data. In the WRAP cohort, the results were not replicated using cross-sectional data, but the main association and the APOE interaction were replicated using PIB-PET longitudinal data.Conclusions and relevanceThese results suggest that proximity to parental symptom onset may help estimate A? biomarker changes in women or APOE4 carrier asymptomatic individuals with a parental history of sporadic AD.

Project description:BackgroundAn automated web-based assessment and monitoring system ( www.psynary.com ) has been developed to assist non-specialist clinicians in managing common mood and anxiety disorders. Psynary promotes the use of standardised outcome measures to assess symptom severity and optimise treatments with the aim of improving outcomes and enabling faster recovery. This paper analyses the results from two parallel studies in New Zealand and Japan (OptiMA-1 NZ and Japan) to assess the validity of the R8 Depression scale, one of the system's core outcome measures.MethodsClinical samples were recruited from a public secondary care and a private psychiatry clinic. Participants completed the outcome measures for the study via the online Psynary system. The R8 Depression scale is a 30-item questionnaire which includes all symptom domains covered in the ICD-10 classification of depression. The Patient Health Questionnaire (PHQ-9) was completed at the same time points as the R8 Depression, with a smaller sample also completing a paper-based Quick Inventory of Depressive Symptomatology (QIDS-SR16). Internal validity was quantified via Cronbach's alpha and Guttman lower bounds method. External validation against the PHQ-9 and QIDS used the Pearson's and Kendall's correlation coefficients. Severity categories were set using a multivariate regression model.Results270 patients participated in the study and completed a maximum of 1 baseline and 5 reviews within a 90-day period, giving a total of 1124 assessments with the PHQ-9 also being completed in 1053 of these assessments. R8 Depression normative data was also collected from 204 non-clinical volunteers with 187 of these also completing the PHQ9. Internal reliability scores were all higher than 0.9 (n = 1328). There was overall good external validity when comparing the R8 Depression to the PHQ-9, with a correlation of 0.91 for the combined normative and clinical samples (n = 1240).ConclusionsThe R8 Depression has been developed as a patient-rated outcome measure for depression for administration on an online system called "Psynary". It has high internal and external validity against current widely used scales. Further work is underway to determine the sensitivity to change of the R8 Depression.

Dataset Information

Prediction of psychosis onset in Alzheimer disease: the role of depression symptom severity and the HTR2A T102C polymorphism.

Publications

Prediction of psychosis onset in Alzheimer disease: the role of depression symptom severity and the HTR2A T102C polymorphism.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets