Examining the association between genetic liability for schizophrenia and psychotic symptoms in Alzheimer's disease

AddNeuroMed consortium and the Alzheimer’s Disease Neuroimaging Initiative

Research output: Contribution to journalArticle

Abstract

Psychosis (delusions or hallucinations) in Alzheimer's disease (AD + P) occurs in up to 50% of individuals and is associated with significantly worse clinical outcomes. Atypical antipsychotics, first developed for schizophrenia, are commonly used in AD + P, suggesting shared mechanisms. Despite this implication, little empirical research has been conducted to examine whether there are mechanistic similarities between AD + P and schizophrenia. In this study, we tested whether polygenic risk score (PRS) for schizophrenia was associated with AD + P. Schizophrenia PRS was calculated using Psychiatric Genomics Consortium data at ten GWAS p value thresholds (PT) in 3111 AD cases from 11 cohort studies characterized for psychosis using validated, standardized tools. Association between PRS and AD + P status was tested by logistic regression in each cohort individually and the results meta-analyzed. The schizophrenia PRS was associated with AD + P at an optimum PT of 0.01. The strongest association was for delusions where a one standard deviation increase in PRS was associated with a 1.18-fold increased risk (95% CI: 1.06-1.3; p = 0.001). These new findings point towards psychosis in AD-and particularly delusions-sharing some genetic liability with schizophrenia and support a transdiagnostic view of psychotic symptoms across the lifespan.

Original languageEnglish
Number of pages1
JournalTranslational Psychiatry
Volume9
Issue number1
DOIs
Publication statusPublished - Oct 22 2019

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Schizophrenia
Alzheimer Disease
Delusions
Psychotic Disorders
Empirical Research
Genome-Wide Association Study
Hallucinations
Genomics
Antipsychotic Agents
Psychiatry
Cohort Studies
Logistic Models

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

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Examining the association between genetic liability for schizophrenia and psychotic symptoms in Alzheimer's disease. / AddNeuroMed consortium and the Alzheimer’s Disease Neuroimaging Initiative.

In: Translational Psychiatry, Vol. 9, No. 1, 22.10.2019.

Research output: Contribution to journalArticle

AddNeuroMed consortium and the Alzheimer’s Disease Neuroimaging Initiative. / Examining the association between genetic liability for schizophrenia and psychotic symptoms in Alzheimer's disease. In: Translational Psychiatry. 2019 ; Vol. 9, No. 1.
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abstract = "Psychosis (delusions or hallucinations) in Alzheimer's disease (AD + P) occurs in up to 50{\%} of individuals and is associated with significantly worse clinical outcomes. Atypical antipsychotics, first developed for schizophrenia, are commonly used in AD + P, suggesting shared mechanisms. Despite this implication, little empirical research has been conducted to examine whether there are mechanistic similarities between AD + P and schizophrenia. In this study, we tested whether polygenic risk score (PRS) for schizophrenia was associated with AD + P. Schizophrenia PRS was calculated using Psychiatric Genomics Consortium data at ten GWAS p value thresholds (PT) in 3111 AD cases from 11 cohort studies characterized for psychosis using validated, standardized tools. Association between PRS and AD + P status was tested by logistic regression in each cohort individually and the results meta-analyzed. The schizophrenia PRS was associated with AD + P at an optimum PT of 0.01. The strongest association was for delusions where a one standard deviation increase in PRS was associated with a 1.18-fold increased risk (95{\%} CI: 1.06-1.3; p = 0.001). These new findings point towards psychosis in AD-and particularly delusions-sharing some genetic liability with schizophrenia and support a transdiagnostic view of psychotic symptoms across the lifespan.",
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