TY - JOUR
T1 - Examining the association between genetic liability for schizophrenia and psychotic symptoms in Alzheimer's disease
AU - AddNeuroMed consortium and the Alzheimer’s Disease Neuroimaging Initiative
AU - Creese, Byron
AU - Vassos, Evangelos
AU - Bergh, Sverre
AU - Athanasiu, Lavinia
AU - Johar, Iskandar
AU - Rongve, Arvid
AU - Medbøen, Ingrid Tøndel
AU - Vasconcelos Da Silva, Miguel
AU - Aakhus, Eivind
AU - Andersen, Fred
AU - Bettella, Francesco
AU - Braekhus, Anne
AU - Djurovic, Srdjan
AU - Paroni, Giulia
AU - Proitsi, Petroula
AU - Saltvedt, Ingvild
AU - Seripa, Davide
AU - Stordal, Eystein
AU - Fladby, Tormod
AU - Aarsland, Dag
AU - Andreassen, Ole A.
AU - Ballard, Clive
AU - Selbaek, Geir
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85073759054&partnerID=8YFLogxK
U2 - 10.1038/s41398-019-0592-5
DO - 10.1038/s41398-019-0592-5
M3 - Article
C2 - 31641104
AN - SCOPUS:85073759054
SN - 2158-3188
VL - 9
JO - Translational psychiatry
JF - Translational psychiatry
IS - 1
M1 - 273
ER -
