期刊
TRANSLATIONAL PSYCHIATRY
卷 9, 期 -, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41398-019-0592-5
关键词
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类别
资金
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense) [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- BioClinica, Inc.
- Biogen
- BristolMyers Squibb Company
- CereSpir, Inc.
- Cogstate
- Eisai Inc.
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- EuroImmun
- F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.
- Fujirebio
- GE Healthcare
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC.
- Johnson & Johnson Pharmaceutical Research & Development LLC.
- Lumosity
- Lundbeck
- Merck Co., Inc.
- Meso Scale Diagnostics, LLC.
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Servier
- Takeda Pharmaceutical Company
- Transition Therapeutics
- Canadian Institutes of Health Research
- National Institute on Aging [U24-AG041689]
- Alzheimer's Disease Genetics Consortium (ADGC) through National Institute on Aging (NIA) [U01AG032984, RC2AG036528]
- National Institute on Aging (NIA) [U24 AG21886]
- NIA/NIH [U01 AG016976]
- NIA [P30 AG019610, P30 AG013846, P50 AG008702, P50 AG025688, P50 AG047266, P30 AG010133, P50 AG005146, P50 AG005134, P50 AG016574, P50 AG005138, P30 AG008051, P30 AG013854, P30 AG008017, P30 AG010161, P50 AG047366, P30 AG010129]
- National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London
- Ministero della Salute, I.R.C.C.S. Research Program, Ricerca Corrente 2018-2020, Linea n. 2 Meccanismi genetici, predizione e terapie innovative delle malattie complesse
- 5 x 1000 voluntary
- EU FP6 program, InnoMed
- Alzheimer's Research UK
- South-Eastern Norway Regional Health Authority
- Norwegian National Advisory Unit on Ageing and Health
- Norwegian Institute of Public Health
- Norwegian University of Science and Technology (NTNU)
- Nord-Trondelag Hospital Trust
- Innlandet Hospital Trust
- Norwegian Health Directorate
- research centre for Age-Related Functional Decline and Disease, Innlandet Hospital Trust
- University of Exeter
- [P50 AG016573]
- [P50 AG016570]
- [P50 AG005131]
- [P50 AG023501]
- [P30 AG035982]
- [P30 AG028383]
- [P30 AG010124]
- [P50 AG005133]
- [P50 AG005142]
- [P30 AG012300]
- [P50 AG005136]
- [P50 AG033514]
- [P50 AG005681]
- [P50 AG047270]
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 (P-T) 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 P-T 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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