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

Byron Creese; Evangelos Vassos; Sverre Bergh; Lavinia Athanasiu; Iskandar Johar; Arvid Rongve; Ingrid Tøndel Medbøen; Miguel Vasconcelos Da Silva; Eivind Aakhus; Fred Andersen; Francesco Bettella; Anne Braekhus; Srdjan Djurovic; Giulia Paroni; Petroula Proitsi; Ingvild Saltvedt; Davide Seripa; Eystein Stordal; Tormod Fladby; Dag Aarsland; Ole A Andreassen; Clive Ballard; Geir Selbaek; AddNeuroMed consortium and the Alzheimer’s Disease Neuroimaging Initiative

doi:10.1038/s41398-019-0592-5

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

Transl Psychiatry. 2019 Oct 22;9(1):273. doi: 10.1038/s41398-019-0592-5.

Authors

Byron Creese^{1

2}, Evangelos Vassos³, Sverre Bergh^{4

5

6}, Lavinia Athanasiu^{7

8}, Iskandar Johar^{4

9}, Arvid Rongve^{4

10

11}, Ingrid Tøndel Medbøen^{6

12}, Miguel Vasconcelos Da Silva^{13

4

9}, Eivind Aakhus⁵, Fred Andersen¹⁴, Francesco Bettella^{7

8}, Anne Braekhus^{6

12

15}, Srdjan Djurovic^{11

16

17}, Giulia Paroni¹⁸, Petroula Proitsi¹⁹, Ingvild Saltvedt^{20

21}, Davide Seripa¹⁸, Eystein Stordal^{22

23}, Tormod Fladby^{24

25}, Dag Aarsland^{4

9

26}, Ole A Andreassen^{7

8}, Clive Ballard^{13

4}, Geir Selbaek^{4

5

6

27}; AddNeuroMed consortium and the Alzheimer’s Disease Neuroimaging Initiative

Affiliations

¹ University of Exeter Medical School, Exeter, UK. b.creese@exeter.ac.uk.
² Norwegian, Exeter and King's College Consortium for Genetics of Neuropsychiatric Symptoms in Dementia, Exeter, UK. b.creese@exeter.ac.uk.
³ Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁴ Norwegian, Exeter and King's College Consortium for Genetics of Neuropsychiatric Symptoms in Dementia, Exeter, UK.
⁵ Research Centre of Age-Related Functional Decline and Disease, Innlandet Hospital Trust, Pb 68, 2312, Ottestad, Norway.
⁶ Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway.
⁷ NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁸ NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
⁹ Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
¹⁰ Department of Research and Innovation, Helse Fonna, Haugesund, Norway.
¹¹ Department of Clinical Medicine, University of Bergen, Bergen, Norway.
¹² Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway.
¹³ University of Exeter Medical School, Exeter, UK.
¹⁴ Department of Community Medicine, University of Tromsø, Tromsø, Norway.
¹⁵ Department of Neurology, Oslo University Hospital, Oslo, Norway.
¹⁶ NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway.
¹⁷ Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
¹⁸ Complex Structure of Geriatrics, Department of Medical Sciences, Fondazione IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
¹⁹ Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
²⁰ Geriatric Department, St. Olav Hospital, University Hospital of Trondheim, Trondheim, Norway.
²¹ Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.
²² Department of Mental Health, Norwegian University of Science and Technology, Trondheim, Norway.
²³ Department of Psychiatry, Namsos Hospital, Namsos, Norway.
²⁴ Department of Neurology, Akershus University Hospital, Lørenskog, Norway.
²⁵ Institute of Clinical Medicine, Campus Ahus, University of Oslo, Oslo, Norway.
²⁶ Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
²⁷ Faculty of Medicine, University of Oslo, Oslo, Norway.

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 (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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease / complications*
Alzheimer Disease / genetics
Cohort Studies
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Logistic Models
Male
Multifactorial Inheritance*
Polymorphism, Single Nucleotide
Psychotic Disorders / complications
Psychotic Disorders / diagnosis*
Psychotic Disorders / genetics*
Risk Assessment
Risk Factors
Schizophrenia / complications*
Schizophrenia / genetics

Abstract

Publication types

MeSH terms

Grants and funding