The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study
Diego Quattrone
(1, 2, 3)
,
Ulrich Reininghaus
(1, 4, 3)
,
Alex L Richards
(5, 6)
,
Giada Tripoli
(7)
,
Laura Ferraro
(7)
,
Andrea Quattrone
(8)
,
Paolo Marino
(1)
,
Victoria Rodriguez
(1)
,
Edoardo Spinazzola
(1)
,
Charlotte Gayer-Anderson
(1)
,
Hannah E Jongsma
(9, 10)
,
Peter B Jones
(11, 12)
,
Caterina La Cascia
(8)
,
Daniele La Barbera
(8)
,
Ilaria Tarricone
(13)
,
Elena Bonora
(13)
,
Sarah Tosato
(14)
,
Antonio Lasalvia
(14)
,
Andrei Szöke
(15)
,
Celso Arango
(16, 17, 18, 19)
,
Miquel Bernardo
(20, 21, 22, 18)
,
Julio Bobes
(23, 18, 23)
,
Cristina Marta del Ben
(24)
,
Paulo Rossi Menezes
(24)
,
Pierre-Michel Llorca
(25, 26, 27)
,
Jose Luis Santos
(28)
,
Julio Sanjuán
(18, 29)
,
Manuel Arrojo
(30)
,
Andrea Tortelli
(31)
,
Eva Velthorst
(32, 33)
,
Steven Berendsen
(33)
,
Lieuwe de Haan
(33)
,
Bart P F Rutten
(4)
,
Michael T Lynskey
(1)
,
Tom P Freeman
(1, 34)
,
James B Kirkbride
(9)
,
Pak C Sham
(35, 36)
,
Michael C O’donovan
(6, 5)
,
Alastair G Cardno
(37, 38)
,
Evangelos Vassos
(1, 2)
,
Jim van Os
(4, 39)
,
Craig Morgan
(1)
,
Robin M Murray
(7, 2)
,
Cathryn M Lewis
(1, 2)
,
Marta Di Forti
(1, 2)
1
Institute of Psychiatry, Psychology & Neuroscience, King's College London
2 SLAM - South London and Maudsley NHS Mental Health Foundation Trust
3 University of Heidelberg, Medical Faculty
4 MUMC - Maastricht University Medical Centre
5 MRC Centre for Neuropsychiatric Genetics and Genomics
6 Cardiff University
7 Università degli studi di Palermo - University of Palermo
8 VBPI - Villa Betania Psychological Institute [Reggio Calabria, Italy]
9 UCL - University College of London [London]
10 UMCG - University Medical Center Groningen [Groningen]
11 CAM - University of Cambridge [UK]
12 CPFT - Cambridgeshire & Peterborough NHS Foundation Trust [Cambridge]
13 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
14 UNIVR - Università degli studi di Verona = University of Verona
15 U955 Inserm - UPEC - IMRB - "Neuropsychiatrie translationnelle" [Créteil]
16 UCM - Universidad Complutense de Madrid = Complutense University of Madrid [Madrid]
17 IiSGM - Instituto de Investigación Sanitaria Gregorio Marañón / Institute of Health Research Gregorio Marañón [Madrid, Spain]
18 CIBER-SAM - Centro de Investigación Biomédica en Red Salud Mental [Madrid]
19 Hospital General Universitario "Gregorio Marañón" [Madrid]
20 Clinic Barcelona Hospital Universitari
21 University of Barcelona
22 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
23 Universidad de Oviedo = University of Oviedo
24 USP - Universidade de São Paulo = University of São Paulo
25 IP - Institut Pascal
26 UCA - Université Clermont Auvergne
27 INP Clermont Auvergne - Institut national polytechnique Clermont Auvergne
28 HVDL - Hospital Virgen de La Luz [Cuenca, Spain]
29 UCV - Universidad Catolica de Valencia San Vicente Mártir = Saint Vincent the Martyr Catholic University of Valencia
30 CHUS - Complejo Hospitalario Universitario de Santiago de Compostela [Saint-Jacques-de-Compostelle, Espagne]
31 EPSMB - Établissement Public de Santé Maison Blanche [Paris]
32 MSSM - Icahn School of Medicine at Mount Sinai [New York]
33 UvA - University of Amsterdam [Amsterdam] = Universiteit van Amsterdam
34 University of Bath [Bath]
35 HKU - The University of Hong Kong
36 Li Kashing Faculty of Medicine [Hong Kong]
37 Leeds Institute of Health Sciences
38 University of Leeds
39 UMCU - University Medical Center [Utrecht]
2 SLAM - South London and Maudsley NHS Mental Health Foundation Trust
3 University of Heidelberg, Medical Faculty
4 MUMC - Maastricht University Medical Centre
5 MRC Centre for Neuropsychiatric Genetics and Genomics
6 Cardiff University
7 Università degli studi di Palermo - University of Palermo
8 VBPI - Villa Betania Psychological Institute [Reggio Calabria, Italy]
9 UCL - University College of London [London]
10 UMCG - University Medical Center Groningen [Groningen]
11 CAM - University of Cambridge [UK]
12 CPFT - Cambridgeshire & Peterborough NHS Foundation Trust [Cambridge]
13 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
14 UNIVR - Università degli studi di Verona = University of Verona
15 U955 Inserm - UPEC - IMRB - "Neuropsychiatrie translationnelle" [Créteil]
16 UCM - Universidad Complutense de Madrid = Complutense University of Madrid [Madrid]
17 IiSGM - Instituto de Investigación Sanitaria Gregorio Marañón / Institute of Health Research Gregorio Marañón [Madrid, Spain]
18 CIBER-SAM - Centro de Investigación Biomédica en Red Salud Mental [Madrid]
19 Hospital General Universitario "Gregorio Marañón" [Madrid]
20 Clinic Barcelona Hospital Universitari
21 University of Barcelona
22 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
23 Universidad de Oviedo = University of Oviedo
24 USP - Universidade de São Paulo = University of São Paulo
25 IP - Institut Pascal
26 UCA - Université Clermont Auvergne
27 INP Clermont Auvergne - Institut national polytechnique Clermont Auvergne
28 HVDL - Hospital Virgen de La Luz [Cuenca, Spain]
29 UCV - Universidad Catolica de Valencia San Vicente Mártir = Saint Vincent the Martyr Catholic University of Valencia
30 CHUS - Complejo Hospitalario Universitario de Santiago de Compostela [Saint-Jacques-de-Compostelle, Espagne]
31 EPSMB - Établissement Public de Santé Maison Blanche [Paris]
32 MSSM - Icahn School of Medicine at Mount Sinai [New York]
33 UvA - University of Amsterdam [Amsterdam] = Universiteit van Amsterdam
34 University of Bath [Bath]
35 HKU - The University of Hong Kong
36 Li Kashing Faculty of Medicine [Hong Kong]
37 Leeds Institute of Health Sciences
38 University of Leeds
39 UMCU - University Medical Center [Utrecht]
Alex L Richards
- Fonction : Auteur
- PersonId : 1280881
- ORCID : 0000-0003-3218-7247
Paolo Marino
- Fonction : Auteur
- PersonId : 1280949
- ORCID : 0000-0003-3571-1753
Victoria Rodriguez
- Fonction : Auteur
- PersonId : 1280932
- ORCID : 0000-0003-0383-0846
Peter B Jones
- Fonction : Auteur
- PersonId : 1280950
- ORCID : 0000-0002-0387-880X
Sarah Tosato
- Fonction : Auteur
- PersonId : 1280938
- ORCID : 0000-0002-9665-7538
Celso Arango
- Fonction : Auteur
Julio Bobes
- Fonction : Auteur
- PersonId : 1248968
- ORCID : 0000-0003-2187-4033
Cristina Marta del Ben
- Fonction : Auteur
- PersonId : 1280952
- ORCID : 0000-0003-0145-9975
Paulo Rossi Menezes
- Fonction : Auteur
- PersonId : 1280953
- ORCID : 0000-0001-6330-3314
Pierre-Michel Llorca
- Fonction : Auteur
- PersonId : 781416
- ORCID : 0000-0001-7438-8990
- IdRef : 05967797X
Bart P F Rutten
- Fonction : Auteur
- PersonId : 1280954
- ORCID : 0000-0002-9834-6346
James B Kirkbride
- Fonction : Auteur
- PersonId : 1280879
- ORCID : 0000-0003-3401-0824
Michael C O’donovan
- Fonction : Auteur
- PersonId : 1280955
- ORCID : 0000-0001-7073-2379
Evangelos Vassos
- Fonction : Auteur
- PersonId : 1280956
- ORCID : 0000-0001-6363-0438
Robin M Murray
- Fonction : Auteur
- PersonId : 1280957
- ORCID : 0000-0003-0829-0519
Cathryn M Lewis
- Fonction : Auteur
- PersonId : 1215664
- ORCID : 0000-0002-8249-8476
Résumé
Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03-0.33) and positive (B = 0.19; 95%CI 0.03-0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and the general and affective dimensions in FEP. Daily and current cannabis use were associated with the positive dimensions in FEP (B = 0.31; 95%CI 0.11-0.52) and in controls (B = 0.26; 95%CI 0.06-0.46), over and above SZ-PRS. We provide evidence that genetic liability to schizophrenia and cannabis use map onto transdiagnostic symptom dimensions, supporting the validity and utility of the dimensional representation of psychosis. In our sample, genetic liability to schizophrenia correlated with more severe psychosis presentation, and cannabis use conferred risk to positive symptomatology beyond the genetic risk. Our findings support the hypothesis that psychotic experiences in the general population have similar genetic substrates as clinical disorders.
Domaines
Sciences du Vivant [q-bio]| Origine | Publication financée par une institution |
|---|---|
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