Independent contribution of polygenic risk for schizophrenia and cannabis use in predicting psychotic-like experiences in young adulthood: Testing gene × environment moderation and mediation

Laurent Elkrief; Bochao Lin; Mattia Marchi; Mohammad H. Afzali; Tobias Banaschewski; Arun L.W. Bokde; Erin Burke Quinlan; Sylvane Desrivières; Herta Flor; Hugh Garavan; Penny Gowland; Andreas Heinz; Bernd Ittermann; Jean Luc Martinot; Marie Laure Paillère Martinot; Frauke Nees; Dimitri Papadopoulos Orfanos; Tomáš Paus; Luise Poustka; Sarah Hohmann; Juliane H. Fröhner; Michael N. Smolka; Henrik Walter; Robert Whelan; Gunter Schumann; Jurjen Luykx; Marco P. Boks; Patricia J. Conrod

doi:10.1017/S0033291721003378

Independent contribution of polygenic risk for schizophrenia and cannabis use in predicting psychotic-like experiences in young adulthood: Testing gene × environment moderation and mediation

Laurent Elkrief^*, Bochao Lin, Mattia Marchi, Mohammad H. Afzali, Tobias Banaschewski, Arun L.W. Bokde, Erin Burke Quinlan, Sylvane Desrivières, Herta Flor, Hugh Garavan, Penny Gowland, Andreas Heinz, Bernd Ittermann, Jean Luc Martinot, Marie Laure Paillère Martinot, Frauke Nees, Dimitri Papadopoulos Orfanos, Tomáš Paus, Luise Poustka, Sarah HohmannJuliane H. Fröhner, Michael N. Smolka, Henrik Walter, Robert Whelan, Gunter Schumann, Jurjen Luykx, Marco P. Boks, Patricia J. Conrod

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

Abstract

Background It has not yet been determined if the commonly reported cannabis-psychosis association is limited to individuals with pre-existing genetic risk for psychotic disorders. Methods We examined whether the relationship between polygenic risk score for schizophrenia (PRS-Sz) and psychotic-like experiences (PLEs), as measured by the Community Assessment of Psychic Experiences-42 (CAPE-42) questionnaire, is mediated or moderated by lifetime cannabis use at 16 years of age in 1740 of the individuals of the European IMAGEN cohort. Secondary analysis examined the relationships between lifetime cannabis use, PRS-Sz and the various sub-scales of the CAPE-42. Sensitivity analyses including covariates, including a PRS for cannabis use, were conducted and results were replicated using data from 1223 individuals in the Dutch Utrecht cannabis cohort. Results PRS-Sz significantly predicted cannabis use (p = 0.027) and PLE (p = 0.004) in the IMAGEN cohort. In the full model, considering PRS-Sz and covariates, cannabis use was also significantly associated with PLE in IMAGEN (p = 0.007). Results remained consistent in the Utrecht cohort and through sensitivity analyses. Nevertheless, there was no evidence of a mediation or moderation effects. Conclusions These results suggest that cannabis use remains a risk factor for PLEs, over and above genetic vulnerability for schizophrenia. This research does not support the notion that the cannabis-psychosis link is limited to individuals who are genetically predisposed to psychosis and suggests a need for research focusing on cannabis-related processes in psychosis that cannot be explained by genetic vulnerability.

Original language	English
Pages (from-to)	1-11
Number of pages	11
Journal	Psychological Medicine
DOIs	https://doi.org/10.1017/S0033291721003378
Publication status	Accepted/In press - 2021

Keywords

cannabis
Polygenic risk score
psychosis risk
psychotic-like experience

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1017/S0033291721003378

Cite this

Elkrief, L., Lin, B., Marchi, M., Afzali, M. H., Banaschewski, T., Bokde, A. L. W., Quinlan, E. B., Desrivières, S., Flor, H., Garavan, H., Gowland, P., Heinz, A., Ittermann, B., Martinot, J. L., Martinot, M. L. P., Nees, F., Orfanos, D. P., Paus, T., Poustka, L., ... Conrod, P. J. (Accepted/In press). Independent contribution of polygenic risk for schizophrenia and cannabis use in predicting psychotic-like experiences in young adulthood: Testing gene × environment moderation and mediation. Psychological Medicine, 1-11. https://doi.org/10.1017/S0033291721003378

@article{313420cc6b7547fb90fcf768745a34eb,

title = "Independent contribution of polygenic risk for schizophrenia and cannabis use in predicting psychotic-like experiences in young adulthood: Testing gene × environment moderation and mediation",

abstract = "Background It has not yet been determined if the commonly reported cannabis-psychosis association is limited to individuals with pre-existing genetic risk for psychotic disorders. Methods We examined whether the relationship between polygenic risk score for schizophrenia (PRS-Sz) and psychotic-like experiences (PLEs), as measured by the Community Assessment of Psychic Experiences-42 (CAPE-42) questionnaire, is mediated or moderated by lifetime cannabis use at 16 years of age in 1740 of the individuals of the European IMAGEN cohort. Secondary analysis examined the relationships between lifetime cannabis use, PRS-Sz and the various sub-scales of the CAPE-42. Sensitivity analyses including covariates, including a PRS for cannabis use, were conducted and results were replicated using data from 1223 individuals in the Dutch Utrecht cannabis cohort. Results PRS-Sz significantly predicted cannabis use (p = 0.027) and PLE (p = 0.004) in the IMAGEN cohort. In the full model, considering PRS-Sz and covariates, cannabis use was also significantly associated with PLE in IMAGEN (p = 0.007). Results remained consistent in the Utrecht cohort and through sensitivity analyses. Nevertheless, there was no evidence of a mediation or moderation effects. Conclusions These results suggest that cannabis use remains a risk factor for PLEs, over and above genetic vulnerability for schizophrenia. This research does not support the notion that the cannabis-psychosis link is limited to individuals who are genetically predisposed to psychosis and suggests a need for research focusing on cannabis-related processes in psychosis that cannot be explained by genetic vulnerability.",

keywords = "cannabis, Polygenic risk score, psychosis risk, psychotic-like experience",

author = "Laurent Elkrief and Bochao Lin and Mattia Marchi and Afzali, {Mohammad H.} and Tobias Banaschewski and Bokde, {Arun L.W.} and Quinlan, {Erin Burke} and Sylvane Desrivi{\`e}res and Herta Flor and Hugh Garavan and Penny Gowland and Andreas Heinz and Bernd Ittermann and Martinot, {Jean Luc} and Martinot, {Marie Laure Paill{\`e}re} and Frauke Nees and Orfanos, {Dimitri Papadopoulos} and Tom{\'a}{\v s} Paus and Luise Poustka and Sarah Hohmann and Fr{\"o}hner, {Juliane H.} and Smolka, {Michael N.} and Henrik Walter and Robert Whelan and Gunter Schumann and Jurjen Luykx and Boks, {Marco P.} and Conrod, {Patricia J.}",

note = "Funding Information: Dr Conrod is supported by a Tier 1 Canada Research Chair and this research was supported by a CIHR catalyst grant FRN155406 and the Canadian Cannabis and Psychosis Research Team Grant (CIHR FRN CA7170130) and National Institute on Drug Abuse, Grant/Award Numbeer: 1R01DA047119-01. This study received support from the following sources: the European Union-funded FP6 Integrated Project IMAGEN (Reinforcement-related behaviour in normal brain function and psychopathology) (LSHM-CT- 2007-037286), the Horizon 2020 funded ERC Advanced Grant {\textquoteleft}STRATIFY{\textquoteright} (Brain network-based stratification of reinforcement-related disorders) (695313), ERANID (Understanding the Interplay between Cultural, Biological and Subjective Factors in Drug Use Pathways) (PR-ST-0416-10004), BRIDGET (JPND: BRain Imaging, cognition Dementia and next generation GEnomics) (MR/N027558/1), Human Brain Project (HBP SGA 2, 785907), the FP7 project MATRICS (603016), the Medical Research Council Grant {\textquoteleft}c-VEDA{\textquoteright} (Consortium on Vulnerability to Externalising Disorders and Addictions) (MR/N000390/1), the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, the Bundesministeriumf{\"u}r Bildung und Forschung (BMBF grants 01GS08152; 01EV0711; Forschungsnetz AERIAL 01EE1406A, 01EE1406B), the Deutsche Forschungsgemeinschaft (DFG grants SM 80/7-2, SFB 940/2), the Medical Research Foundation and Medical Research Council (grants MR/R00465X/1 and MR/S020306/1), the National Institutes of Health (NIH) funded ENIGMA (grants 5U54EB020403-05 and 1R56AG058854-01). Further support was provided by grants from: ANR (project AF12-NEUR0008-01 – WM2NA and ANR-12-SAMA-0004), the Eranet Neuron (ANR-18-NEUR00002-01), the Fondation de France (00081242), the Fondation pour la Recherche M{\'e}dicale (DPA20140629802), the Mission Interminist{\'e}rielle de Lutte-contre-les-Drogues-et-les-Conduites-Addictives (MILDECA), the Assistance-Publique-H{\^o}pitaux-de-Paris and INSERM (interface grant), Paris Sud University IDEX 2012, the fondation de l'Avenir (grant AP-RM-17-013); the National Institutes of Health, Science Foundation Ireland (16/ERCD/3797), USA (Axon, Testosterone and Mental Health during Adolescence; RO1 MH085772-01A1) and by NIH Consortium grant U54 EB020403, supported by a cross-NIH alliance that funds Big Data to Knowledge Centres of Excellence. Funding for the Utrecht cannabis cohort was provided by NWO, the Dutch council for scientific research (ZonMW TOP grant no. 91207039). Publisher Copyright: {\textcopyright} The Author(s), 2021. Published by Cambridge University Press. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

doi = "10.1017/S0033291721003378",

language = "English",

pages = "1--11",

journal = "Psychological Medicine",

issn = "0033-2917",

publisher = "Cambridge University Press",

}

Elkrief, L, Lin, B, Marchi, M, Afzali, MH, Banaschewski, T, Bokde, ALW, Quinlan, EB , Desrivières, S, Flor, H, Garavan, H, Gowland, P, Heinz, A, Ittermann, B, Martinot, JL, Martinot, MLP, Nees, F, Orfanos, DP, Paus, T, Poustka, L, Hohmann, S, Fröhner, JH, Smolka, MN, Walter, H, Whelan, R, Schumann, G, Luykx, J, Boks, MP & Conrod, PJ 2021, 'Independent contribution of polygenic risk for schizophrenia and cannabis use in predicting psychotic-like experiences in young adulthood: Testing gene × environment moderation and mediation', Psychological Medicine, pp. 1-11. https://doi.org/10.1017/S0033291721003378

TY - JOUR

T1 - Independent contribution of polygenic risk for schizophrenia and cannabis use in predicting psychotic-like experiences in young adulthood

T2 - Testing gene × environment moderation and mediation

AU - Elkrief, Laurent

AU - Lin, Bochao

AU - Marchi, Mattia

AU - Afzali, Mohammad H.

AU - Banaschewski, Tobias

AU - Bokde, Arun L.W.

AU - Quinlan, Erin Burke

AU - Desrivières, Sylvane

AU - Flor, Herta

AU - Garavan, Hugh

AU - Gowland, Penny

AU - Heinz, Andreas

AU - Ittermann, Bernd

AU - Martinot, Jean Luc

AU - Martinot, Marie Laure Paillère

AU - Nees, Frauke

AU - Orfanos, Dimitri Papadopoulos

AU - Paus, Tomáš

AU - Poustka, Luise

AU - Hohmann, Sarah

AU - Fröhner, Juliane H.

AU - Smolka, Michael N.

AU - Walter, Henrik

AU - Whelan, Robert

AU - Schumann, Gunter

AU - Luykx, Jurjen

AU - Boks, Marco P.

AU - Conrod, Patricia J.

N1 - Funding Information: Dr Conrod is supported by a Tier 1 Canada Research Chair and this research was supported by a CIHR catalyst grant FRN155406 and the Canadian Cannabis and Psychosis Research Team Grant (CIHR FRN CA7170130) and National Institute on Drug Abuse, Grant/Award Numbeer: 1R01DA047119-01. This study received support from the following sources: the European Union-funded FP6 Integrated Project IMAGEN (Reinforcement-related behaviour in normal brain function and psychopathology) (LSHM-CT- 2007-037286), the Horizon 2020 funded ERC Advanced Grant ‘STRATIFY’ (Brain network-based stratification of reinforcement-related disorders) (695313), ERANID (Understanding the Interplay between Cultural, Biological and Subjective Factors in Drug Use Pathways) (PR-ST-0416-10004), BRIDGET (JPND: BRain Imaging, cognition Dementia and next generation GEnomics) (MR/N027558/1), Human Brain Project (HBP SGA 2, 785907), the FP7 project MATRICS (603016), the Medical Research Council Grant ‘c-VEDA’ (Consortium on Vulnerability to Externalising Disorders and Addictions) (MR/N000390/1), the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, the Bundesministeriumfür Bildung und Forschung (BMBF grants 01GS08152; 01EV0711; Forschungsnetz AERIAL 01EE1406A, 01EE1406B), the Deutsche Forschungsgemeinschaft (DFG grants SM 80/7-2, SFB 940/2), the Medical Research Foundation and Medical Research Council (grants MR/R00465X/1 and MR/S020306/1), the National Institutes of Health (NIH) funded ENIGMA (grants 5U54EB020403-05 and 1R56AG058854-01). Further support was provided by grants from: ANR (project AF12-NEUR0008-01 – WM2NA and ANR-12-SAMA-0004), the Eranet Neuron (ANR-18-NEUR00002-01), the Fondation de France (00081242), the Fondation pour la Recherche Médicale (DPA20140629802), the Mission Interministérielle de Lutte-contre-les-Drogues-et-les-Conduites-Addictives (MILDECA), the Assistance-Publique-Hôpitaux-de-Paris and INSERM (interface grant), Paris Sud University IDEX 2012, the fondation de l'Avenir (grant AP-RM-17-013); the National Institutes of Health, Science Foundation Ireland (16/ERCD/3797), USA (Axon, Testosterone and Mental Health during Adolescence; RO1 MH085772-01A1) and by NIH Consortium grant U54 EB020403, supported by a cross-NIH alliance that funds Big Data to Knowledge Centres of Excellence. Funding for the Utrecht cannabis cohort was provided by NWO, the Dutch council for scientific research (ZonMW TOP grant no. 91207039). Publisher Copyright: © The Author(s), 2021. Published by Cambridge University Press. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021

Y1 - 2021

N2 - Background It has not yet been determined if the commonly reported cannabis-psychosis association is limited to individuals with pre-existing genetic risk for psychotic disorders. Methods We examined whether the relationship between polygenic risk score for schizophrenia (PRS-Sz) and psychotic-like experiences (PLEs), as measured by the Community Assessment of Psychic Experiences-42 (CAPE-42) questionnaire, is mediated or moderated by lifetime cannabis use at 16 years of age in 1740 of the individuals of the European IMAGEN cohort. Secondary analysis examined the relationships between lifetime cannabis use, PRS-Sz and the various sub-scales of the CAPE-42. Sensitivity analyses including covariates, including a PRS for cannabis use, were conducted and results were replicated using data from 1223 individuals in the Dutch Utrecht cannabis cohort. Results PRS-Sz significantly predicted cannabis use (p = 0.027) and PLE (p = 0.004) in the IMAGEN cohort. In the full model, considering PRS-Sz and covariates, cannabis use was also significantly associated with PLE in IMAGEN (p = 0.007). Results remained consistent in the Utrecht cohort and through sensitivity analyses. Nevertheless, there was no evidence of a mediation or moderation effects. Conclusions These results suggest that cannabis use remains a risk factor for PLEs, over and above genetic vulnerability for schizophrenia. This research does not support the notion that the cannabis-psychosis link is limited to individuals who are genetically predisposed to psychosis and suggests a need for research focusing on cannabis-related processes in psychosis that cannot be explained by genetic vulnerability.

AB - Background It has not yet been determined if the commonly reported cannabis-psychosis association is limited to individuals with pre-existing genetic risk for psychotic disorders. Methods We examined whether the relationship between polygenic risk score for schizophrenia (PRS-Sz) and psychotic-like experiences (PLEs), as measured by the Community Assessment of Psychic Experiences-42 (CAPE-42) questionnaire, is mediated or moderated by lifetime cannabis use at 16 years of age in 1740 of the individuals of the European IMAGEN cohort. Secondary analysis examined the relationships between lifetime cannabis use, PRS-Sz and the various sub-scales of the CAPE-42. Sensitivity analyses including covariates, including a PRS for cannabis use, were conducted and results were replicated using data from 1223 individuals in the Dutch Utrecht cannabis cohort. Results PRS-Sz significantly predicted cannabis use (p = 0.027) and PLE (p = 0.004) in the IMAGEN cohort. In the full model, considering PRS-Sz and covariates, cannabis use was also significantly associated with PLE in IMAGEN (p = 0.007). Results remained consistent in the Utrecht cohort and through sensitivity analyses. Nevertheless, there was no evidence of a mediation or moderation effects. Conclusions These results suggest that cannabis use remains a risk factor for PLEs, over and above genetic vulnerability for schizophrenia. This research does not support the notion that the cannabis-psychosis link is limited to individuals who are genetically predisposed to psychosis and suggests a need for research focusing on cannabis-related processes in psychosis that cannot be explained by genetic vulnerability.

KW - cannabis

KW - Polygenic risk score

KW - psychosis risk

KW - psychotic-like experience

UR - http://www.scopus.com/inward/record.url?scp=85116075973&partnerID=8YFLogxK

U2 - 10.1017/S0033291721003378

DO - 10.1017/S0033291721003378

M3 - Article

AN - SCOPUS:85116075973

SN - 0033-2917

SP - 1

EP - 11

JO - Psychological Medicine

JF - Psychological Medicine

ER -

Independent contribution of polygenic risk for schizophrenia and cannabis use in predicting psychotic-like experiences in young adulthood: Testing gene × environment moderation and mediation

Abstract

Keywords

UN SDGs

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