Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: The EU-GEI study

Monica Aas; Luis Alameda; Marta Di Forti; Diego Quattrone; Paola Dazzan; Antonella Trotta; Laura Ferraro; Victoria Rodriguez; Evangelos Vassos; Pak Sham; Giada Tripoli; Caterina La Cascia; Daniele La Barbera; Ilaria Tarricone; Roberto Muratori; Domenico Berardi; Antonio Lasalvia; Sarah Tosato; Andrei Szöke; Pierre Michel Llorca; Celso Arango; Andrea Tortelli; Lieuwe De Haan; Eva Velthorst; Julio Bobes; Miguel Bernardo; Julio Sanjuán; Jose Luis Santos; Manuel Arrojo; Cristina Marta Del-Ben; Paulo Rossi Menezes; Jean Paul Selten; Peter B. Jones; Hannah E. Jongsma; James B. Kirkbride; Bart P.F. Rutten; Jim Van Os; Charlotte Gayer-Anderson; Robin M. Murray; Craig Morgan

doi:10.1017/S0033291721003664

Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: The EU-GEI study

Monica Aas^*
, Luis Alameda
, Marta Di Forti
, Diego Quattrone
, Paola Dazzan
, Antonella Trotta
, Laura Ferraro
, Victoria Rodriguez
, Evangelos Vassos
, Pak Sham
, Giada Tripoli
, Caterina La Cascia
, Daniele La Barbera
, Ilaria Tarricone
, Roberto Muratori
, Domenico Berardi
, Antonio Lasalvia
, Sarah Tosato
, Andrei Szöke
, Pierre Michel Llorca

Celso Arango, Andrea Tortelli, Lieuwe De Haan, Eva Velthorst, Julio Bobes, Miguel Bernardo, Julio Sanjuán, Jose Luis Santos, Manuel Arrojo, Cristina Marta Del-Ben, Paulo Rossi Menezes, Jean Paul Selten, Peter B. Jones, Hannah E. Jongsma, James B. Kirkbride, Bart P.F. Rutten, Jim Van Os, Charlotte Gayer-Anderson, Robin M. Murray, Craig Morgan

^*Corresponding author for this work

Department of Basic and Clinical Neuroscience, KCL
King's College London
Service of General Psychiatry
Centre Hospitalier Universitaire Vaudois
Universidad de Sevilla
Department of Psychiatry
Hosp Univ Virgen del Rocio, Hospital Universitario Virgen del Rocio, Hospital Universitario Virgen del Rocio
University of Palermo
University of Hong Kong
Department of Medical and Surgical Science
Alma Mater Studiorum Universita di Bologna
Bologna Local Health Authority
University of Verona
U955
Université Clermont Auvergne
Hospital General Universitario Gregorio Marañón
Etablissement Public de Santé Maison Blanche
University of Amsterdam
Icahn School of Medicine at Mount Sinai
University of Oviedo
University of Barcelona
Universitat de València
Hospital Virgen de la Luz Cuenca
Complejo Hospitalario Universitario de Santiago
Universidade de Sao Paulo - USP
Rivierduinen Institute for Mental Health Care
Department of Psychiatry
UCL University College London
Maastricht University
Department of Psychiatry and Neuropsychology

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

24 Citations (Scopus)

Abstract

Background A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone. Methods We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case-control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS - ORexposure - ORPRS + 1] with adjustment for potential confounders. Results There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) -1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI -6.25 to 20.88). Conclusions Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.

Original language	English
Journal	Psychological Medicine
Volume	53
Issue number	5
DOIs	https://doi.org/10.1017/S0033291721003664
Publication status	Published - 23 Apr 2023

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Keywords

Childhood trauma
first-episode psychosis
interaction contrast ratio
polygenic risk
schizophrenia
synergistic effects

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10.1017/S0033291721003664

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Aas, M., Alameda, L., Di Forti, M., Quattrone, D., Dazzan, P., Trotta, A., Ferraro, L., Rodriguez, V., Vassos, E., Sham, P., Tripoli, G., Cascia, C. L., Barbera, D. L., Tarricone, I., Muratori, R., Berardi, D., Lasalvia, A., Tosato, S., Szöke, A., ... Morgan, C. (2023). Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: The EU-GEI study. Psychological Medicine, 53(5). https://doi.org/10.1017/S0033291721003664

@article{b9915a0215f647b583c1ad7bc1c50398,

title = "Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: The EU-GEI study",

abstract = "Background A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone. Methods We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case-control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS - ORexposure - ORPRS + 1] with adjustment for potential confounders. Results There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95\% confidence interval (CI) -1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95\% CI -6.25 to 20.88). Conclusions Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates. ",

keywords = "Childhood trauma, first-episode psychosis, interaction contrast ratio, polygenic risk, schizophrenia, synergistic effects",

author = "Monica Aas and Luis Alameda and \{Di Forti\}, Marta and Diego Quattrone and Paola Dazzan and Antonella Trotta and Laura Ferraro and Victoria Rodriguez and Evangelos Vassos and Pak Sham and Giada Tripoli and Cascia, \{Caterina La\} and Barbera, \{Daniele La\} and Ilaria Tarricone and Roberto Muratori and Domenico Berardi and Antonio Lasalvia and Sarah Tosato and Andrei Sz{\"o}ke and Llorca, \{Pierre Michel\} and Celso Arango and Andrea Tortelli and \{De Haan\}, Lieuwe and Eva Velthorst and Julio Bobes and Miguel Bernardo and Julio Sanju{\'a}n and Santos, \{Jose Luis\} and Manuel Arrojo and Del-Ben, \{Cristina Marta\} and Menezes, \{Paulo Rossi\} and Selten, \{Jean Paul\} and Jones, \{Peter B.\} and Jongsma, \{Hannah E.\} and Kirkbride, \{James B.\} and Rutten, \{Bart P.F.\} and \{Van Os\}, Jim and Charlotte Gayer-Anderson and Murray, \{Robin M.\} and Craig Morgan",

note = "Funding Information: The European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) Project is funded by grant agreement HEALTH-F2-2010-241909 (Project EU-GEI) from the European Community's Seventh Framework Programme. This study was also funded by the South-Eastern Norway Health Authority (no. 2017060), and the NARSAD Young Investigator Award to M. Aas (no. 22388). Publisher Copyright: {\textcopyright} The Author(s), 2021. Published by Cambridge University Press. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2023",

month = apr,

day = "23",

doi = "10.1017/S0033291721003664",

language = "English",

volume = "53",

journal = "Psychological Medicine",

issn = "0033-2917",

publisher = "Cambridge University Press",

number = "5",

}

Aas, M , Alameda, L , Di Forti, M , Quattrone, D , Dazzan, P , Trotta, A, Ferraro, L, Rodriguez, V , Vassos, E, Sham, P, Tripoli, G, Cascia, CL, Barbera, DL, Tarricone, I, Muratori, R, Berardi, D, Lasalvia, A, Tosato, S, Szöke, A, Llorca, PM, Arango, C, Tortelli, A, De Haan, L, Velthorst, E, Bobes, J, Bernardo, M, Sanjuán, J, Santos, JL, Arrojo, M, Del-Ben, CM, Menezes, PR, Selten, JP, Jones, PB, Jongsma, HE, Kirkbride, JB, Rutten, BPF, Van Os, J , Gayer-Anderson, C , Murray, RM & Morgan, C 2023, 'Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: The EU-GEI study', Psychological Medicine, vol. 53, no. 5. https://doi.org/10.1017/S0033291721003664

TY - JOUR

T1 - Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis

T2 - The EU-GEI study

AU - Aas, Monica

AU - Alameda, Luis

AU - Di Forti, Marta

AU - Quattrone, Diego

AU - Dazzan, Paola

AU - Trotta, Antonella

AU - Ferraro, Laura

AU - Rodriguez, Victoria

AU - Vassos, Evangelos

AU - Sham, Pak

AU - Tripoli, Giada

AU - Cascia, Caterina La

AU - Barbera, Daniele La

AU - Tarricone, Ilaria

AU - Muratori, Roberto

AU - Berardi, Domenico

AU - Lasalvia, Antonio

AU - Tosato, Sarah

AU - Szöke, Andrei

AU - Llorca, Pierre Michel

AU - Arango, Celso

AU - Tortelli, Andrea

AU - De Haan, Lieuwe

AU - Velthorst, Eva

AU - Bobes, Julio

AU - Bernardo, Miguel

AU - Sanjuán, Julio

AU - Santos, Jose Luis

AU - Arrojo, Manuel

AU - Del-Ben, Cristina Marta

AU - Menezes, Paulo Rossi

AU - Selten, Jean Paul

AU - Jones, Peter B.

AU - Jongsma, Hannah E.

AU - Kirkbride, James B.

AU - Rutten, Bart P.F.

AU - Van Os, Jim

AU - Gayer-Anderson, Charlotte

AU - Murray, Robin M.

AU - Morgan, Craig

N1 - Funding Information: The European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) Project is funded by grant agreement HEALTH-F2-2010-241909 (Project EU-GEI) from the European Community's Seventh Framework Programme. This study was also funded by the South-Eastern Norway Health Authority (no. 2017060), and the NARSAD Young Investigator Award to M. Aas (no. 22388). Publisher Copyright: © The Author(s), 2021. Published by Cambridge University Press. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2023/4/23

Y1 - 2023/4/23

N2 - Background A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone. Methods We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case-control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS - ORexposure - ORPRS + 1] with adjustment for potential confounders. Results There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) -1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI -6.25 to 20.88). Conclusions Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.

AB - Background A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone. Methods We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case-control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS - ORexposure - ORPRS + 1] with adjustment for potential confounders. Results There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) -1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI -6.25 to 20.88). Conclusions Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.

KW - Childhood trauma

KW - first-episode psychosis

KW - interaction contrast ratio

KW - polygenic risk

KW - schizophrenia

KW - synergistic effects

UR - https://www.scopus.com/pages/publications/85116599562

U2 - 10.1017/S0033291721003664

DO - 10.1017/S0033291721003664

M3 - Article

AN - SCOPUS:85116599562

SN - 0033-2917

VL - 53

JO - Psychological Medicine

JF - Psychological Medicine

IS - 5

ER -

Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: The EU-GEI study

Abstract

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Keywords

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