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1. The relationship between genetic liability, childhood maltreatment, and IQ: findings from the EU-GEI multicentric case–control study

Author

Sideli, Lucia, Aas, Monica, Quattrone, Diego, La Barbera, Daniele, La Cascia, Caterina, Ferraro, Laura, Alameda, Luis, Velthorst, Eva, Trotta, Giulia, Tripoli, Giada, Schimmenti, Adriano, Fontana, Andrea, Gayer-Anderson, Charlotte, Stilo, Simona, Seminerio, Fabio, Sartorio, Crocettarachele, Marrazzo, Giovanna, Lasalvia, Antonio, Tosato, Sarah, Tarricone, Ilaria, Berardi, Domenico, D’Andrea, Giuseppe, Arango, Celso, Arrojo, Manuel, Bernardo, Miguel, Bobes, Julio, Sanjuán, Julio, Santos, Jose Luis, Menezes, Paulo Rossi, Del-Ben, Cristina Marta, Jongsma, Hannah E., Jones, Peter B., Kirkbride, James B., Llorca, Pierre-Michel, Tortelli, Andrea, Pignon, Baptiste, de Haan, Lieuwe, Selten, Jean-Paul, Van Os, Jim, Rutten, Bart P., Bentall, Richard, Di Forti, Marta, Murray, Robin M., Morgan, Craig, and Fisher, Helen L.

Published
2023
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2. Psychological distress and suicidal ideation in Sicilian Medical Students: The SMS-ME project

Author

Bonaccorso, Nicole, Tripoli, Giada, Vella, Ilaria, La Cascia, Caterina, Amodio, Emanuele, Bongiorno, Eleonora, Genovese, Dario, Maniaci, Giuseppe, Sciortino, Martina, Galatà, Elisa, Iacono, Giorgia, Romano, Alessandra, Guglielmino, Damiano, Seminerio, Fabio, Sartorio, Crocettarachele, Scaglione, Alessandra, Silvestri, Maria Catena, Baido, Rosa Lo, Quattropani, Maria Catena, Muscatello, Maria Rosaria Anna, Mento, Carmela, Signorelli, Maria Salvina, Quattrone, Diego, Vitale, Francesco, La Barbera, Daniele, Costantino, Claudio, and Ferraro, Laura

Published
2024
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3. Exploring the mediation of DNA methylation across the epigenome between childhood adversity and First Episode of Psychosis—findings from the EU-GEI study

Author

Alameda, Luis, Liu, Zhonghua, Sham, Pak C., Aas, Monica, Trotta, Giulia, Rodriguez, Victoria, Di Forti, Marta, Stilo, Simona A., Kandaswamy, Radhika, Arango, Celso, Arrojo, Manuel, Bernardo, Miguel, Bobes, Julio, de Haan, Lieuwe, Del-Ben, Cristina Marta, Gayer-Anderson, Charlotte, Sideli, Lucia, Jones, Peter B., Jongsma, Hannah E., Kirkbride, James B., La Cascia, Caterina, Lasalvia, Antonio, Tosato, Sarah, Llorca, Pierre-Michel, Menezes, Paulo Rossi, van Os, Jim, Quattrone, Diego, Rutten, Bart P., Santos, Jose Luis, Sanjuán, Julio, Selten, Jean-Paul, Szöke, Andrei, Tarricone, Ilaria, Tortelli, Andrea, Velthorst, Eva, Morgan, Craig, Dempster, Emma, Hannon, Eilis, Burrage, Joe, Dwir, Daniella, Arumuham, Atheeshaan, Mill, Jonathan, Murray, Robin M., and Wong, Chloe C. Y.

Published
2023
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6. The impact of cannabis use and polygenic risk scores on symptom dimension profiles at psychosis onset

Author

Quattrone, Diego, Di Forti, Marta, Murray, Robin MacGregor, Lewis, Cathryn Mair, and Reininghaus, Ulrich

Subjects
615.7
Abstract

Introduction: Epidemiological and biological evidence show no boundaries between diagnostic categories of non-affective and affective psychoses, thus challenging the current nosological model developed from Kraepelin’s paradigm. My thesis aimed to address this limitation by 1) examining the transdiagnostic dimensional structure of i) psychotic symptoms in first episode psychosis (FEP) patients and ii) psychotic experiences in the general population; 2) investigating the relationship between these dimensions and a set of external factors, such as the use of cannabis and genetic common variant liability for psychotic disorders. Overall, I expected that differences in symptom profiles at FEP reflected gradients of neurodevelopmental impairment in psychosis. Methods: This thesis uses data from a multisite incidence and case-control study, which I worked on, conducted across six countries [i.e. the ‘European Network of National Schizophrenia Networks studying Gene-Environment Interactions’ (EU-GEI) study]. To examine the latent structure of psychopathology, I analysed ratings of psychotic symptoms and experiences using multidimensional item response modelling in Mplus, and I estimated different theory-based models of psychosis, including unidimensional, multidimensional, bifactor, and hierarchical solutions. To examine the common variant liability to psychosis, I examined the population structure in the EU-GEI sample and computed ancestry-specific schizophrenia (SZ), bipolar disorder 7 (BP), and combined schizophrenia-bipolar disorder (SZ-BP) Polygenic Risk Scores (PRSs) in PRSice. To examine the relationship between the latent structure of psychopathology and demographic and context determinants, detailed patterns of cannabis consumption, and PRSs, I used multiple linear regression models fitted in STATA14. Results: The associations among ratings of both psychotic symptoms in FEP patients and psychotic experiences in population-based controls were best represented by a bifactor model, composed of one general psychosis factor and multiple specific dimensions. In FEP patients, the examination of general and specific dimensions with external factors showed that 1) higher scores on the negative symptom dimension were associated with being a male, and having never used cannabis; 2) higher scores on the positive symptom dimension were associated with exposure to socioenvironmental risk factors in psychosis, such as being part of an ethnic minority, and having had exposure to cannabis in a dose-response fashion, with those having used high potency varieties on a daily basis having the highest score; 3) both higher scores on the positive and negative symptom dimensions were associated with a higher SZ-PRS. In population-based controls, the examination of general and specific dimensions with external factors showed that 1) higher scores on the positive psychotic experience dimension were associated with current use of cannabis but not with the extent of lifetime exposure to cannabis; 2) higher scores on the general and all the specific psychotic experience dimensions were associated with a high SZ-PRS. Conclusions: My thesis shows that symptom dimensions are useful psychosis phenotypes, that are validated by psychometric data and socioenvironmental and genetic factors. Specifically, the bifactor model of psychopathology holds across diagnostic categories of non-affective and affective psychosis at FEP and in the general population. Furthermore, my findings indicate that use of cannabis is associated with more positive and less negative symptoms at FEP, consistently with the hypothesis that cannabis users who develop psychosis have less early neurodevelopmental impairment than their non-user counterparts. Overall, these findings indicate that it is appropriate to conduct research using enhanced phenotypes, and they have translational relevance, they are important for developing secondary prevention strategies in psychosis. Currently, symptom dimensions at FEP could be used for formulating clinical impressions regardless of diagnostic categories according to a developmental-symptom approach, and for guiding tailored treatments.

Published
2020

7. The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia

Author

Richards, Alexander L, Pardiñas, Antonio F, Frizzati, Aura, Tansey, Katherine E, Lynham, Amy J, Holmans, Peter, Legge, Sophie E, Savage, Jeanne E, Agartz, Ingrid, Andreassen, Ole A, Blokland, Gabriella AM, Corvin, Aiden, Cosgrove, Donna, Degenhardt, Franziska, Djurovic, Srdjan, Espeseth, Thomas, Ferraro, Laura, Gayer-Anderson, Charlotte, Giegling, Ina, van Haren, Neeltje E, Hartmann, Annette M, Hubert, John J, Jönsson, Erik G, Konte, Bettina, Lennertz, Leonhard, Olde Loohuis, Loes M, Melle, Ingrid, Morgan, Craig, Morris, Derek W, Murray, Robin M, Nyman, Håkan, Ophoff, Roel A, van Os, Jim, Petryshen, Tracey L, Quattrone, Diego, Rietschel, Marcella, Rujescu, Dan, Rutten, Bart PF, Streit, Fabian, Strohmaier, Jana, Sullivan, Patrick F, Sundet, Kjetil, Wagner, Michael, Escott-Price, Valentina, Owen, Michael J, Donohoe, Gary, O’Donovan, Michael C, and Walters, James TR

Subjects
Genetics, Prevention, Schizophrenia, Depression, Behavioral and Social Science, Mental Health, Brain Disorders, Serious Mental Illness, Human Genome, 2.1 Biological and endogenous factors, Aetiology, 2.3 Psychological, social and economic factors, Mental health, Bipolar Disorder, Datasets as Topic, Depressive Disorder, Major, Educational Status, Genome-Wide Association Study, Humans, Intelligence, Multifactorial Inheritance, Psychotic Disorders, psychiatry, genomics, intelligence, bioinformatics, GROUP Investigators, EUGEI WP2 Group, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

BackgroundCognitive impairment is a clinically important feature of schizophrenia. Polygenic risk score (PRS) methods have demonstrated genetic overlap between schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), educational attainment (EA), and IQ, but very few studies have examined associations between these PRS and cognitive phenotypes within schizophrenia cases.MethodsWe combined genetic and cognitive data in 3034 schizophrenia cases from 11 samples using the general intelligence factor g as the primary measure of cognition. We used linear regression to examine the association between cognition and PRS for EA, IQ, schizophrenia, BD, and MDD. The results were then meta-analyzed across all samples. A genome-wide association studies (GWAS) of cognition was conducted in schizophrenia cases.ResultsPRS for both population IQ (P = 4.39 × 10-28) and EA (P = 1.27 × 10-26) were positively correlated with cognition in those with schizophrenia. In contrast, there was no association between cognition in schizophrenia cases and PRS for schizophrenia (P = .39), BD (P = .51), or MDD (P = .49). No individual variant approached genome-wide significance in the GWAS.ConclusionsCognition in schizophrenia cases is more strongly associated with PRS that index cognitive traits in the general population than PRS for neuropsychiatric disorders. This suggests the mechanisms of cognitive variation within schizophrenia are at least partly independent from those that predispose to schizophrenia diagnosis itself. Our findings indicate that this cognitive variation arises at least in part due to genetic factors shared with cognitive performance in populations and is not solely due to illness or treatment-related factors, although our findings are consistent with important contributions from these factors.

Published
2020

8. The Role of Social Deprivation and Cannabis Use in Explaining Variation in the Incidence of Psychotic Disorders: Findings From the EU-GEI Study

Author

Brink, Vera, primary, Andleeb, Humma, additional, Gayer-Anderson, Charlotte, additional, Arango, Celso, additional, Arrojo, Manuel, additional, Berardi, Domenico, additional, Bernardo, Miquel, additional, Bobes, Julio, additional, Del-Ben, Cristina Marta, additional, Ferraro, Laura, additional, de Haan, Lieuwe, additional, La Barbera, Daniele, additional, La Cascia, Caterina, additional, Lasalvia, Antonio, additional, Llorca, Pierre-Michel, additional, Menezes, Paolo Rossi, additional, Pignon, Baptiste, additional, Sanjuán, Julio, additional, Santos, José Luis, additional, Selten, Jean-Paul, additional, Tarricone, Ilaria, additional, Tortelli, Andrea, additional, Tripoli, Giada, additional, Velthorst, Eva, additional, Rutten, Bart P F, additional, van Os, Jim, additional, Quattrone, Diego, additional, Murray, Robin M, additional, Jones, Peter B, additional, Morgan, Craig, additional, Di Forti, Marta, additional, Jongsma, Hannah E, additional, and Kirkbride, James B, additional

Published
2024
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11. The effect of polygenic risk score and childhood adversity experiences on transdiagnostic symptom dimensions at first-episode psychosis: evidence for an affective pathway to psychosis

Author

Alameda, Luis, primary, Pérez, Victoria, additional, Forti, Marta di, additional, Spinazzola, Edoardo, additional, Trotta, Giulia, additional, Arango, Celso, additional, Arrojo, Manuel, additional, Bernardo, Miguel, additional, Bobes, Julio, additional, Gayer-Anderson, Charlotte, additional, Del-Ben, Cristina Marta, additional, Sideli, Lucia, additional, Jones, Peter, additional, Kirkbride, James, additional, Cascia, Caterina La, additional, Tripoli, Giada, additional, Ferraro, Laura, additional, Barbera, Daniele La, additional, Lasalvia, Antonio, additional, Tosato, Sarah, additional, Llorca, Pierre Michel, additional, Menezes, Paulo, additional, Os, Jim van, additional, Rutten, Bart, additional, Santos, Jose, additional, Sanjuan, Julio, additional, Selten, Jean-Paul, additional, Szöke, Andrei, additional, Tarricone, Ilaria, additional, Tortelli, Andrea, additional, Velthorst, Eva, additional, Johgsma, Hannah E., additional, Vassos, Evangelos, additional, Quattrone, Diego, additional, Murray, Robin, additional, and Aas, Monica, additional

Published
2024
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12. Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Author

Trubetskoy, Vassily, Pardiñas, Antonio F., Qi, Ting, Panagiotaropoulou, Georgia, Awasthi, Swapnil, Bigdeli, Tim B., Bryois, Julien, Chen, Chia-Yen, Dennison, Charlotte A., Hall, Lynsey S., Lam, Max, Watanabe, Kyoko, Frei, Oleksandr, Ge, Tian, Harwood, Janet C., Koopmans, Frank, Magnusson, Sigurdur, Richards, Alexander L., Sidorenko, Julia, Wu, Yang, Zeng, Jian, Grove, Jakob, Kim, Minsoo, Li, Zhiqiang, Voloudakis, Georgios, Zhang, Wen, Adams, Mark, Agartz, Ingrid, Atkinson, Elizabeth G., Agerbo, Esben, Al Eissa, Mariam, Albus, Margot, Alexander, Madeline, Alizadeh, Behrooz Z., Alptekin, Köksal, Als, Thomas D., Amin, Farooq, Arolt, Volker, Arrojo, Manuel, Athanasiu, Lavinia, Azevedo, Maria Helena, Bacanu, Silviu A., Bass, Nicholas J., Begemann, Martin, Belliveau, Richard A., Bene, Judit, Benyamin, Beben, Bergen, Sarah E., Blasi, Giuseppe, Bobes, Julio, Bonassi, Stefano, Braun, Alice, Bressan, Rodrigo Affonseca, Bromet, Evelyn J., Bruggeman, Richard, Buckley, Peter F., Buckner, Randy L., Bybjerg-Grauholm, Jonas, Cahn, Wiepke, Cairns, Murray J., Calkins, Monica E., Carr, Vaughan J., Castle, David, Catts, Stanley V., Chambert, Kimberley D., Chan, Raymond C. K., Chaumette, Boris, Cheng, Wei, Cheung, Eric F. C., Chong, Siow Ann, Cohen, David, Consoli, Angèle, Cordeiro, Quirino, Costas, Javier, Curtis, Charles, Davidson, Michael, Davis, Kenneth L., de Haan, Lieuwe, Degenhardt, Franziska, DeLisi, Lynn E., Demontis, Ditte, Dickerson, Faith, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Duan, Jubao, Ducci, Giuseppe, Dudbridge, Frank, Eriksson, Johan G., Fañanás, Lourdes, Faraone, Stephen V., Fiorentino, Alessia, Forstner, Andreas, Frank, Josef, Freimer, Nelson B., Fromer, Menachem, Frustaci, Alessandra, Gadelha, Ary, Genovese, Giulio, Gershon, Elliot S., Giannitelli, Marianna, Giegling, Ina, Giusti-Rodríguez, Paola, Godard, Stephanie, Goldstein, Jacqueline I., González Peñas, Javier, González-Pinto, Ana, Gopal, Srihari, Gratten, Jacob, Green, Michael F., Greenwood, Tiffany A., Guillin, Olivier, Gülöksüz, Sinan, Gur, Raquel E., Gur, Ruben C., Gutiérrez, Blanca, Hahn, Eric, Hakonarson, Hakon, Haroutunian, Vahram, Hartmann, Annette M., Harvey, Carol, Hayward, Caroline, Henskens, Frans A., Herms, Stefan, Hoffmann, Per, Howrigan, Daniel P., Ikeda, Masashi, Iyegbe, Conrad, Joa, Inge, Julià, Antonio, Kähler, Anna K., Kam-Thong, Tony, Kamatani, Yoichiro, Karachanak-Yankova, Sena, Kebir, Oussama, Keller, Matthew C., Kelly, Brian J., Khrunin, Andrey, Kim, Sung-Wan, Klovins, Janis, Kondratiev, Nikolay, Konte, Bettina, Kraft, Julia, Kubo, Michiaki, Kučinskas, Vaidutis, Kučinskiene, Zita Ausrele, Kusumawardhani, Agung, Kuzelova-Ptackova, Hana, Landi, Stefano, Lazzeroni, Laura C., Lee, Phil H., Legge, Sophie E., Lehrer, Douglas S., Lencer, Rebecca, Lerer, Bernard, Li, Miaoxin, Lieberman, Jeffrey, Light, Gregory A., Limborska, Svetlana, Liu, Chih-Min, Lönnqvist, Jouko, Loughland, Carmel M., Lubinski, Jan, Luykx, Jurjen J., Lynham, Amy, Macek, Jr, Milan, Mackinnon, Andrew, Magnusson, Patrik K. E., Maher, Brion S., Maier, Wolfgang, Malaspina, Dolores, Mallet, Jacques, Marder, Stephen R., Marsal, Sara, Martin, Alicia R., Martorell, Lourdes, Mattheisen, Manuel, McCarley, Robert W., McDonald, Colm, McGrath, John J., Medeiros, Helena, Meier, Sandra, Melegh, Bela, Melle, Ingrid, Mesholam-Gately, Raquelle I., Metspalu, Andres, Michie, Patricia T., Milani, Lili, Milanova, Vihra, Mitjans, Marina, Molden, Espen, Molina, Esther, Molto, María Dolores, Mondelli, Valeria, Moreno, Carmen, Morley, Christopher P., Muntané, Gerard, Murphy, Kieran C., Myin-Germeys, Inez, Nenadić, Igor, Nestadt, Gerald, Nikitina-Zake, Liene, Noto, Cristiano, Nuechterlein, Keith H., O’Brien, Niamh Louise, O’Neill, F. Anthony, Oh, Sang-Yun, Olincy, Ann, Ota, Vanessa Kiyomi, Pantelis, Christos, Papadimitriou, George N., Parellada, Mara, Paunio, Tiina, Pellegrino, Renata, Periyasamy, Sathish, Perkins, Diana O., Pfuhlmann, Bruno, Pietiläinen, Olli, Pimm, Jonathan, Porteous, David, Powell, John, Quattrone, Diego, Quested, Digby, Radant, Allen D., Rampino, Antonio, Rapaport, Mark H., Rautanen, Anna, Reichenberg, Abraham, Roe, Cheryl, Roffman, Joshua L., Roth, Julian, Rothermundt, Matthias, Rutten, Bart P. F., Saker-Delye, Safaa, Salomaa, Veikko, Sanjuan, Julio, Santoro, Marcos Leite, Savitz, Adam, Schall, Ulrich, Scott, Rodney J., Seidman, Larry J., Sharp, Sally Isabel, Shi, Jianxin, Siever, Larry J., Sigurdsson, Engilbert, Sim, Kang, Skarabis, Nora, Slominsky, Petr, So, Hon-Cheong, Sobell, Janet L., Söderman, Erik, Stain, Helen J., Steen, Nils Eiel, Steixner-Kumar, Agnes A., Stögmann, Elisabeth, Stone, William S., Straub, Richard E., Streit, Fabian, Strengman, Eric, Stroup, T. Scott, Subramaniam, Mythily, Sugar, Catherine A., Suvisaari, Jaana, Svrakic, Dragan M., Swerdlow, Neal R., Szatkiewicz, Jin P., Ta, Thi Minh Tam, Takahashi, Atsushi, Terao, Chikashi, Thibaut, Florence, Toncheva, Draga, Tooney, Paul A., Torretta, Silvia, Tosato, Sarah, Tura, Gian Battista, Turetsky, Bruce I., Üçok, Alp, Vaaler, Arne, van Amelsvoort, Therese, van Winkel, Ruud, Veijola, Juha, Waddington, John, Walter, Henrik, Waterreus, Anna, Webb, Bradley T., Weiser, Mark, Williams, Nigel M., Witt, Stephanie H., Wormley, Brandon K., Wu, Jing Qin, Xu, Zhida, Yolken, Robert, Zai, Clement C., Zhou, Wei, Zhu, Feng, Zimprich, Fritz, Atbaşoğlu, Eşref Cem, Ayub, Muhammad, Benner, Christian, Bertolino, Alessandro, Black, Donald W., Bray, Nicholas J., Breen, Gerome, Buccola, Nancy G., Byerley, William F., Chen, Wei J., Cloninger, C. Robert, Crespo-Facorro, Benedicto, Donohoe, Gary, Freedman, Robert, Galletly, Cherrie, Gandal, Michael J., Gennarelli, Massimo, Hougaard, David M., Hwu, Hai-Gwo, Jablensky, Assen V., McCarroll, Steven A., Moran, Jennifer L., Mors, Ole, Mortensen, Preben B., Müller-Myhsok, Bertram, Neil, Amanda L., Nordentoft, Merete, Pato, Michele T., Petryshen, Tracey L., Pirinen, Matti, Pulver, Ann E., Schulze, Thomas G., Silverman, Jeremy M., Smoller, Jordan W., Stahl, Eli A., Tsuang, Debby W., Vilella, Elisabet, Wang, Shi-Heng, Xu, Shuhua, Adolfsson, Rolf, Arango, Celso, Baune, Bernhard T., Belangero, Sintia Iole, Børglum, Anders D., Braff, David, Bramon, Elvira, Buxbaum, Joseph D., Campion, Dominique, Cervilla, Jorge A., Cichon, Sven, Collier, David A., Corvin, Aiden, Curtis, David, Forti, Marta Di, Domenici, Enrico, Ehrenreich, Hannelore, Escott-Price, Valentina, Esko, Tõnu, Fanous, Ayman H., Gareeva, Anna, Gawlik, Micha, Gejman, Pablo V., Gill, Michael, Glatt, Stephen J., Golimbet, Vera, Hong, Kyung Sue, Hultman, Christina M., Hyman, Steven E., Iwata, Nakao, Jönsson, Erik G., Kahn, René S., Kennedy, James L., Khusnutdinova, Elza, Kirov, George, Knowles, James A., Krebs, Marie-Odile, Laurent-Levinson, Claudine, Lee, Jimmy, Lencz, Todd, Levinson, Douglas F., Li, Qingqin S., Liu, Jianjun, Malhotra, Anil K., Malhotra, Dheeraj, McIntosh, Andrew, McQuillin, Andrew, Menezes, Paulo R., Morgan, Vera A., Morris, Derek W., Mowry, Bryan J., Murray, Robin M., Nimgaonkar, Vishwajit, Nöthen, Markus M., Ophoff, Roel A., Paciga, Sara A., Palotie, Aarno, Pato, Carlos N., Qin, Shengying, Rietschel, Marcella, Riley, Brien P., Rivera, Margarita, Rujescu, Dan, Saka, Meram C., Sanders, Alan R., Schwab, Sibylle G., Serretti, Alessandro, Sham, Pak C., Shi, Yongyong, St Clair, David, Stefánsson, Hreinn, Stefansson, Kari, Tsuang, Ming T., van Os, Jim, Vawter, Marquis P., Weinberger, Daniel R., Werge, Thomas, Wildenauer, Dieter B., Yu, Xin, Yue, Weihua, Holmans, Peter A., Pocklington, Andrew J., Roussos, Panos, Vassos, Evangelos, Verhage, Matthijs, Visscher, Peter M., Yang, Jian, Posthuma, Danielle, Andreassen, Ole A., Kendler, Kenneth S., Owen, Michael J., Wray, Naomi R., Daly, Mark J., Huang, Hailiang, Neale, Benjamin M., Sullivan, Patrick F., Ripke, Stephan, Walters, James T. R., and O’Donovan, Michael C.

Published
2022
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14. Variation of subclinical psychosis across 16 sites in Europe and Brazil: findings from the multi-national EU-GEI study.

Author

D'Andrea, Giuseppe, Quattrone, Diego, Malone, Kathryn, Tripoli, Giada, Trotta, Giulia, Spinazzola, Edoardo, Gayer-Anderson, Charlotte, Jongsma, Hannah E, Sideli, Lucia, Stilo, Simona A, La Cascia, Caterina, Ferraro, Laura, Lasalvia, Antonio, Tosato, Sarah, Tortelli, Andrea, Velthorst, Eva, de Haan, Lieuwe, Llorca, Pierre-Michel, Rossi Menezes, Paulo, and Santos, Jose Luis

Subjects
*SCHIZOTYPAL personality disorder, *ECOLOGY, *RESEARCH funding, *MULTIPLE regression analysis, *SEX distribution, *NOMADS, *SOCIOECONOMIC factors, *DESCRIPTIVE statistics, *AGE distribution, *RESEARCH, *MATHEMATICAL models, *PSYCHOSES, *THEORY, *COMPARATIVE studies, *CANNABIS (Genus), *SOCIODEMOGRAPHIC factors, *PHENOTYPES, *DISEASE incidence, *ADVERSE childhood experiences, *EMPLOYMENT
Abstract

Background: Incidence of first-episode psychosis (FEP) varies substantially across geographic regions. Phenotypes of subclinical psychosis (SP), such as psychotic-like experiences (PLEs) and schizotypy, present several similarities with psychosis. We aimed to examine whether SP measures varied across different sites and whether this variation was comparable with FEP incidence within the same areas. We further examined contribution of environmental and genetic factors to SP. Methods: We used data from 1497 controls recruited in 16 different sites across 6 countries. Factor scores for several psychopathological dimensions of schizotypy and PLEs were obtained using multidimensional item response theory models. Variation of these scores was assessed using multi-level regression analysis to estimate individual and between-sites variance adjusting for age, sex, education, migrant, employment and relational status, childhood adversity, and cannabis use. In the final model we added local FEP incidence as a second-level variable. Association with genetic liability was examined separately. Results: Schizotypy showed a large between-sites variation with up to 15% of variance attributable to site-level characteristics. Adding local FEP incidence to the model considerably reduced the between-sites unexplained schizotypy variance. PLEs did not show as much variation. Overall, SP was associated with younger age, migrant, unmarried, unemployed and less educated individuals, cannabis use, and childhood adversity. Both phenotypes were associated with genetic liability to schizophrenia. Conclusions: Schizotypy showed substantial between-sites variation, being more represented in areas where FEP incidence is higher. This supports the hypothesis that shared contextual factors shape the between-sites variation of psychosis across the spectrum. [ABSTRACT FROM AUTHOR]

Published
2024
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16. The relationship of symptom dimensions with premorbid adjustment and cognitive characteristics at first episode psychosis: Findings from the EU-GEI study

Author

Ferraro, Laura, La Cascia, Caterina, La Barbera, Daniele, Sanchez-Gutierrez, Teresa, Tripoli, Giada, Seminerio, Fabio, Sartorio, Crocettarachele, Marrazzo, Giovanna, Sideli, Lucia, Arango, Celso, Arrojo, Manuel, Bernardo, Miguel, Bobes, Julio, Del-Ben, Cristina Marta, Gayer-Anderson, Charlotte, Jongsma, Hannah E., Kirkbride, James B., Lasalvia, Antonio, Tosato, Sarah, Llorca, Pierre-Michel, Menezes, Paulo Rossi, Rutten, Bart P., Santos, Jose Luis, Sanjuán, Julio, Selten, Jean-Paul, Szöke, Andrei, Tarricone, Ilaria, Muratori, Roberto, Tortelli, Andrea, Velthorst, Eva, Rodriguez, Victoria, Quattrone, Andrea, Jones, Peter B., Van Os, Jim, Vassos, Evangelos, Morgan, Craig, de Haan, Lieuwe, Reininghaus, Ulrich, Cardno, Alastair G., Di Forti, Marta, Murray, Robin M., and Quattrone, Diego

Published
2021
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18. Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings

Author

Velthorst, Eva, Mollon, Josephine, Murray, Robin M., de Haan, Lieuwe, Germeys, Inez Myin, Glahn, David C., Arango, Celso, van der Ven, Els, Di Forti, Marta, Bernardo, Miguel, Guloksuz, Sinan, Delespaul, Philippe, Mezquida, Gisela, Amoretti, Silvia, Bobes, Julio, Saiz, Pilar A., García-Portilla, María Paz, Santos, José Luis, Jiménez-López, Estela, Sanjuan, Julio, Aguilar, Eduardo J., Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Atbaşoğlu, Cem, Saka, Meram Can, Üçok, Alp, Alptekin, Köksal, Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Ulaş, Halis, Yalınçetin, Berna, Gümüş-Akay, Güvem, Beyaz, Burçin Cihan, Soygür, Haldun, Cankurtaran, Eylem Şahin, Kaymak, Semra Ulusoy, Maric, Nadja P., Mihaljevic, Marina M., Petrovic, Sanja Andric, Mirjanic, Tijana, Del-Ben, Cristina Marta, Ferraro, Laura, Gayer-Anderson, Charlotte, Jones, Peter B., Jongsma, Hannah E., Kirkbride, James B., La Cascia, Caterina, Lasalvia, Antonio, Tosato, Sarah, Llorca, Pierre-Michel, Menezes, Paulo Rossi, Morgan, Craig, Quattrone, Diego, Menchetti, Marco, Selten, Jean-Paul, Szöke, Andrei, Tarricone, Ilaria, Tortelli, Andrea, McGuire, Philip, Valmaggia, Lucia, Kempton, Matthew J., van der Gaag, Mark, Riecher-Rössler, Anita, Bressan, Rodrigo A., Barrantes-Vidal, Neus, Nelson, Barnaby, McGorry, Patrick, Pantelis, Chris, Krebs, Marie-Odile, Ruhrmann, Stephan, Sachs, Gabriele, Rutten, Bart P. F., van Os, Jim, Alizadeh, Behrooz Z., van Amelsvoort, Therese, Bartels-Velthuis, Agna A., Bruggeman, Richard, van Beveren, Nico J., Luykx, Jurjen J., Cahn, Wiepke, Simons, Claudia J. P., Kahn, Rene S., Schirmbeck, Frederike, van Winkel, Ruud, and Reichenberg, Abraham

Published
2021
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19. Methylomic signature of current cannabis use in two first-episode psychosis cohorts

Author

Dempster, Emma, primary, Wong, Chloe, additional, Burrage, Joe, additional, Hannon, Eilis, additional, Quattrone, Diego, additional, Giulia, Trotta, additional, Rodriguez, Victoria, additional, Spinazzola, Edoardo, additional, Tripoli, Giada, additional, Austin-Zimmerman, Isabelle, additional, Li, Z, additional, Gayer-Anderson, Charlotte, additional, Freeman, Tom, additional, Johnson, Emma, additional, Jongsma, Hannah, additional, Simona, Stilo, additional, Cascia, Caterina La, additional, Ferraro, Laura, additional, Barbera, Daniele La, additional, Lasalvia, Antonio, additional, Tosato, Sarah, additional, Tarricone, Ilaria, additional, D’Andrea, Giuseppe, additional, Galatolo, Michela, additional, Tortelli, Andrea, additional, Arango, Celso, additional, Jones, Peter, additional, Pompili, Maurizio, additional, Selten, Jean-Paul, additional, de Haan, Lieuwe, additional, Menezes, Paulo, additional, Del-Ben, Cristina Marta, additional, Santos, José, additional, Arrojo, Manuel, additional, Bobes, Julio, additional, Sanjuan, Julio, additional, Bernardo, Miquel, additional, Breen, Gerome, additional, Mondelli, Valeria, additional, Dazzan, Paola, additional, Iyegbe, Conrad, additional, Vassos, Evangelos, additional, Morgan, Craig, additional, Mukherjee, Diptendu, additional, Os, Jim van, additional, Rutten, Bart, additional, O'Donovan, Michael, additional, Sham, Pak, additional, Mill, Jonathan, additional, Murray, Robin, additional, Forti, Marta di, additional, and Alameda, Luis, additional

Published
2023
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22. The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a multicentre case-control study

Author

Amoretti, Silvia, Arrojo, Manuel, Baudin, Grégoire, Beards, Stephanie, Bernardo, Miquel, Bobes, Julio, Bonetto, Chiara, Cabrera, Bibiana, Carracedo, Angel, Charpeaud, Thomas, Costas, Javier, Cristofalo, Doriana, Cuadrado, Pedro, Díaz-Caneja, Covadonga M, Ferchiou, Aziz, Franke, Nathalie, Frijda, Flora, García Bernardo, Enrique, Garcia-Portilla, Paz, González, Emiliano, Hubbard, Kathryn, Jamain, Stéphane, Jiménez-López, Estela, Leboyer, Marion, López Montoya, Gonzalo, Lorente-Rovira, Esther, Marcelino Loureiro, Camila, Marrazzo, Giovanna, Martínez, Covadonga, Matteis, Mario, Messchaart, Elles, Moltó, Ma Dolores, Nacher, Juan, Olmeda, Ma Soledad, Parellada, Mara, González Peñas, Javier, Pignon, Baptiste, Rapado, Marta, Richard, Jean-Romain, Rodríguez Solano, José Juan, Roldán Díaz, Laura, Ruggeri, Mirella, Sáiz, Pilar A., Sánchez, Emilio, Sanjuán, Julio, Sartorio, Crocettarachele, Schürhoff, Franck, Seminerio, Fabio, Shuhama, Rosana, Sideli, Lucia, Stilo, Simona A, Termorshuizen, Fabian, Tosato, Sarah, Tronche, Anne-Marie, van Dam, Daniella, van der Ven, Elsje, Di Forti, Marta, Quattrone, Diego, Freeman, Tom P, Tripoli, Giada, Gayer-Anderson, Charlotte, Quigley, Harriet, Rodriguez, Victoria, Jongsma, Hannah E, Ferraro, Laura, La Cascia, Caterina, La Barbera, Daniele, Tarricone, Ilaria, Berardi, Domenico, Szöke, Andrei, Arango, Celso, Tortelli, Andrea, Velthorst, Eva, Bernardo, Miguel, Del-Ben, Cristina Marta, Menezes, Paulo Rossi, Selten, Jean-Paul, Jones, Peter B, Kirkbride, James B, Rutten, Bart PF, de Haan, Lieuwe, Sham, Pak C, van Os, Jim, Lewis, Cathryn M, Lynskey, Michael, Morgan, Craig, and Murray, Robin M

Published
2019
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26. Post-migration trajectories and psychopathological vulnerability

Author

Tarricone, I., primary, Tarricone, Ilaria, additional, D’Andrea, Giuseppe, additional, Jongsma, Hannah E, additional, Tosato, Sarah, additional, Gayer-Anderson, Charlotte, additional, Stilo, Simona A., additional, Suprani, Federico, additional, Iyegbe, Conrad, additional, van der Ven, Els, additional, Quattrone, Diego, additional, di Forti, Marta, additional, Velthorst, Eva, additional, Menezes, Paulo Rossi, additional, Arango, Celso, additional, and Parel, Mara, additional

Published
2023
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27. Systematic review and meta-analysis on the effects of chronic peri-adolescent cannabinoid exposure on schizophrenia-like behaviour in rodents

Author

Li, Zhikun, Mukherjee, Diptendu, Duric, Bea, Austin-Zimmerman, Isabelle, Trotta, Giulia, Spinazzola, Edoardo, Quattrone, Diego, Murray, Robin M., and Di Forti, Marta

Abstract

Background: The link between cannabis use and schizophrenia is well-established in epidemiological studies, especially among adolescents with early-onset use. However, this association in rodent models is less clear. This meta-analysis examined the effects of adolescent cannabinoid exposure on distinct schizophrenia-like behaviours in rodents and how experimental variations influence outcomes. Methods: Following a pre-registered protocol (CRD42022338761), we searched PubMed, Ovid Medline, Embse and APA PsychInfo for English-language original studies until May 2024. We synthesised data from experiments on schizophrenia-like behaviour in rats and mice after repeated peri-pubertal (onset between P23-P45) cannabinoid exposure. Risk of bias was assessed using the SYRCLE’s tool. Results: We included 359 experiments from 108 articles across 9 behavioural tests. We found meta-analytic evidence supporting that CB1R agonists, both natural and synthetic, elicited broad schizophrenia-like behavioural alterations, including impaired working memory [g= −0.56; (CI: −0.93, −0.18)], novel object recognition [g= −0.66; (CI: −0.97, −0.35)], novel object location recognition [g= −0.70; (CI: −1.07, −0.33]), social novelty preference [g= −0.52; (CI: −0.93, −0.11)], social motivation [g= −0.21; (CI: −0.42, −0.00)], pre-pulse inhibition [g= −0.43; (CI: −0.76, −0.10)], and sucrose preference [g= −0.87; (CI: −1.46, −0.27)]. By contrast, effects on novelty-induced locomotion were negligible. Subgroup analyses revealed similar effects across sexes and species. Substantial variance in the protocols and moderate-to-high heterogeneity in behavioural outcomes were observed. We found CBD may enhance fear memory recall, but data was limited. Discussion: This is the first meta-analysis to comprehensively assess the link between cannabinoids and schizophrenia-like behaviours in rodents. Our results support epidemiological links between early cannabis use and schizophrenia-like phenotypes, confirming the utility of animal models. Standardising protocols will optimise models to strengthen reproducibility and comparisons, our work provides a framework for refining rodent models to elucidate biological pathways linking cannabis and schizophrenia.

Published
2024
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29. The association between reasons for first using cannabis, later pattern of use, and risk of first-episode psychosis: the EU-GEI case–control study.

Author

Spinazzola, Edoardo, Quattrone, Diego, Rodriguez, Victoria, Trotta, Giulia, Alameda, Luis, Tripoli, Giada, Gayer-Anderson, Charlotte, Freeman, Tom P, Johnson, Emma C, Jongsma, Hannah E, Stilo, Simona, La Cascia, Caterina, Ferraro, Laura, La Barbera, Daniele, Lasalvia, Antonio, Tosato, Sarah, Tarricone, Ilaria, D'Andrea, Giuseppe, Galatolo, Michela, and Tortelli, Andrea

Subjects
*CANNABIS (Genus), *CONFIDENCE intervals, *PSYCHOSES, *CASE-control method, *RISK assessment, *AFFECTIVE disorders, *CHI-squared test, *DESCRIPTIVE statistics, *LOGISTIC regression analysis
Abstract

Background: While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis. Methods: We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case–control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC. We ran logistic regressions to examine whether RFUC were associated with first-episode psychosis (FEP) case–control status. Path analysis then examined the relationship between RFUC, subsequent patterns of cannabis use, and case–control status. Results: Controls (86.1%) and FEPp (75.63%) were most likely to report 'because of friends' as their most common RFUC. However, 20.1% of FEPp compared to 5.8% of controls reported: 'to feel better' as their RFUC (χ2 = 50.97; p < 0.001). RFUC 'to feel better' was associated with being a FEPp (OR 1.74; 95% CI 1.03–2.95) while RFUC 'with friends' was associated with being a control (OR 0.56; 95% CI 0.37–0.83). The path model indicated an association between RFUC 'to feel better' with heavy cannabis use and with FEPp-control status. Conclusions: Both FEPp and controls usually started using cannabis with their friends, but more patients than controls had begun to use 'to feel better'. People who reported their reason for first using cannabis to 'feel better' were more likely to progress to heavy use and develop a psychotic disorder than those reporting 'because of friends'. [ABSTRACT FROM AUTHOR]

Published
2023
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30. Cannabis use as a potential mediator between childhood adversity and first-episode psychosis: results from the EU-GEI case–control study.

Author

Trotta, Giulia, Rodriguez, Victoria, Quattrone, Diego, Spinazzola, Edoardo, Tripoli, Giada, Gayer-Anderson, Charlotte, Freeman, Tom P, Jongsma, Hannah E, Sideli, Lucia, Aas, Monica, Stilo, Simona A, La Cascia, Caterina, Ferraro, Laura, La Barbera, Daniele, Lasalvia, Antonio, Tosato, Sarah, Tarricone, Ilaria, D'Andrea, Giuseppe, Tortelli, Andrea, and Schürhoff, Franck

Subjects
SUBSTANCE abuse prevention, ADVERSE childhood experiences, CANNABIS (Genus), SUBSTANCE abuse, PSYCHOSES, CASE-control method, QUESTIONNAIRES, RESEARCH funding, PSYCHOTHERAPY
Abstract

Background: Childhood adversity and cannabis use are considered independent risk factors for psychosis, but whether different patterns of cannabis use may be acting as mediator between adversity and psychotic disorders has not yet been explored. The aim of this study is to examine whether cannabis use mediates the relationship between childhood adversity and psychosis. Methods: Data were utilised on 881 first-episode psychosis patients and 1231 controls from the European network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Detailed history of cannabis use was collected with the Cannabis Experience Questionnaire. The Childhood Experience of Care and Abuse Questionnaire was used to assess exposure to household discord, sexual, physical or emotional abuse and bullying in two periods: early (0–11 years), and late (12–17 years). A path decomposition method was used to analyse whether the association between childhood adversity and psychosis was mediated by (1) lifetime cannabis use, (2) cannabis potency and (3) frequency of use. Results: The association between household discord and psychosis was partially mediated by lifetime use of cannabis (indirect effect coef. 0.078, s.e. 0.022, 17%), its potency (indirect effect coef. 0.059, s.e. 0.018, 14%) and by frequency (indirect effect coef. 0.117, s.e. 0.038, 29%). Similar findings were obtained when analyses were restricted to early exposure to household discord. Conclusions: Harmful patterns of cannabis use mediated the association between specific childhood adversities, like household discord, with later psychosis. Children exposed to particularly challenging environments in their household could benefit from psychosocial interventions aimed at preventing cannabis misuse. [ABSTRACT FROM AUTHOR]

Published
2023
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31. Child maltreatment, migration and risk of first-episode psychosis: results from the multinational EU-GEI study.

Author

D'Andrea, Giuseppe, Lal, Jatin, Tosato, Sarah, Gayer-Anderson, Charlotte, Jongsma, Hannah E., Stilo, Simona A., van der Ven, Els, Quattrone, Diego, Velthorst, Eva, Berardi, Domenico, Rossi Menezes, Paulo, Arango, Celso, Parellada, Mara, Lasalvia, Antonio, La Cascia, Caterina, Ferraro, Laura, La Barbera, Daniele, Sideli, Lucia, Bobes, Julio, and Bernardo, Miguel

Subjects
POPULATION, CHILD abuse, PSYCHOSES, PSYCHOLOGICAL vulnerability, MIGRANT labor, RISK assessment, PSYCHOSOCIAL factors, CHI-squared test, QUESTIONNAIRES, RESEARCH funding, LOGISTIC regression analysis
Abstract

Background: Child maltreatment (CM) and migrant status are independently associated with psychosis. We examined prevalence of CM by migrant status and tested whether migrant status moderated the association between CM and first-episode psychosis (FEP). We further explored whether differences in CM exposure contributed to variations in the incidence rates of FEP by migrant status. Methods: We included FEP patients aged 18–64 years in 14 European sites and recruited controls representative of the local populations. Migrant status was operationalized according to generation (first/further) and region of origin (Western/non-Western countries). The reference population was composed by individuals of host country's ethnicity. CM was assessed with Childhood Trauma Questionnaire. Prevalence ratios of CM were estimated using Poisson regression. We examined the moderation effect of migrant status on the odds of FEP by CM fitting adjusted logistic regressions with interaction terms. Finally, we calculated the population attributable fractions (PAFs) for CM by migrant status. Results: We examined 849 FEP cases and 1142 controls. CM prevalence was higher among migrants, their descendants and migrants of non-Western heritage. Migrant status, classified by generation (likelihood test ratio:χ2 = 11.3, p = 0.004) or by region of origin (likelihood test ratio:χ2 = 11.4, p = 0.003), attenuated the association between CM and FEP. PAFs for CM were higher among all migrant groups compared with the reference populations. Conclusions: The higher exposure to CM, despite a smaller effect on the odds of FEP, accounted for a greater proportion of incident FEP cases among migrants. Policies aimed at reducing CM should consider the increased vulnerability of specific subpopulations. [ABSTRACT FROM AUTHOR]

Published
2023
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32. Differences in Patterns of Stimulant Use and Their Impact on First-Episode Psychosis Incidence: An Analysis of the EUGEI Study.

Author

Rodríguez-Toscano, Elisa, Alloza, Clara, Fraguas, David, Durán-Cutilla, Manuel, Roldán, Laura, Sánchez-Gutiérrez, Teresa, López-Montoya, Gonzalo, Parellada, Mara, Moreno, Carmen, Gayer-Anderson, Charlotte, Jongsma, Hannah E, Forti, Marta Di, Quattrone, Diego, Velthorst, Eva, Haan, Lieuwe de, Selten, Jean-Paul, Szöke, Andrei, Llorca, Pierre-Michel, Tortelli, Andrea, and Bobes, Julio

Subjects
CENTRAL nervous system stimulants, CANNABIS (Genus), CONFIDENCE intervals, PSYCHOSES, AGE distribution, DISEASE incidence, SEX distribution, AMPHETAMINES, METHAMPHETAMINE, RESEARCH funding, DISEASE prevalence, DESCRIPTIVE statistics, DRUGS of abuse, LOGISTIC regression analysis, ODDS ratio, MENTAL health services, EDUCATIONAL attainment
Abstract

Background Use of illegal stimulants is associated with an increased risk of psychotic disorder. However, the impact of stimulant use on odds of first-episode psychosis (FEP) remains unclear. Here, we aimed to describe the patterns of stimulant use and examine their impact on odds of FEP. Methods We included patients with FEP aged 18–64 years who attended psychiatric services at 17 sites across 5 European countries and Brazil, and recruited controls representative of each local population (FEP = 1130; controls = 1497). Patterns of stimulant use were described. We computed fully adjusted logistic regression models (controlling for age, sex, ethnicity, cannabis use, and education level) to estimate their association with odds of FEP. Assuming causality, we calculated the population-attributable fractions for stimulant use associated with the odds for FEP. Findings Prevalence of lifetime and recent stimulant use in the FEP sample were 14.50% and 7.88% and in controls 10.80% and 3.8%, respectively. Recent and lifetime stimulant use was associated with increased odds of FEP compared with abstainers [fully adjusted odds ratio 1.74,95% confidence interval (CI) 1.20–2.54, P =.004 and 1.62, 95% CI 1.25–2.09, P <.001, respectively]. According to PAFs, a substantial number of FEP cases (3.35% [95% CI 1.31–4.78] for recent use and 7.61% [95% CI 3.68–10.54] for lifetime use) could have been prevented if stimulants were no longer available and the odds of FEP and PAFs for lifetime and recent stimulant use varied across countries. Interpretation Illegal stimulant use has a significant and clinically relevant influence on FEP incidence, with varying impacts across countries. [ABSTRACT FROM AUTHOR]

Published
2023
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38. Use of multiple polygenic risk scores for distinguishing schizophrenia-spectrum disorder and affective psychosis categories in a first-episode sample; the EU-GEI study.

Author

Rodriguez, Victoria, Alameda, Luis, Quattrone, Diego, Tripoli, Giada, Gayer-Anderson, Charlotte, Spinazzola, Edoardo, Trotta, Giulia, Jongsma, Hannah E., Stilo, Simona, La Cascia, Caterina, Ferraro, Laura, La Barbera, Daniele, Lasalvia, Antonio, Tosato, Sarah, Tarricone, Ilaria, Bonora, Elena, Jamain, Stéphane, Selten, Jean-Paul, Velthorst, Eva, and de Haan, Lieuwe

Subjects
GENETICS, CONFIDENCE intervals, SCHIZOPHRENIA, PSYCHOSES, MULTIPLE regression analysis, RISK assessment, AFFECTIVE disorders, DISEASE susceptibility, GENOTYPES, ODDS ratio, PREDICTION models
Abstract

Background: Schizophrenia (SZ), bipolar disorder (BD) and depression (D) run in families. This susceptibility is partly due to hundreds or thousands of common genetic variants, each conferring a fractional risk. The cumulative effects of the associated variants can be summarised as a polygenic risk score (PRS). Using data from the EUropean Network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) first episode case–control study, we aimed to test whether PRSs for three major psychiatric disorders (SZ, BD, D) and for intelligent quotient (IQ) as a neurodevelopmental proxy, can discriminate affective psychosis (AP) from schizophrenia-spectrum disorder (SSD). Methods: Participants (842 cases, 1284 controls) from 16 European EU-GEI sites were successfully genotyped following standard quality control procedures. The sample was stratified based on genomic ancestry and analyses were done only on the subsample representing the European population (573 cases, 1005 controls). Using PRS for SZ, BD, D, and IQ built from the latest available summary statistics, we performed simple or multinomial logistic regression models adjusted for 10 principal components for the different clinical comparisons. Results: In case–control comparisons PRS-SZ, PRS-BD and PRS-D distributed differentially across psychotic subcategories. In case–case comparisons, both PRS-SZ [odds ratio (OR) = 0.7, 95% confidence interval (CI) 0.54–0.92] and PRS-D (OR = 1.31, 95% CI 1.06–1.61) differentiated AP from SSD; and within AP categories, only PRS-SZ differentiated BD from psychotic depression (OR = 2.14, 95% CI 1.23–3.74). Conclusions: Combining PRS for severe psychiatric disorders in prediction models for psychosis phenotypes can increase discriminative ability and improve our understanding of these phenotypes. Our results point towards the potential usefulness of PRSs in specific populations such as high-risk or early psychosis phases. [ABSTRACT FROM AUTHOR]

Published
2023
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39. Child maltreatment, migration and risk of first-episode psychosis: results from the multinational EU-GEI study

Author

D'Andrea, Giuseppe, primary, Lal, Jatin, additional, Tosato, Sarah, additional, Gayer-Anderson, Charlotte, additional, Jongsma, Hannah E., additional, Stilo, Simona A., additional, van der Ven, Els, additional, Quattrone, Diego, additional, Velthorst, Eva, additional, Berardi, Domenico, additional, Rossi Menezes, Paulo, additional, Arango, Celso, additional, Parellada, Mara, additional, Lasalvia, Antonio, additional, La Cascia, Caterina, additional, Ferraro, Laura, additional, La Barbera, Daniele, additional, Sideli, Lucia, additional, Bobes, Julio, additional, Bernardo, Miguel, additional, Sanjuán, Julio, additional, Santos, Jose Luis, additional, Arrojo, Manuel, additional, Del-Ben, Cristina Marta, additional, Tripoli, Giada, additional, Llorca, Pierre-Michel, additional, de Haan, Lieuwe, additional, Selten, Jean-Paul, additional, Tortelli, Andrea, additional, Szöke, Andrei, additional, Muratori, Roberto, additional, Rutten, Bart P., additional, van Os, Jim, additional, Jones, Peter B., additional, Kirkbride, James B., additional, Murray, Robin M., additional, di Forti, Marta, additional, Tarricone, Ilaria, additional, and Morgan, Craig, additional

Published
2022
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40. Exploring the mediation of DNA methylation across the epigenome between childhood adversity and First Episode of Psychosis – findings from the EU-GEI study

Author

Luis Alameda, Zhonghua Liu, Pak Sham, AAS Monica, Trotta Giulia, Rodriguez Victoria, Marta di Forti, Stilo Simona, Kandaswamy Radhika, Celso Arango, Manuel Arrojo, Miquel Bernardo, Julio Bobes, Lieuwe de Haan, Cristina Del-Ben, Charlotte Gayer-Anderson, Sideli Lucia, Peter Jones, Hannah Jongsma, James Kirkbride, Caterina La Cascia, Antonio Lasalvia, Sarah Tosato, Pierre Michel Llorca, Paulo Menezes, Jim van Os, Quattrone Diego, Bart Rutten, José Santos, Julio Sanjuan, Jean-Paul Selten, Andrei Szöke, Ilaria Tarricone, Andrea Tortelli, Eva Velthorst, Craig Morgan, Emma Dempster, Eilis Hannon, Joe Burrage, Jonathan Mill, Robin Murray, and Chloe Wong

Abstract

Studies conducted in psychotic disorders have shown that DNA-methylation (DNAm) is sensitive to the impact of Childhood Adversity (CA). However, whether it mediates the association between CA and psychosis is yet to be explored. Epigenome-wide association studies (EWAS) using the Illumina Infinium-Methylation EPIC array in peripheral blood tissue from 366 First-episode of psychosis and 517 healthy controls was performed. Polyvictimization scores were created for abuse, neglect, and composite adversity with the Childhood Trauma Questionnaire (CTQ). Regressions examining (I) CTQ scores with psychosis; (II) with DNAm EWAS level and (III), then between DNAm and caseness, adjusted for a variety of confounders were conducted. Divide-Aggregate Composite-null Test for the composite null hypothesis of no mediation effect was conducted. Enrichment analyses were conducted with missMethyl package and the KEGG database. Our results show that CA was associated with psychosis (Composite: OR = 3.09; p =

Published
2022

41. Childhood Maltreatment, Educational Attainment, and IQ: Findings From a Multicentric Case-control Study of First-episode Psychosis (EU-GEI)

Author

Sideli, Lucia, Schimmenti, Adriano, La Barbera, Daniele, La Cascia, Caterina, Ferraro, Laura, Aas, Monica, Alameda, Luis, Velthorst, Eva, Fisher, Helen L, Caretti, Vincenzo, Trotta, Giulia, Tripoli, Giada, Quattrone, Diego, Gayer-Anderson, Charlotte, Seminerio, Fabio, Sartorio, Crocettarachele, Marrazzo, Giovanna, Lasalvia, Antonio, Tosato, Sarah, Tarricone, Ilaria, Berardi, Domenico, D'Andrea, Giuseppe, Arango, Celso, Arrojo, Manuel, Bernardo, Miguel, Bobes, Julio, Sanjuán, Julio, Santos, Jose Luis, Menezes, Paulo Rossi, Del-Ben, Cristina Marta, Jongsma, Hannah E, Jones, Peter B, Kirkbride, James B, Llorca, Pierre-Michel, Tortelli, Andrea, Pignon, Baptiste, de Haan, Lieuwe, Selten, Jean-Paul, Van Os, Jim, Rutten, Bart P, Di Forti, Marta, Morgan, Craig, Murray, Robin M, EU-GEI WP2 Group, Sideli, Lucia, Schimmenti, Adriano, La Barbera, Daniele, La Cascia, Caterina, Ferraro, Laura, Aas, Monica, Alameda, Lui, Velthorst, Eva, Fisher, Helen L, Caretti, Vincenzo, Trotta, Giulia, Tripoli, Giada, Quattrone, Diego, Gayer-Anderson, Charlotte, Seminerio, Fabio, Sartorio, Crocettarachele, Marrazzo, Giovanna, Lasalvia, Antonio, Tosato, Sarah, Tarricone, Ilaria, Berardi, Domenico, D'Andrea, Giuseppe, Arango, Celso, Arrojo, Manuel, Bernardo, Miguel, Bobes, Julio, Sanjuán, Julio, Santos, Jose Lui, Menezes, Paulo Rossi, Del-Ben, Cristina Marta, Jongsma, Hannah E, Jones, Peter B, Kirkbride, James B, Llorca, Pierre-Michel, Tortelli, Andrea, Pignon, Baptiste, de Haan, Lieuwe, Selten, Jean-Paul, Van Os, Jim, Rutten, Bart P, Di Forti, Marta, Morgan, Craig, Murray, Robin M, Adult Psychiatry, APH - Mental Health, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, European Commission, Fundação de Amparo à Pesquisa do Estado de São Paulo, Dutch Research Council, Economic and Social Research Council (UK), Kings College London, Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III, Comunidad de Madrid, Fundación Alicia Koplowitz, Fundación Alonso Lozano, NIHR Biomedical Research Centre (UK), Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, MUMC+: MA Psychiatrie (3), and RS: MHeNs - R3 - Neuroscience

Subjects
Affective Disorders, Psychotic, Intelligence Tests, STRESS, childhood abuse, BIPOLAR DISORDER, ASSOCIATION, schizophrenia, Psychiatry and Mental health, Psychotic Disorders, IQ, ADVERSITIES, Case-Control Studies, ONSET, RELIABILITY, PHYSICAL ABUSE, Humans, childhood neglect, psychosis, Child Abuse, VALIDITY, Child, Regular Articles, TRAUMA
Abstract

[Background and hypothesis] Evidence suggests that childhood maltreatment (ie, childhood abuse and childhood neglect) affects educational attainment and cognition. However, the association between childhood maltreatment and Intelligence Quotient (IQ) seems stronger among controls compared to people with psychosis. We hypothesised that: the association between childhood maltreatment and poor cognition would be stronger among community controls than among people with first-episode of psychosis (FEP); compared to abuse, neglect would show stronger associations with educational attainment and cognition; the association between childhood maltreatment and IQ would be partially accounted for by other risk factors; and the association between childhood maltreatment, educational attainment, and IQ would be stronger among patients with affective psychoses compared to those with nonaffective psychoses., [Study Design] 829 patients with FEP and 1283 community controls from 16 EU-GEI sites were assessed for child maltreatment, education attainment, and IQ., [Study Results] In both the FEP and control group, childhood maltreatment was associated with lower educational attainment. The association between childhood maltreatment and lower IQ was robust to adjustment for confounders only among controls. Whereas childhood neglect was consistently associated with lower attainment and IQ in both groups, childhood abuse was associated with IQ only in controls. Among both patients with affective and nonaffective psychoses, negative associations between childhood maltreatment and educational attainment were observed, but the crude association with IQ was only evident in affective psychoses., [Conclusions] Our findings underscore the role of childhood maltreatment in shaping academic outcomes and cognition of people with FEP as well as controls., The EU-GEI Study is funded by grant agreement HEALTH-F2-2010-241909 (Project EU-GEI) from the European Community’s Seventh Framework Programme, and Grant 2012/0417-0 from the São Paulo Research Foundation. B.P.F. Rutten is funded by a VIDI award (no. 91.718.336) from the Netherlands Scientific Organization. H. L. Fisher, C. Gayer-Anderson, and C. Morgan are supported by the Economic and Social Research Council (ESRC) Centre for Society and Mental Health at King’s College London [ES/S012567/1]. C. Arango has received support by the Spanish Ministry of Science and Innovation. Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/024), co-financed by ERDF Funds from the European Commission, “A way of making Europe”, CIBERSAM. Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds. European Union Seventh Framework Program under grant agreements, FP7- HEALTH-2013-2.2.1-2-603196 (Project PSYSCAN) and FP7- HEALTH-2013-2.2.1-2-602478 (Project METSY); and European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No 115916, Project PRISM, and grant agreement No 777394, Project AIMS-2-TRIALS), Fundación Familia Alonso and Fundación Alicia Koplowitz. J.B. Kirkbride is supported by the NIHR University College London Hospital Biomedical Research Centre.

Published
2022

43. The EUropean Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI)

Author

Gayer-Anderson, Charlotte, Jongsma, Hannah E., Di Forti, Marta, Quattrone, Diego, Velthorst, Eva, De Haan, Lieuwe, Selten, Jean-Paul, Szöke, Andrei, Llorca, Pierre-Michel, Tortelli, Andrea, Arango, Celso, Bobes, Julio, Bernardo, Miguel, Sanjuán, Julio, Santos, José Luis, Arrojo, Manuel, Parellada, Mara, Tarricone, Ilaria, Berardi, Domenico, Ruggeri, Mirella, Lasalvia, Antonio, Ferraro, Laura, La Cascia, Caterina, La Barbera, Daniele, Menezes, Paulo Rossi, Del-Ben, Cristina Marta, Rutten, Bart P., Van Os, Jim, Jones, Peter B., Murray, Robin M., Kirkbride, James B., Morgan, Craig, Hubbard, Kathryn, Beards, Stephanie, Reininghaus, Ulrich, Tripoli, Giada, Stilo, Simona A., Roldán, Laura, López, Gonzalo, Matteis, Mario, Rapado, Marta, González, Emiliano, Martínez, Covadonga, Cuadrado, Pedro, Solano, José Juan Rodríguez, Carracedo, Angel, Costas, Javier, Bernardo, Enrique García, Sánchez, Emilio, Olmeda, Ma Soledad, Cabrera, Bibiana, Lorente-Rovira, Esther, Garcia-Portilla, Paz, Jiménez-López, Estela, Franke, Nathalie, Van Dam, Daniella, Termorshuizen, Fabian, Van Der Ven, Elsje, Messchaart, Elles, Leboyer, Marion, Schürhoff, Franck, Baudin, Grégoire, Ferchiou, Aziz, Pignon, Baptiste, Jamain, Stéphane, Richard, Jean-Romain, Charpeaud, Thomas, Tronche, Anne-Marie, Frijda, Flora, Sideli, Lucia, Seminerio, Fabio, Sartorio, Crocettarachele, Marrazzo, Giovanna, Loureiro, Camila Marcelino, Shuhama, Rosana, Tosato, Sarah, Bonetto, Chiara, Cristofalo, Doriana, Gayer-Anderson, Charlotte [0000-0003-1636-889X], Apollo - University of Cambridge Repository, Gayer-Anderson C., Jongsma H.E., Di Forti M., Quattrone D., Velthorst E., de Haan L., Selten J.-P., Szoke A., Llorca P.-M., Tortelli A., Arango C., Bobes J., Bernardo M., Sanjuan J., Santos J.L., Arrojo M., Parellada M., Tarricone I., Berardi D., Ruggeri M., Lasalvia A., Ferraro L., La Cascia C., La Barbera D., Menezes P.R., Del-Ben C.M., Hubbard K., Beards S., Reininghaus U., Tripoli G., Stilo S.A., Roldan L., Lopez G., Matteis M., Rapado M., Gonzalez E., Martinez C., Cuadrado P., Solano J.J.R., Carracedo A., Costas J., Bernardo E.G., Sanchez E., Olmeda M.S., Cabrera B., Lorente-Rovira E., Garcia-Portilla P., Jimenez-Lopez E., Franke N., van Dam D., Termorshuizen F., van der Ven E., Messchaart E., Leboyer M., Schurhoff F., Baudin G., Ferchiou A., Pignon B., Jamain S., Richard J.-R., Charpeaud T., Tronche A.-M., Frijda F., Sideli L., Seminerio F., Sartorio C., Marrazzo G., Loureiro C.M., Shuhama R., Tosato S., Bonetto C., Cristofalo D., Rutten B.P., van Os J., Jones P.B., Murray R.M., Kirkbride J.B., Morgan C., Gayer-Anderson, Charlotte, Jongsma, Hannah E., Di Forti, Marta, Quattrone, Diego, Velthorst, Eva, de Haan, Lieuwe, Selten, Jean-Paul, Szöke, Andrei, Llorca, Pierre-Michel, Tortelli, Andrea, Arango, Celso, Bobes, Julio, Bernardo, Miguel, Sanjuán, Julio, Santos, José Lui, Arrojo, Manuel, Parellada, Mara, Tarricone, Ilaria, Berardi, Domenico, Ruggeri, Mirella, Lasalvia, Antonio, Ferraro, Laura, La Cascia, Caterina, La Barbera, Daniele, Menezes, Paulo Rossi, Del-Ben, Cristina Marta, Rutten, Bart P., van Os, Jim, Jones, Peter B., Murray, Robin M., Kirkbride, James B., Morgan, Craig, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, MUMC+: MA Psychiatrie (3), RS: MHeNs - R3 - Neuroscience, MUMC+: Hersen en Zenuw Centrum (3), ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Adult Psychiatry, and APH - Mental Health

Subjects
Male, Health (social science), Epidemiology, Ethnic group, Ethnic Group, Gene-environment interactions, Environment–environment interactions, 0302 clinical medicine, Ethnicity, 10. No inequality, First episode, RISK, biology, Incidence (epidemiology), Incidence, CANNABIS, Middle Aged, Case-control, First-episode psychosis, 3. Good health, Europe, Psychiatry and Mental health, Case–control Environment–environment interactions EU-GEI First-episode psychosis Gene–environment interactions Incidence, Case–control, EU-GEI, Gene–environment interactions, Schizophrenia, Cohort, Female, Psychology, Case-Control Studie, Brazil, Human, Adult, medicine.medical_specialty, Social Psychology, Adolescent, Study Protocols and Samples, DISORDERS, Environment–environment interaction, Representativeness heuristic, 03 medical and health sciences, Young Adult, PSYCHOSIS, AGE, First-episode psychosi, Environment-environment interactions, medicine, Humans, Gene–environment interaction, Settore MED/25 - Psichiatria, METAANALYSIS, biology.organism_classification, medicine.disease, 030227 psychiatry, Case-Control Studies, Gene-Environment Interaction, Cannabis, CHILDHOOD ADVERSITIES, 030217 neurology & neurosurgery, Demography
Abstract

Funder: FP7 Ideas: European Research Council; doi: http://dx.doi.org/10.13039/100011199; Grant(s): HEALTH-F2-2010-241909, Purpose: The EUropean Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI) study contains an unparalleled wealth of comprehensive data that allows for testing hypotheses about (1) variations in incidence within and between countries, including by urbanicity and minority ethnic groups; and (2) the role of multiple environmental and genetic risk factors, and their interactions, in the development of psychotic disorders. Methods: Between 2010 and 2015, we identified 2774 incident cases of psychotic disorders during 12.9 million person-years at risk, across 17 sites in 6 countries (UK, The Netherlands, France, Spain, Italy, and Brazil). Of the 2774 incident cases, 1130 cases were assessed in detail and form the case sample for case–control analyses. Across all sites, 1497 controls were recruited and assessed. We collected data on an extensive range of exposures and outcomes, including demographic, clinical (e.g. premorbid adjustment), social (e.g. childhood and adult adversity, cannabis use, migration, discrimination), cognitive (e.g. IQ, facial affect processing, attributional biases), and biological (DNA via blood sample/cheek swab). We describe the methodology of the study and some descriptive results, including representativeness of the cohort. Conclusions: This resource constitutes the largest and most extensive incidence and case–control study of psychosis ever conducted.

Published
2020

44. Treated Incidence of Psychotic Disorders in the Multinational EU-GEI Study

Author

Jongsma, Hannah E., Gayer-Anderson, Charlotte, Lasalvia, Antonio, Quattrone, Diego, Mulè, Alice, Szöke, Andrei, Selten, Jean-Paul, Turner, Caitlin, Arango, Celso, Tarricone, Ilaria, Berardi, Domenico, Tortelli, Andrea, Llorca, Pierre-Michel, de Haan, Lieuwe, Bobes, Julio, Bernardo, Miguel, Sanjuán, Julio, Santos, José Luis, Arrojo, Manuel, Del-Ben, Cristina Marta, Menezes, Paulo Rossi, Murray, Robin M., Rutten, Bart P., Jones, Peter B., van Os, Jim, Morgan, Craig, and Kirkbride, James B.

Published
2018
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45. Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: the EU-GEI study.

Author

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

Subjects
SCHIZOPHRENIA risk factors, CONFIDENCE intervals, PSYCHOSES, CASE-control method, RISK assessment, RESEARCH funding, QUESTIONNAIRES, DESCRIPTIVE statistics, ODDS ratio, CHILDREN
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. [ABSTRACT FROM AUTHOR]

Published
2023
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47. Mapping genomic loci prioritises genes and implicates synaptic biology in schizophrenia

Author

Trubetskoy, Vassily, Pardinas, Antonio, Qi, Ting, Panagiotaropoulou, Georgia, Awasthi, Swapnil, Bigdeli, Tim B., Bryois, Julien, Chen, Chia-Yen, Dennison, Charlotte A., Hall, Lynsey, Lam, Max, Watanabe, Kyoto, Frei, Oleksandr, Ge, Tian, Harwood, Janet C., Koopmans, Frank, Magnusson, Sigurdur, Richards, Alexander L., Sidorenko, Julia, Wu, Yang, Zeng, Jian, Grove, Jakob, Kim, Minsoo, Li, Zhiqiang, Voloudakis, Georgios, Zhang, Wen, Adams, Mark, Agartz, Ingrid, Atkinson, Elizabeth G., Agerbo, Esben, Al Eissa, Mariam, Albus, Margot, Alexander, Madeline, Alizadeh, Behrooz Z., Alptekin, Köksal, Als, Thomas D., Amin, Farooq, Arolt, Volker, Arrojo, Manuel, Athanasiu, Lavinia, Azevedo, Maria Helena, Bacanu, Silviu A., Bass, Nicholas J., Begemann, Martin, Belliveau, Richard A., Bene, Judit, Benyamin, Beben, Bergen, Sarah E., Blasi, Giuseppe, Bobes, Julio, Bonassi, Stefano, Braun, Alice, Affonseca Bressan, Rodrigo, Bromet, Evelyn J., Bruggeman, Richard, Buckley, Peter F., Buckner, Randy L., Bybjerg-Grauholm, Jonas, Cahn, Wiepke, Cairns, Murray J., Calkins, Monica E., Carr, Vaughan J., Castle, David, Catts, Stanley V., Chambert, Kimberley D., Chan, Raymond C. K., Chaumette, Boris, Cheng, Wei, Cheung, Eric F. C., Chong, Siow Ann, Cohen, David, Consoli, Angele, Cordeiro, Quirino, Costas, Javier, Curtis, Charles, Davidson, Michael, Davis, Kenneth L., De Haan, Lieuwe, Degenhardt, Franziska, DeLisi, Lynn E., Demontis, Ditte, Dickerson, Faith, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Duan, Jubao, Ducci, Giuseppe, Dudbridge, Frank, Eriksson, Johan G., Fananas, Lourdes, Faraone, Stephen V., Fiorentino, Alessia, Forstner, Andreas, Frank, Josef, Freimer, Nelson B., Fromer, Menachem, Frustaci, Alessandra, Gadelha, Ary, Genovese, Giulio, Gershon, Elliot S., Giannitelli, Marianna, Giegling, Ina, Giusti-Rodríguez, Paola, Godard, Stephanie, Goldstein, Jacqueline I., González Peñas, Javier, González-Pinto, Ana, Gopa, Srihari, Gratten, Jacob, Green, Michael F., Greenwood, Tiffany A., Guillin, Olivier, Gülöksüz, Sinan, Gur, Raquel E., Gur, Ruben C., Gutiérrez, Blanca, Hahn, Eric, Hakonarson, Hakon, Haroutunian, Vahram, Hartmann, Annette M., Harvey, Carol, Hayward, Caroline, Henskens, Frans A., Herms, Stefan, Hoffmann, Per, Howrigan, Daniel P., Ikeda, Masashi, Iyegbe, Conrad, Joa, Inge, Julià, Antonio, Kähler, Anna K., Kam-Thong, Tony, Kamatani, Yoichiro, Karachanak-Yankova, Sena, Kebir, Oussama, Keller, Matthew C., Kelly, Brian J., Khrunin, Andrey, Kim, Sung-Wan, Klovins, Janis, Kondratiev, Nikolay, Konte, Bettina, Kraft, Julia, Kubo, Michiaki, Kučinskas, Vaidutis, Ausrele Kučinskiene, Zita, Kusumawardhani, Agung, Kuzelov a-Ptackova, Hana, Land, Stefano, Lazzeroni, Laura C., Lee, Phil H., Legge, Sophie E., Lehrer, Douglas S., Lencer, Rebecca, Lerer, Bernard, Li, Miaoxin, Lieberman, Jeffrey, Light, Gregory A., Limborska, Svetlana, Liu, Chih-Min, Lönnqvist, Jouko, Loughland, Carmel M., Lubiski, Jan, Luykx, Jurjen J., Lynham, Amy, Macel Jr., Milan, Mackinnon, Andrew, Magnusson, Patrik K. E., Maher, Brion S., Maier, Wolfgang, Malaspina, Dolores, Mallet, Jacques, Marder, Stephen R., Marsal, Sara, Martin, Alicia R., Martorell, Lourdes, Mattheisen, Manuel, McCarley, Robert W., McDonald, Colm, McGrath, John J., Medeiros, Helena, Meier, Sandra, Melegh, Bela, Melle, Ingrid, Mesholam-Gately, Raquelle I., Metspalu, Andres, Michie, Patricia T., Milani, Lili, Milanova, Vihara, Mitjans, Marina, Molden, Espen, Molina, Esther, Molto, María Dolores, Mondelli, Valeria, Moreno, Carmen, Morley, Christopher P., Muntané, Gerard, Murphy, Kieran C., Myin-Germeys, Inez, Nenadić, Igor, Nestadt, Gerald, Nikitina-Zake, Liene, Noto, Cristiano, Neuchterlein, Keith H., O'Brien, Niamh Louise, O'Neill, F. Anthony., Oh, Sang-Yun, Olincy, Ann, Ota, Vanessa Kiyomi, Pantelis, Christos, Papadimitrou, George N., Paredella, Mara, Paurio, Tiina, Pellegrino, Renata, Periyasamy, Sathish, Perkins, Diana O., Pfuhlmann, Bruno, Pietilainen, Olli, Pimm, Jonathan, Porteous, David, Powell, John, Quattrone, Diego, Quested, Digby, Radant, Allen D., Rampino, Antonio, Rapaport, Mark H., Rautanen, Anna, Reichenberg, Abraham, Roe, Cheryl, Roffman, Joshua L., Roth, Julian, Rothermundt, Matthias, Rutten, Bart P. F., Saker-Delye, Safaa, Salomaa, Veiko, Sanjuan, Julio, Santoro, Marcos Leite, Savitz, Adam, Schall, Ulrich, Scott, Rodney J., Seidman, Larry J., Sharp, Sally Isabel, Shi, Jianxin, Sigurdsson, Engilbert, Sim, Kang, Skarabis, Nora, Slominsky, Petr, So, Hon-Cheong, Sobell, Janet L., Soderman, Erik, Stain, Helen J., Steen, Nils Eiel, Steixner-Kumar, Agnes, Stogmann, Elisabeth, Stone, William S., Straub, Richard E., Streit, Fabian, Stregman, Eric, Stroup, T. Scott, Subramaniam, Mythily, Sugar, Catherine A., Suvisaari, Jaana, Svrakic, Dragan M., Swerdlow, Neal R., Szatkiewicz, Jin P., Ta, Thi Minh Tam, and Takahashi, Atsushi

Abstract

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies.

Published
2022

49. 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

Author

Quattrone, Diego, Reininghaus, Ulrich, Richards, Alex L., Tripoli, Giada, Ferraro, Laura, Quattrone, Andrea, Marino, Paolo, Rodriguez, Victoria, Spinazzola, Edoardo, Gayer-Anderson, Charlotte, Jongsma, Hannah E., Jones, Peter B., La Cascia, Caterina, La Barbera, Daniele, Tarricone, Ilaria, Bonora, Elena, Tosato, Sarah, Lasalvia, Antonio, Szöke, Andrei, Arango, Celso, Bernardo, Miquel, Bobes, Julio, Del Ben, Cristina Marta, Menezes, Paulo Rossi, Llorca, Pierre-Michel, Santos, Jose Luis, Sanjuán, Julio, Arrojo, Manuel, Tortelli, Andrea, Velthorst, Eva, Berendsen, Steven, De Haan, Lieuwe, Rutten, Bart P. F., Lynskey, Michael T., Freeman, Tom P., Kirkbride, James B., Sham, Pak C., O’Donovan, Michael C., Cardno, Alastair G., Vassos, Evangelos, Van Os, Jim, Morgan, Craig, Murray, Robin M., Lewis, Cathryn M., Di Forti, Marta, Hubbard, Kathryn, Beards, Stephanie, Stilo, Simona A., Parellada, Mara, Fraguas, David, Castro, Marta Rapado, Andreu-Bernabeu, Álvaro, López, Gonzalo, Matteis, Mario, González, Emiliano, Durán-Cutilla, Manuel, Díaz-Caneja, Covadonga M., Cuadrado, Pedro, Rodríguez Solano, José Juan, Carracedo, Angel, Costas, Javier, Sánchez, Emilio, Amoretti, Silvia, Lorente-Rovira, Esther, Garcia-Portilla, Paz, Jiménez-López, Estela, Franke, Nathalie, Van Dam, Daniella, Termorshuizen, Fabian, Van Der Ven, Elsje, Messchaart, Elles, Leboyer, Marion, Schürhoff, Franck, Jamain, Stéphane, Baudin, Grégoire, Ferchiou, Aziz, Pignon, Baptiste, Richard, Jean-Romain, Charpeaud, Thomas, Tronche, Anne-Marie, Frijda, Flora, Marrazzo, Giovanna, Sideli, Lucia, Sartorio, Crocettarachele, Seminerio, Fabio, Loureiro, Camila Marcelino, Shuhama, Rosana, Ruggeri, Mirella, Bonetto, Chiara, Cristofalo, Doriana, Berardi, Domenico, Seri, Marco, D’Andrea, Giuseppe, Quattrone, Diego [0000-0002-6051-8309], Richards, Alex L. [0000-0003-3218-7247], Marino, Paolo [0000-0003-3571-1753], Rodriguez, Victoria [0000-0003-0383-0846], Jones, Peter B. [0000-0002-0387-880X], Tosato, Sarah [0000-0002-9665-7538], Bernardo, Miquel [0000-0001-8748-6717], Bobes, Julio [0000-0003-2187-4033], Del Ben, Cristina Marta [0000-0003-0145-9975], Menezes, Paulo Rossi [0000-0001-6330-3314], Llorca, Pierre-Michel [0000-0001-7438-8990], Rutten, Bart P. F. [0000-0002-9834-6346], Kirkbride, James B. [0000-0003-3401-0824], O’Donovan, Michael C. [0000-0001-7073-2379], Vassos, Evangelos [0000-0001-6363-0438], Murray, Robin M. [0000-0003-0829-0519], Lewis, Cathryn M. [0000-0002-8249-8476], and Apollo - University of Cambridge Repository

Subjects
45, 692/699/476/1799, 692/53/2423, 45/43, article, 631/208/2489
Abstract

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.

Published
2021
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