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1. Identifying gene-environment interactions in schizophrenia: Contemporary challenges for integrated, large-scale investigations

Author

Van Os, J. Rutten, B.P. Myin-Germeys, I. Delespaul, P. Viechtbauer, W. Van Zelst, C. Bruggeman, R. Reininghaus, U. Morgan, C. Murray, R.M. Di Forti, M. McGuire, P. Valmaggia, L.R. Kempton, M.J. Gayer-Anderson, C. Hubbard, K. Beards, S. Stilo, S.A. Onyejiaka, A. Bourque, F. Modinos, G. Tognin, S. Calem, M. O'Donovan, M.C. Owen, M.J. Holmans, P. Williams, N. Craddock, N. Richards, A. Humphreys, I. Meyer-Lindenberg, A. Leweke, F.M. Tost, H. Akdeniz, C. Rohleder, C. Bumb, J.M. Schwarz, E. Alptekin, K. Üçok, A. Saka, M.C. Atbagoǧlu, E.C. Gülöksüz, S. Gumus-Akay, G. Cihan, B. Karadaǧ, H. Soygür, H. Cankurtaran, E.S. Ulusoy, S. Akdede, B. Binbay, T. Ayer, A. Noyan, H. Karadayi, G. Akturan, E. Ulaş, H. Arango, C. Parellada, M. Bernardo, M. Sanjuán, J. Bobes, J. Arrojo, M. Santos, J.L. Cuadrado, P. Solano, J.J.R. Carracedo, A. Bernardo, E.G. Roldán, L. López, G. Cabrera, B. Cruz, S. Mesa, E.M.D. Pouso, M. Jiménez, E. Sánchez, T. Rapado, M. González, E. Martínez, C. Sánchez, E. Olmeda, M.S. De Haan, L. Velthorst, E. Van Der Gaag, M. Selten, J.-P. Van Dam, D. Van Der Ven, E. Van Der Meer, F. Messchaert, E. Kraan, T. Burger, N. Leboyer, M. Szoke, A. Schürhoff, F. Llorca, P.-M. Jamain, S. Tortelli, A. Frijda, F. Vilain, J. Galliot, A.-M. Baudin, G. Ferchiou, A. Richard, J.-R. Bulzacka, E. Charpeaud, T. Tronche, A.-M. De Hert, M. Van Winkel, R. Decoster, J. Derom, C. Thiery, E. Stefanis, N.C. Sachs, G. Aschauer, H. Lasser, I. Winklbaur, B. Schlögelhofer, M. Riecher-Rössler, A. Borgwardt, S. Walter, A. Harrisberger, F. Smieskova, R. Rapp, C. Ittig, S. Soguel-Dit-Piquard, F. Studerus, E. Klosterkötter, J. Ruhrmann, S. Paruch, J. Julkowski, D. Hilboll, D. Sham, P.C. Cherny, S.S. Chen, E.Y.H. Campbell, D.D. Li, M. Romeo-Casabona, C.M. Cirión, A.E. Mora, A.U. Jones, P. Kirkbride, J. Cannon, M. Rujescu, D. Tarricone, I. Berardi, D. Bonora, E. Seri, M. Marcacci, T. Chiri, L. Chierzi, F. Storbini, V. Braca, M. Minenna, M.G. Donegani, I. Fioritti, A. La Barbera, D. La Cascia, C.E. Mulè, A. Sideli, L. Sartorio, R. Ferraro, L. Tripoli, G. Seminerio, F. Marinaro, A.M. McGorry, P. Nelson, B. Amminger, G.P. Pantelis, C. Menezes, P.R. Del-Ben, C.M. Tenan, S.H.G. Shuhama, R. Ruggeri, M. Tosato, S. Lasalvia, A. Bonetto, C. Ira, E. Nordentoft, M. Krebs, M.-O. Barrantes-Vidal, N. Cristóbal, P. Kwapil, T.R. Brietzke, E. Bressan, R.A. Gadelha, A. Maric, N.P. Andric, S. Mihaljevic, M. Mirjanic, T.

Abstract

Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype. © 2014 The Author.

Published
2014

3. Identifying gene-environment interactions in schizophrenia: contemporary challenges for integrated, large-scale investigations

Author

Rosana Shuhama, Gonzalo López, Viviana Storbini, Tolga Binbay, Ma Soledad Olmeda, Maria Calem, Marina Mihaljevic, Christos Pantelis, Halis Ulaş, Eva Velthorst, Jeroen Decoster, J. Malte Bumb, Ruud van Winkel, E. Cem Atbasoglu, Wolfgang Viechtbauer, Mirella Ruggeri, Erich Studerus, Daniele La Barbera, Domenico Berardi, Anita Riecher-Rössler, Stefan Borgwardt, Elsje van der Ven, Charlotte Rapp, Desiree Hilboll, Mark van der Gaag, Chiara Bonetto, Marie-Odile Krebs, Silvia Tenan, Monika Schlögelhofer, Robin M. Murray, Caterina La Cascia, Philip McGuire, Simona A. Stilo, Desmond Campbell, Fabienne Harrisberger, Teresa Sánchez, Catherine Derom, Franck Schürhoff, Philippe Delespaul, Jose Luis Santos, Emilio Sánchez, Stephan Ruhrmann, Luigi Rocco Chiri, Sabrina Cruz, Handan Noyan, Dominika Julkowski, Celso Arango, Merete Nordentoft, Stacey S. Cherny, Anne-Marie Galliot, Daniella van Dam, María Pouso, Asier Urruela Mora, G. Paul Amminger, Enrique García Bernardo, Ahmet Ayer, Tijana Mirjanic, Andrei Szöke, Anna Walter, Antonio Lasalvia, Isla Humphreys, Flora Frijda, Lieuwe de Haan, Neus Barrantes-Vidal, Nigel Williams, Burçin Cihan, Matthew J. Kempton, Ceren Akdeniz, Tamar Kraan, Andrea Tortelli, Barnaby Nelson, Marta Di Forti, Angelo Fioritti, Pedro Cuadrado, Eylem Sahin Cankurtaran, Emanuel Schwarz, Andreas Meyer-Lindenberg, Ilaria Tarricone, Laura Ferraro, Dan Rujescu, Anne-Marie Tronche, Laura Roldan, Bibiana Cabrera, Alp Üçok, Craig Morgan, Julio Sanjuán, Mauro Braca, Julio Bobes, Eric Y.H. Chen, Michael Conlon O'Donovan, Peter Holmans, Harald N. Aschauer, Sarah Ittig, Covadonga Martínez, Iris Lasser, Emiliano González, Aitziber Emaldi Cirión, Rachele Sartorio, F. Seminerio, Rodrigo A. Bressan, Ulrich Reininghaus, Elisa Brietzke, François Bourque, G Tripoli, Inez Myin-Germeys, Aziz Ferchiou, Gemma Modinos, Grégoire Baudin, Fabienne Soguel-Dit-Piquard, Cristina Marta Del-Ben, Gabriele Sachs, Elçin Akturan, Manuel Arrojo, Thomas R. Kwapil, Alice Mulè, Eva Mª Díaz Mesa, Federico Chierzi, Köksal Alptekin, Floor J. van der Meer, Pak C. Sham, Jim van Os, Adanna Onyejiaka, Mara Parellada, Bart P. F. Rutten, Jeanne Vilain, Michael John Owen, Sarah Tosato, Haldan Soygür, A.M. Marinaro, Stefania Tognin, Evert Thiery, Cathrin Rohleder, Mary Cannon, Miaoxin Li, F. Markus Leweke, Marc De Hert, Marta Rapado, Maria Gabriella Minenna, Pierre-Michel Llorca, Alexander Richards, Stéphane Jamain, Elles Messchaert, Nadja P. Maric, Semra Ulusoy, Elisa Ira, Peter G. Jones, Paulo Rossi Menezes, Patrick D. McGorry, Bernadette Winklbaur, Stephanie Beards, Nadine Burger, Güvem Gümüş-Akay, Marion Leboyer, James B. Kirkbride, Sinan Guloksuz, Ary Gadelha, E. Bulzacka, Carlos M. Romeo-Casabona, Gülşah Karadayı, Jean-Paul Selten, José Juan Rodríguez Solano, Kathryn Hubbard, Estela Jiménez, Thomas Charpeaud, Nikos C. Stefanis, Lucia Sideli, Miguel Bernardo, Jean-Romain Richard, Ivonne Donegani, Marco Seri, Lucia Valmaggia, Julia Paruch, Catherine van Zelst, Meram Can Saka, Heike Tost, Renata Smieskova, Thomas Marcacci, Nicholas John Craddock, Berna Binnur Akdede, Joachim Klosterkötter, Richard Bruggeman, Charlotte Gayer-Anderson, Sanja Andric, Elena Bonora, Angel Carracedo, Hasan Karadağ, Paula Cristobal, ANS - Amsterdam Neuroscience, Adult Psychiatry, Graduate School, Perceptual and Cognitive Neuroscience (PCN), Maastricht Univ, Kings Coll London, Mondriaan Mental Hlth Trust, Univ Groningen, Cardiff Univ, Cent Inst Mental Hlth, Dokuz Eylul Univ, Istanbul Univ, Ankara Univ, Yale Univ, Middle E Tech Univ, Diskapi YB Res & Training Hosp, Turkish Federat Schizophrenia Assoc, Ataturk Training & Res Hosp, Manisa Mental Hlth Hosp, Univ Complutense, Univ Barcelona, Univ Valencia, Univ Oviedo, Univ Santiago de Compostela, Hosp Virgen de la Luz, Hosp Univ Infanta Leonor Hosp Virgen Torre, Hosp Clin Univ, Hosp Psiquiatr Conxo, Univ Amsterdam, Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, Parnassia Psychiat Inst, Rivierduinen Psychiat Inst, Grp Hosp Mondor, Hop Henri Mondor, Univ Paris Est, Fdn Fondamental, CMP B CHU, Univ Auvergne, EPS Maison Blanche, UPC KU Leuven, UPC, Katholieke Univ Leuven, Assoc Sci Res Multiple Births, Univ Ghent, Univ Athens, Med Univ Vienna, Psychiat Univ Clin Basel, Univ Cologne, Univ Hong Kong, Univ Basque Country, Univ Zaragoza, Univ Cambridge, UCL, Royal Coll Surgeons Ireland, Univ Munich, Univ Bologna, Local Hlth Trust, Univ Palermo, P Giaccone Gen Hosp, Univ Melbourne, Universidade de São Paulo (USP), Univ Verona, Copenhagen Univ Hosp, Univ Paris 05, Univ Autonoma Barcelona, St Pere Claver Fundacio Sanitaria, Univ N Carolina, CIBERSAM, Universidade Federal de São Paulo (UNIFESP), Univ Belgrade, van Os J, Rutten BP, Myin-Germeys I, Delespaul P, Viechtbauer W, van Zelst C, Bruggeman R, Reininghaus U, Morgan C, Murray RM, Di Forti M, McGuire P, Valmaggia LR, Kempton MJ, Gayer-Anderson C, Hubbard K, Beards S, Stilo SA, Onyejiaka A, Bourque F, Modinos G, Tognin S, Calem M, O'Donovan MC, Owen MJ, Holmans P, Williams N, Craddock N, Richards A, Humphreys I, Meyer-Lindenberg A, Leweke FM, Tost H, Akdeniz C, Rohleder C, Bumb JM, Schwarz E, Alptekin K, Üçok A, Saka MC, Atbaşoğlu EC, Gülöksüz S, Gumus-Akay G, Cihan B, Karadağ H, Soygür H, Cankurtaran EŞ, Ulusoy S, Akdede B, Binbay T, Ayer A, Noyan H, Karadayı G, Akturan E, Ulaş H, Arango C, Parellada M, Bernardo M, Sanjuán J, Bobes J, Arrojo M, Santos JL, Cuadrado P, Rodríguez Solano JJ, Carracedo A, García Bernardo E, Roldán L, López G, Cabrera B, Cruz S, Díaz Mesa EM, Pouso M, Jiménez E, Sánchez T, Rapado M, González E, Martínez C, Sánchez E, Olmeda MS, de Haan L, Velthorst E, van der Gaag M, Selten JP, van Dam D, van der Ven E, van der Meer F, Messchaert E, Kraan T, Burger N, Leboyer M, Szoke A, Schürhoff F, Llorca PM, Jamain S, Tortelli A, Frijda F, Vilain J, Galliot AM, Baudin G, Ferchiou A, Richard JR, Bulzacka E, Charpeaud T, Tronche AM, De Hert M, van Winkel R, Decoster J, Derom C, Thiery E, Stefanis NC, Sachs G, Aschauer H, Lasser I, Winklbaur B, Schlögelhofer M, Riecher-Rössler A, Borgwardt S, Walter A, Harrisberger F, Smieskova R, Rapp C, Ittig S, Soguel-dit-Piquard F, Studerus E, Klosterkötter J, Ruhrmann S, Paruch J, Julkowski D, Hilboll D, Sham PC, Cherny SS, Chen EY, Campbell DD, Li M, Romeo-Casabona CM, Emaldi Cirión A, Urruela Mora A, Jones P, Kirkbride J, Cannon M, Rujescu D, Tarricone I, Berardi D, Bonora E, Seri M, Marcacci T, Chiri L, Chierzi F, Storbini V, Braca M, Minenna MG, Donegani I, Fioritti A, La Barbera D, La Cascia CE, Mulè A, Sideli L, Sartorio R, Ferraro L, Tripoli G, Seminerio F, Marinaro AM, McGorry P, Nelson B, Amminger GP, Pantelis C, Menezes PR, Del-Ben CM, Gallo Tenan SH, Shuhama R, Ruggeri M, Tosato S, Lasalvia A, Bonetto C, Ira E, Nordentoft M, Krebs MO, Barrantes-Vidal N, Cristóbal P, Kwapil TR, Brietzke E, Bressan RA, Gadelha A, Maric NP, Andric S, Mihaljevic M, Mirjanic T, Clinical Psychology, EMGO+ - Mental Health, Van Os, J., Rutten, B., Myin Germeys, I., Delespaul, P., Viechtbauer, W., Van Zelst, C., Bruggeman, R., Reininghaus, U., Morgan, C., Murray, R., Di Forti, M., Mcguire, P., Valmaggia, L., Kempton, M., Gayer Anderson, C., Hubbard, K., Beards, S., Stilo, S., Onyejiaka, A., Bourque, F., Modinos, G., Tognin, S., Calem, M., O'Donovan, M., Owen, M., Holmans, P., Williams, N., Craddock, N., Richards, A., Humphreys, I., Meyer Lindenberg, A., Leweke, F., Tost, H., Akdeniz, C., Rohleder, C., Bumb, J., Schwarz, E., Alptekin, K., Üçok, A., Saka, M., Atbagoǧlu, E., Gülöksüz, S., Gumus Akay, G., Cihan, B., Karadaǧ, H., Soygür, H., Cankurtaran, E., Ulusoy, S., Akdede, B., Binbay, T., Ayer, A., Noyan, H., Karadayi, G., Akturan, E., Ulaş, H., Arango, C., Parellada, M., Bernardo, M., Sanjuán, J., Bobes, J., Arrojo, M., Santos, J., Cuadrado, P., Solano, J., Carracedo, A., Bernardo, E., Roldán, L., López, G., Cabrera, B., Cruz, S., Mesa, E., Pouso, M., Jiménez, E., Sánchez, T., Rapado, M., González, E., Martínez, C., Sánchez, E., Olmeda, M., De Haan, L., Velthorst, E., Van Der Gaag, M., Selten, J., Van Dam, D., Van Der Ven, E., Van Der Meer, F., Messchaert, E., Kraan, T., Burger, N., Leboyer, M., Szoke, A., Schürhoff, F., Llorca, P., Jamain, S., Tortelli, A., Frijda, F., Vilain, J., Galliot, A., Baudin, G., Ferchiou, A., Richard, J., Bulzacka, E., Charpeaud, T., Tronche, A., De Hert, M., Van Winkel, R., Decoster, J., Derom, C., Thiery, E., Stefanis, N., Sachs, G., Aschauer, H., Lasser, I., Winklbaur, B., Schlögelhofer, M., Riecher Rössler, A., Borgwardt, S., Walter, A., Harrisberger, F., Smieskova, R., Rapp, C., Ittig, S., Soguel Dit Piquard, F., Studerus, E., Klosterkötter, J., Ruhrmann, S., Paruch, J., Julkowski, D., Hilboll, D., Sham, P., Cherny, S., Chen, E., Campbell, D., Li, M., Romeo Casabona, C., Cirión, A., Mora, A., Jones, P., Kirkbride, J., Cannon, M., Rujescu, D., Tarricone, I., Berardi, D., Bonora, E., Seri, M., Marcacci, T., Chiri, L., Chierzi, F., Storbini, V., Braca, M., Minenna, M., Donegani, I., Fioritti, A., LA BARBERA, D., LA CASCIA, C., Mulè, A., Sideli, L., Sartorio, C., Ferraro, L., Tripoli, G., Seminerio, F., Marinaro, A., Mcgorry, P., Nelson, B., Amminger, G., Pantelis, C., Menezes, P., Del Ben, C., Tenan, S., Shuhama, R., Ruggeri, M., Tosato, S., Lasalvia, A., Bonetto, C., Ira, E., Nordentoft, M., Krebs, M., Barrantes Vidal, N., Cristóbal, P., Kwapil, T., Brietzke, E., Bressan, R., Gadelha, A., Maric, N., Andric, S., Mihaljevic, M., Mirjanic, T., Psychiatrie & Neuropsychologie, Promovendi MHN, and RS: MHeNs - R2 - Mental Health

Subjects
URBANICITY, Schizophrenia (object-oriented programming), CHILDHOOD, Genome-wide association study, VARIANTS, Social Environment, psychosi, 03 medical and health sciences, 0302 clinical medicine, PSYCHOSIS, epidemiology, gene-environment interaction, genetics, psychosis, schizophrenia, SDG 3 - Good Health and Well-being, RISK-FACTOR, Settore M-PSI/08 - Psicologia Clinica, Genetic variation, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Gene, Settore MED/25 - Psichiatria, METAANALYSIS, Scale (chemistry), Psychosis, Genetic variants, Environment and Schizophrenia Invited, CANNABIS USE, 3. Good health, 030227 psychiatry, Psychiatry and Mental health, Evolutionary biology, Identification (biology), Schizophrenic Psychology, Population Risk, genetic, Psychology, FOLLOW-UP, 030217 neurology & neurosurgery, FUTURE-DIRECTIONS, Clinical psychology
Abstract

European Community Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G x E), however, so far, thorough replication of findings is rare and G x E research still faces several conceptual and methodological challenges. in this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G x E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G x E in schizophrenia. While such investigations are now well underway, new challenges emerge for G x E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype. Maastricht Univ, Med Ctr, Dept Psychiat & Neuropsychol, Sch Mental Hlth & Neurosci,South Limburg Mental H, NL-6200 MD Maastricht, Netherlands Kings Coll London, Inst Psychiat, Dept Psychosis Studies, London WC2R 2LS, England Mondriaan Mental Hlth Trust, Maastricht, Heerlen, Netherlands Univ Groningen, Univ Med Ctr Groningen, Rob Giel Clin Res, Univ Ctr Psychiat, Groningen, Netherlands Kings Coll London, Inst Psychiat, Dept Hlth Serv & Populat Res, London WC2R 2LS, England Kings Coll London, Inst Psychiat, Dept Psychol, London WC2R 2LS, England Cardiff Univ, MRC, Ctr Neuropsychiat Genet, Cardiff CF10 3AX, S Glam, Wales Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, Mannheim, Germany Dokuz Eylul Univ, Sch Med, Dept Psychiat, Konak, Turkey Istanbul Univ, Istanbul Fac Med, Dept Psychiat, Psychot Disorders Res Unit, Istanbul, Turkey Ankara Univ, Sch Med, Dept Psychiat, Cebeci Hosp, TR-06100 Ankara, Turkey Ankara Univ, Brain Res Ctr, TR-06100 Ankara, Turkey Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA Middle E Tech Univ, Dept Psychol, TR-06531 Ankara, Turkey Diskapi YB Res & Training Hosp, Ankara, Turkey Turkish Federat Schizophrenia Assoc, Ankara, Turkey Ataturk Training & Res Hosp, Psychiat Clin, Ankara, Turkey Manisa Mental Hlth Hosp, Manisa, Turkey Istanbul Univ, Expt Med Res Inst, Dept Adv Neurol Sci, Istanbul Fac Med, Istanbul, Turkey Univ Complutense, IiSGM CIBERSAM, Dept Child & Adolescent Psychiat, Hosp Gen Univ Gregorio Maranon,Sch Med, E-28040 Madrid, Spain Univ Barcelona, Dept Psychiat, Hosp Clin, IDIBAPS,Ctr Invest Biomed Red Salud Mental CIBERS, Barcelona, Spain Univ Valencia, Sch Med, Dept Psychiat, Ctr Invest Biomed Red Salud Mental CIBERSAM, Valencia, Spain Univ Oviedo, Sch Med, Dept Med,Psychiat Area, Ctr Invest Biomed Red Salud Mental CIBERSAM, Oviedo, Spain Univ Santiago de Compostela, Dept Mental Hlth & Drug Addit Assistance, Hlth Serv Galicia,Psychiat Genet Grp IDIS, Hosp Clin,Ctr Invest Biomedica Red Salud Mental C, Santiago de Compostela 15706, Spain Hosp Virgen de la Luz, Serv Psiquiat, Dept Psychiat, Cuenca, Spain Hosp Univ Infanta Leonor Hosp Virgen Torre, Villa de Vallecas Mental Hlth Ctr, Villa de Vallecas Mental Hlth Dept, Madrid, Spain Hosp Univ Infanta Leonor Hosp Virgen Torre, Puente de Vallecas Mental Hlth Dept, Ctr Salud Mental Puente Vallecas, Madrid, Spain Hosp Clin Univ, Fdn Publ Galega Med Xenomica, Santiago de Compostela, Spain Univ Complutense, Sch Med, Hosp Gen Univ Gregorio Maranon, Dept Psychiat, E-28040 Madrid, Spain Hosp Psiquiatr Conxo, Santiago de Compostela, Spain Univ Amsterdam, Acad Med Ctr, Early Psychosis Sect, Dept Psychiat, NL-1105 AZ Amsterdam, Netherlands Vrije Univ Amsterdam, Dept Clin Psychol, Amsterdam, Netherlands EMGO Inst Hlth & Care Res, Amsterdam, Netherlands Parnassia Psychiat Inst, Dept Psychosis Res, the Hague, Netherlands Rivierduinen Psychiat Inst, Leiden, Netherlands Grp Hosp Mondor, AP HP, Creteil, France Hop Henri Mondor, INSERM, U955, Equipe 15, F-94010 Creteil, France Univ Paris Est, Fac Med, Creteil, France Fdn Fondamental, Creteil, France CMP B CHU, F-63003 Clermont Ferrand 1, France Univ Auvergne, EA 7280, Clermont Ferrand, France EPS Maison Blanche, Paris, France UPC KU Leuven, Dept Neurosci, UPC, Kortenberg, Belgium UPC, Dept Neurosci, Res Grp Psychiat, Leuven, Belgium Katholieke Univ Leuven, Univ Hosp Gasthuisberg, Dept Human Genet, Leuven, Belgium Assoc Sci Res Multiple Births, Ghent, Belgium Univ Ghent, Dept Neurol, Ghent Univ Hosp, B-9000 Ghent, Belgium Univ Athens, Sch Med, Eginit Hosp, Athens 11528, Greece Med Univ Vienna, Dept Psychiat & Psychotherapy, Vienna, Austria Psychiat Univ Clin Basel, Ctr Gender Res & Early Detect, Basel, Switzerland Psychiat Univ Clin Basel, Diagnost & Crisis Intervent Ctr, Basel, Switzerland Univ Cologne, Dept Psychiat & Psychotherapy, D-50931 Cologne, Germany Univ Hong Kong, Li Ka Shing Fac Med, Ctr Genom Sci, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China Univ Hong Kong, Li Ka Shing Fac Med, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China Univ Hong Kong, Queen Mary Hosp, Li Ka Shing Fac Med, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China Univ Hong Kong, Queen Mary Hosp, Li Ka Shing Fac Med, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China Univ Basque Country, Univ Deusto, Interuniv Chair Law & Human Genome Prov Govt Bisk, Bilbao, Bizkaia, Spain Univ Zaragoza, Zaragoza, Spain Univ Cambridge, Dept Psychiat, Cambridge, England UCL, Div Psychiat, London, England Royal Coll Surgeons Ireland, Beaumont Hosp, Educ & Res Ctr, Dept Psychiat, Dublin 9, Ireland Univ Munich, Dept Psychiat, Div Mol & Clin Neurobiol, Munich, Germany Univ Bologna, Alma Mater Studiorium, Psychiat Unit, Dept Med & Surg Sci, Bologna, Italy Univ Bologna, Alma Mater Studiorium, Genet Unit, Dept Med & Surg Sci, Bologna, Italy Local Hlth Trust, Dept Mental Hlth & Pathol Addict, Bologna, Italy Univ Palermo, Sect Psychiat, Dept Expt Biomed & Clin Neurosci, Palermo, Italy P Giaccone Gen Hosp, Unit Psychiat, Palermo, Italy Univ Melbourne, Ctr Youth Mental Hlth, Parkville, Vic 3052, Australia Univ Melbourne, Melbourne Neuropsychiat Ctr, Carlton, Vic, Australia Univ São Paulo, Fac Med, Dept Med Prevent, BR-01246903 São Paulo, Brazil Univ São Paulo, Nucleo Pesquina Saude Mental Populac, São Paulo, Brazil Univ São Paulo, Fac Med Ribeirao Preto, Dept Neurociencias & Ciencias Comportamento, BR-14049 Ribeirao Preto, Brazil Univ Verona, Sect Psychiat, Dept Publ Hlth & Community Med, I-37100 Verona, Italy Copenhagen Univ Hosp, Res Unit, Mental Hlth Ctr Copenhagen, Copenhagen, Denmark Univ Paris 05, Fac Med, Serv Hosp Univ, Hop St Anne, Paris, France Univ Autonoma Barcelona, Dept Psicol Clin & Salut, E-08193 Barcelona, Spain St Pere Claver Fundacio Sanitaria, Dept Salut Mental, Barcelona, Spain Univ N Carolina, Dept Psychol, Greensboro, NC 27412 USA CIBERSAM, Spanish Mental Hlth Res Network, Barcelona, Spain Universidade Federal de São Paulo, Dept Psychiat, PRISMA Early Intervent Program, São Paulo, Brazil Univ Belgrade, Sch Med, Beograd, Serbia Universidade Federal de São Paulo, Dept Psychiat, PRISMA Early Intervent Program, São Paulo, Brazil European Community: HEALTH-F2-2009-241909 Web of Science

Published
2014

4. Identifying gene-environment interactions in schizophrenia: contemporary challenges for integrated, large-scale investigations.

Author

van Os J, Rutten BP, Myin-Germeys I, Delespaul P, Viechtbauer W, van Zelst C, Bruggeman R, Reininghaus U, Morgan C, Murray RM, Di Forti M, McGuire P, Valmaggia LR, Kempton MJ, Gayer-Anderson C, Hubbard K, Beards S, Stilo SA, Onyejiaka A, Bourque F, Modinos G, Tognin S, Calem M, O'Donovan MC, Owen MJ, Holmans P, Williams N, Craddock N, Richards A, Humphreys I, Meyer-Lindenberg A, Leweke FM, Tost H, Akdeniz C, Rohleder C, Bumb JM, Schwarz E, Alptekin K, Üçok A, Saka MC, Atbaşoğlu EC, Gülöksüz S, Gumus-Akay G, Cihan B, Karadağ H, Soygür H, Cankurtaran EŞ, Ulusoy S, Akdede B, Binbay T, Ayer A, Noyan H, Karadayı G, Akturan E, Ulaş H, Arango C, Parellada M, Bernardo M, Sanjuán J, Bobes J, Arrojo M, Santos JL, Cuadrado P, Rodríguez Solano JJ, Carracedo A, García Bernardo E, Roldán L, López G, Cabrera B, Cruz S, Díaz Mesa EM, Pouso M, Jiménez E, Sánchez T, Rapado M, González E, Martínez C, Sánchez E, Olmeda MS, de Haan L, Velthorst E, van der Gaag M, Selten JP, van Dam D, van der Ven E, van der Meer F, Messchaert E, Kraan T, Burger N, Leboyer M, Szoke A, Schürhoff F, Llorca PM, Jamain S, Tortelli A, Frijda F, Vilain J, Galliot AM, Baudin G, Ferchiou A, Richard JR, Bulzacka E, Charpeaud T, Tronche AM, De Hert M, van Winkel R, Decoster J, Derom C, Thiery E, Stefanis NC, Sachs G, Aschauer H, Lasser I, Winklbaur B, Schlögelhofer M, Riecher-Rössler A, Borgwardt S, Walter A, Harrisberger F, Smieskova R, Rapp C, Ittig S, Soguel-dit-Piquard F, Studerus E, Klosterkötter J, Ruhrmann S, Paruch J, Julkowski D, Hilboll D, Sham PC, Cherny SS, Chen EY, Campbell DD, Li M, Romeo-Casabona CM, Emaldi Cirión A, Urruela Mora A, Jones P, Kirkbride J, Cannon M, Rujescu D, Tarricone I, Berardi D, Bonora E, Seri M, Marcacci T, Chiri L, Chierzi F, Storbini V, Braca M, Minenna MG, Donegani I, Fioritti A, La Barbera D, La Cascia CE, Mulè A, Sideli L, Sartorio R, Ferraro L, Tripoli G, Seminerio F, Marinaro AM, McGorry P, Nelson B, Amminger GP, Pantelis C, Menezes PR, Del-Ben CM, Gallo Tenan SH, Shuhama R, Ruggeri M, Tosato S, Lasalvia A, Bonetto C, Ira E, Nordentoft M, Krebs MO, Barrantes-Vidal N, Cristóbal P, Kwapil TR, Brietzke E, Bressan RA, Gadelha A, Maric NP, Andric S, Mihaljevic M, and Mirjanic T

Subjects
Genetic Predisposition to Disease, Humans, Schizophrenia epidemiology, Social Environment, Gene-Environment Interaction, Schizophrenia genetics, Schizophrenic Psychology
Abstract

Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype., (© The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2014
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5. Chances and risks of predicting psychosis.

Author

Ruhrmann S, Klosterkötter J, Bodatsch M, Nikolaides A, Julkowski D, Hilboll D, and Schultz-Lutter F

Subjects
Humans, Predictive Value of Tests, Psychotic Disorders prevention & control, Risk Factors, Psychotic Disorders diagnosis, Psychotic Disorders etiology
Abstract

Prevention is currently regarded a promising strategy for fighting the unfavorable consequences of psychosis. Yet, for the error probability inherent in any predictive approach, benefits and costs must be carefully weighed against each other. False attribution of risk may unnecessarily provoke stress and anxiety, and lead to unwarranted intervention exposure. However, clinical risk samples already exhibit psychopathological symptoms, cognitive and functional impairments, and help-seeking for mental problems. Thus, the risk of futile interventions is low as long as preventive measures also provide treatment for current complaints. Differentiation between still normal and clinically relevant mental states is another challenge as psychotic-like phenomena occur frequently in the general population, especially in younger adolescents. Reported prevalence rates vary with age, and if severe in terms of frequency and persistence, these phenomena considerably increase risk of psychosis in clinical as well as general population samples. Stigmatization is another concern, though insufficiently studied. Yet, at least more severe states of risk, which are accompanied by changes in thinking, feeling, and behavior, might lead to unfavorable, (self-) stigmatizing effects already by themselves, independent of any diagnostic "label," and to stress and confusion for the lack of understanding of what is going on. To further improve validity of risk criteria, advanced risk algorithms combining multi-step detection and risk stratification procedures should be developed. However, all prediction models possess a certain error probability. Thus, whether a risk model justifies preventive measures can only be decided by weighing the costs of unnecessary intervention and the benefits of avoiding a potentially devastating outcome.

Published
2012
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6. Pharmacological prevention and treatment in clinical at-risk states for psychosis.

Author

Ruhrmann S, Klosterkötter J, Bodatsch M, Bechdolf A, Schimmelmann BG, Nikolaides A, Hilboll D, and Schultze-Lutter F

Subjects
Humans, Psychotic Disorders psychology, Randomized Controlled Trials as Topic methods, Risk Factors, Treatment Outcome, Antidepressive Agents therapeutic use, Antipsychotic Agents therapeutic use, Fatty Acids, Omega-3 therapeutic use, Psychotic Disorders drug therapy, Psychotic Disorders prevention & control
Abstract

Over the last couple of decades, the treatment of psychoses has much advanced; yet, despite all progress, the individual and societal burden associated with psychosis and particularly schizophrenia has largely remained unchanged. Therefore, much hope is currently placed on indicated prevention as a mean to fight these burdens before they set in. Though the number of studies investigating pharmacological interventions is still limited, encouraging results have been reported from the pioneering trials, despite several methodological limitations. Furthermore, it has become clear that persons characterized by the at-risk criteria are already ill and do not only need preventive intervention, but also treatment. In consequence, outcome criteria have to be broadened to cover the current needs of the patients. As is indicated by a recent study successfully using Omega-3 fatty acids for both purposes, it may be promising to develop and investigate interventions especially for the at-risk state, independent of their effectiveness in manifest disease states. Treatment studies may become promoted by the proposed introduction of a new disorder category into DSM-V. Future prevention studies, however, need to solve the challenge of changing immediate transition rates, demanding for new risk enrichment strategies as a prerequisite for feasible trial designs.

Published
2012
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