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2. 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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4. Evidence, and replication thereof, that molecular-genetic and environmental risks for psychosis impact through an affective pathway

Author

Hersenen-Medisch 1, Brain, TN groep Adan, van Os, Jim, Pries, Lotta-Katrin, Ten Have, Margreet, de Graaf, Ron, van Dorsselaer, Saskia, Delespaul, Philippe, Bak, Maarten, Kenis, Gunter, Lin, Bochao D, Luykx, Jurjen J, Richards, Alexander L, Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M, Petrovic, Sanja Andric, Mirjanic, Tijana, Bernardo, Miguel, Mezquida, Gisela, Amoretti, Silvia, Bobes, Julio, Saiz, Pilar A, García-Portilla, María Paz, Sanjuan, Julio, Aguilar, Eduardo J, Santos, José Luis, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P, Atbaşoğlu, Cem, Ucok, Alp, Alptekin, Köksal, Saka, Meram Can, Arango, Celso, O'Donovan, Michael, Rutten, Bart P F, Guloksuz, Sinan, Hersenen-Medisch 1, Brain, TN groep Adan, van Os, Jim, Pries, Lotta-Katrin, Ten Have, Margreet, de Graaf, Ron, van Dorsselaer, Saskia, Delespaul, Philippe, Bak, Maarten, Kenis, Gunter, Lin, Bochao D, Luykx, Jurjen J, Richards, Alexander L, Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M, Petrovic, Sanja Andric, Mirjanic, Tijana, Bernardo, Miguel, Mezquida, Gisela, Amoretti, Silvia, Bobes, Julio, Saiz, Pilar A, García-Portilla, María Paz, Sanjuan, Julio, Aguilar, Eduardo J, Santos, José Luis, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P, Atbaşoğlu, Cem, Ucok, Alp, Alptekin, Köksal, Saka, Meram Can, Arango, Celso, O'Donovan, Michael, Rutten, Bart P F, and Guloksuz, Sinan

Published
2022

5. Examining the independent and joint effects of molecular genetic liability and environmental exposures in schizophrenia

Author

Guloksuz, Sinan, Pries, Lotta-Katrin, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J., Lin, Bochao D., Richards, Alexander L., Akdede, Berna, Binbay, Tolga, Altinyazar, Vesile, Yalinçetin, Berna, Gümüs-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulas, Halis, Cankurtaran, EylemSahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M., Petrovic, Sanja Andric, Mirjanic, Tijana, Bernardo, Miguel, Cabrera, Bibiana, Bobes, Julio, Saiz, Pilar A., García-Portilla, María Paz, Sanjuan, Julio, Aguilar, Eduardo J., Santos, José Luis, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P., Atbasoglu, Cem, Ucok, Alp, Alptekin, Köksal, Saka, Meram Can, Arango, Celso, O'Donovan, Michael, Rutten, Bart P.F., van Os, Jim, Alizadeh, Behrooz Z., van Amelsvoort, Therese, van Beveren, Nico J., Bruggeman, Richard, Cahn, Wiepke, de Haan, Lieuwe, Myin?Germeys, Inez, van Winkel, Ruud, APH - Mental Health, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Adult Psychiatry, Germeys, I, van Winkel, Ruud, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, Promovendi MHN, MUMC+: MA Niet Med Staf Psychiatrie (9), RS: MHeNs - R3 - Neuroscience, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), and MUMC+: MA Med Staf Spec Psychiatrie (9)

Subjects
cannabis, Psychosis, medicine.medical_specialty, polygenic risk, Season of birth, DISORDERS, VALIDATION, 03 medical and health sciences, 0302 clinical medicine, PSYCHOSIS, Journal Article, medicine, IMPUTATION, genetics, Gene–environment interaction, Psychological abuse, Psychiatry, Science & Technology, childhood trauma, INSTRUMENT, biology, business.industry, HERITABILITY, Research Reports, ASSOCIATION, medicine.disease, biology.organism_classification, 030227 psychiatry, gene-environment interaction, Psychiatry and Mental health, Physical abuse, Sexual abuse, bullying, RELIABILITY, Schizophrenia, Phychiatric Mental Health, Cannabis, Pshychiatric Mental Health, business, Life Sciences & Biomedicine, environment, 030217 neurology & neurosurgery, Diagnosis of schizophrenia
Abstract

Schizophrenia is a heritable complex phenotype associated with a background risk involving multiple common genetic variants of small effect and a multitude of environmental exposures. Early twin and family studies using proxy-genetic liability measures suggest gene-environment interaction in the etiology of schizophrenia spectrum disorders, but the molecular evidence is scarce. Here, by analyzing the main and joint associations of polygenic risk score for schizophrenia (PRS-SCZ) and environmental exposures in 1,699 patients with a diagnosis of schizophrenia spectrum disorders and 1,542 unrelated controls with no lifetime history of a diagnosis of those disorders, we provide further evidence for gene-environment interaction in schizophrenia. Evidence was found for additive interaction of molecular genetic risk state for schizophrenia (binary mode of PRS-SCZ above 75% of the control distribution) with the presence of lifetime regular cannabis use and exposure to early-life adversities (sexual abuse, emotional abuse, emotional neglect, and bullying), but not with the presence of hearing impairment, season of birth (winter birth), and exposure to physical abuse or physical neglect in childhood. The sensitivity analyses replacing the a priori PRS-SCZ at 75% with alternative cut-points (50% and 25%) confirmed the additive interaction. Our results suggest that the etiopathogenesis of schizophrenia involves genetic underpinnings that act by making individuals more sensitive to the effects of some environmental exposures. ispartof: WORLD PSYCHIATRY vol:18 issue:2 pages:173-182 ispartof: location:Italy status: published

Published
2019
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6. Replicated evidence that endophenotypic expression of schizophrenia polygenic risk is greater in healthy siblings of patients compared to controls, suggesting gene-environment interaction. The EUGEI study

Author

Brain, Hersenen-Medisch 1, Neurogenetica, TN groep Adan, van Os, Jim, Pries, Lotta-Katrin, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J, Lin, Bochao D, Richards, Alexander L, Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M, Petrovic, Sanja Andric, Mirjanic, Tijana, Bernardo, Miguel, Cabrera, Bibiana, Bobes, Julio, Saiz, Pilar A, García-Portilla, María Paz, Sanjuan, Julio, Aguilar, Eduardo J, Santos, José Luis, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P, Atbaşoğlu, Cem, Ucok, Alp, Alptekin, Köksal, Saka, Meram Can, Arango, Celso, O'Donovan, Michael, Rutten, Bart P F, Guloksuz, Sinan, Genetic Risk and Outcome Investigators (GROUP), Brain, Hersenen-Medisch 1, Neurogenetica, TN groep Adan, van Os, Jim, Pries, Lotta-Katrin, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J, Lin, Bochao D, Richards, Alexander L, Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M, Petrovic, Sanja Andric, Mirjanic, Tijana, Bernardo, Miguel, Cabrera, Bibiana, Bobes, Julio, Saiz, Pilar A, García-Portilla, María Paz, Sanjuan, Julio, Aguilar, Eduardo J, Santos, José Luis, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P, Atbaşoğlu, Cem, Ucok, Alp, Alptekin, Köksal, Saka, Meram Can, Arango, Celso, O'Donovan, Michael, Rutten, Bart P F, Guloksuz, Sinan, and Genetic Risk and Outcome Investigators (GROUP)

Published
2020

7. Evidence, and replication thereof, that molecular-genetic and environmental risks for psychosis impact through an affective pathway

Author

van Os, Jim, primary, Pries, Lotta-Katrin, additional, ten Have, Margreet, additional, de Graaf, Ron, additional, van Dorsselaer, Saskia, additional, Delespaul, Philippe, additional, Bak, Maarten, additional, Kenis, Gunter, additional, Lin, Bochao D., additional, Luykx, Jurjen J., additional, Richards, Alexander L., additional, Akdede, Berna, additional, Binbay, Tolga, additional, Altınyazar, Vesile, additional, Yalınçetin, Berna, additional, Gümüş-Akay, Güvem, additional, Cihan, Burçin, additional, Soygür, Haldun, additional, Ulaş, Halis, additional, Cankurtaran, Eylem Şahin, additional, Kaymak, Semra Ulusoy, additional, Mihaljevic, Marina M., additional, Petrovic, Sanja Andric, additional, Mirjanic, Tijana, additional, Bernardo, Miguel, additional, Mezquida, Gisela, additional, Amoretti, Silvia, additional, Bobes, Julio, additional, Saiz, Pilar A., additional, García-Portilla, María Paz, additional, Sanjuan, Julio, additional, Aguilar, Eduardo J., additional, Santos, José Luis, additional, Jiménez-López, Estela, additional, Arrojo, Manuel, additional, Carracedo, Angel, additional, López, Gonzalo, additional, González-Peñas, Javier, additional, Parellada, Mara, additional, Maric, Nadja P., additional, Atbaşoğlu, Cem, additional, Ucok, Alp, additional, Alptekin, Köksal, additional, Saka, Meram Can, additional, Arango, Celso, additional, O'Donovan, Michael, additional, Rutten, Bart P. F., additional, and Guloksuz, Sinan, additional

Published
2020
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8. Estimating Exposome Score for Schizophrenia Using Predictive Modeling Approach in Two Independent Samples: The Results From the EUGEI Study

Author

Pries, Lotta-Katrin, Lage-Castellanos, Agustin, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J, Lin, Bochao D, Richards, Alexander L, Akdede, Berna, Binbay, Tolga, Altinyazar, Vesile, Yalinçetin, Berna, Gümüs-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ula?, Halis, Cankurtaran, Eylem ?ahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M, Petrovic, Sanja Andric, Mirjanic, Tijana, Bernardo, Miguel, Cabrera, Bibiana, Bobes, Julio, Saiz, Pilar A, García-Portilla, María Paz, Sanjuan, Julio, Aguilar, Eduardo J, Santos, José Luis, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P, Atba?o?lu, Cem, Ucok, Alp, Alptekin, Köksal, Saka, Meram Can, Alizadeh, Behrooz Z, van Amelsvoort, Therese, Bruggeman, Richard, Cahn, Wiepke, de Haan, Lieuwe, van Winkel, Ruud, Rutten, Bart P F, van Os, Jim, Arango, Celso, O'Donovan, Michael, Guloksuz, Sinan, APH - Mental Health, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Adult Psychiatry, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Perceptual and Cognitive Neuroscience (PCN), Life Course Epidemiology (LCE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Promovendi MHN, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, Audition, RS: FPN CN 2, MUMC+: MA Niet Med Staf Psychiatrie (9), RS: MHeNs - R3 - Neuroscience, MUMC+: MA Psychiatrie (3), and RS: MHeNs School for Mental Health and Neuroscience

Subjects
Male, cannabis, Logistic regression, 0302 clinical medicine, Lasso (statistics), Adverse Childhood Experiences, Statistics, Odds Ratio, Child Abuse, POLYGENIC RISK, psychosis, Child, Psychiatry, SUMMER BIRTH, Framingham Risk Score, 3. Good health, Exposome, Psychiatry and Mental health, machine learning, Schizophrenia, Area Under Curve, Female, Marijuana Use, Seasons, Environment And Schizophrenia—Feature Editor: Jim van Os, Life Sciences & Biomedicine, environment, predictive modeling, Adult, DISORDERS, risk score, Young Adult, 03 medical and health sciences, PSYCHOSIS, medicine, Journal Article, Humans, Hearing Loss, METAANALYSIS, DEFICIT SCHIZOPHRENIA, ENVIRONMENT, Models, Statistical, Science & Technology, childhood trauma, Receiver operating characteristic, business.industry, Siblings, Bullying, Bayes Theorem, Child Abuse, Sexual, Odds ratio, hearing impairment, medicine.disease, 030227 psychiatry, schizophrenia, Logistic Models, ROC Curve, Sexual abuse, Case-Control Studies, business, CHILDHOOD ADVERSITIES, 030217 neurology & neurosurgery, winter birth
Abstract

The EUGEI project was supported by the grant agreement HEALTH-F2-2010-241909 from the European Community’s Seventh Framework Programme. The authors are grateful to the patients and their families for participating in the project. They also thank all research personnel involved in the GROUP project, in particular J. van Baaren, E. Veermans, G. Driessen, T. Driesen, E. van’t Hag and J. de Nijs. Bart PF Rutten was funded by a VIDI award number 91718336 from the Netherlands Scientific Organisation., Pries, L.-K., Lage-Castellanos, A., Delespaul, P., Kenis, G., Luykx, J.J., Lin, B.D., Richards, A.L., Akdede, B., Binbay, T., Altinyazar, V., Yalinçetin, B., Gümüş-Akay, G., Cihan, B., Soygür, H., Ulaş, H., Cankurtaran, E.Ş., Kaymak, S.U., Mihaljevic, M.M., Petrovic, S.A., Mirjanic, T., Bernardo, M., Cabrera, B., Bobes, J., Saiz, P.A., García-Portilla, M.P., Sanjuan, J., Aguilar, E.J., Santos, J.L., Jiménez-López, E., Arrojo, M., Carracedo, A., López, G., González-Peñas, J., Parellada, M., Maric, N.P., Atbaşoğlu, C., Ucok, A., Alptekin, K., Saka, M.C., Arango, C., O'Donovan, M., Rutten, B.P.F., van Os, J., Guloksuz, S.

Published
2019

9. White Noise Speech Illusions: A Trait-Dependent Risk Marker for Psychotic Disorder?

Author

Schepers, Elaine, Lousberg, Richel, Guloksuz, Sinan, Pries, Lotta-Katrin, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J., Lin, Bochao D., Richards, Alexander L., Akdede, Berna, Binbay, Tolga, Altinyazar, Vesile, Yalincetin, Berna, Gumus-Akay, Guvem, Cihan, Burcin, Soygur, Haldun, Ulas, Halis, Cankurtaran, Eylem Sahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M., Petrovic, Sanja Andric, Mirjanic, Tijana, Bernardo, Miguel, Cabrera, Bibiana, Bobes, Julio, Saiz, Pilar A., Paz Garcia-Portilla, Maria, Sanjuan, Julio, Aguilar, Eduardo J., Luis Santos, Jose, Jimenez-Lopez, Estela, Arrojo, Manuel, Carracedo, Angel, Lopez, Gonzalo, Gonzalez-Penas, Javier, Parellada, Mara, Maric, Nadja P., Atbasoglu, Cem, Ucok, Alp, Alptekin, Koksal, Saka, Meram Can, Arango, Celso, Rutten, Bart P. F., van Os, Jim, Schepers, Elaine, Lousberg, Richel, Guloksuz, Sinan, Pries, Lotta-Katrin, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J., Lin, Bochao D., Richards, Alexander L., Akdede, Berna, Binbay, Tolga, Altinyazar, Vesile, Yalincetin, Berna, Gumus-Akay, Guvem, Cihan, Burcin, Soygur, Haldun, Ulas, Halis, Cankurtaran, Eylem Sahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M., Petrovic, Sanja Andric, Mirjanic, Tijana, Bernardo, Miguel, Cabrera, Bibiana, Bobes, Julio, Saiz, Pilar A., Paz Garcia-Portilla, Maria, Sanjuan, Julio, Aguilar, Eduardo J., Luis Santos, Jose, Jimenez-Lopez, Estela, Arrojo, Manuel, Carracedo, Angel, Lopez, Gonzalo, Gonzalez-Penas, Javier, Parellada, Mara, Maric, Nadja P., Atbasoglu, Cem, Ucok, Alp, Alptekin, Koksal, Saka, Meram Can, Arango, Celso, Rutten, Bart P. F., and van Os, Jim

Published
2019

10. Survey of the European Psychiatric Association on the European status and perspectives in early detection and intervention in at-risk mental state and first-episode psychosis

Author

Maric, Nadja P., Petrovic, Sanja Andric, Raballo, Andrea, Rojnic-Kuzman, Martina, Klosterkoetter, Joachim, Riecher-Roessler, Anita, Maric, Nadja P., Petrovic, Sanja Andric, Raballo, Andrea, Rojnic-Kuzman, Martina, Klosterkoetter, Joachim, and Riecher-Roessler, Anita

Abstract

Aim Early detection/early intervention (ED/EI) programmes have been inconsistently implemented throughout Europe. We evaluated the ED/EI service distribution in European Psychiatric Association (EPA) member countries, considering indicators of socio-economic development, human and financial resources allocated in mental health (MH) as well as presence of a national branch of the Early Intervention in MH (IEPA). Contextually, we evaluated the duration of untreated psychosis (DUP) in relation to ED/EI service implementation. Methods EPA section Prevention of Mental Disorders conducted the cross-sectional survey administering the 16-item questionnaire to the representatives of its National Psychiatric Associations (NPAs). The survey addressed the Service status and profile, national guidelines, education and policy, DUP and IEPA national branch status. The data were analysed in relation to the indices of economic parameters and MH resources. Results Neither the national economic parameters, nor indices of MH financial resources were significantly associated with variables related to ED/EI implementation. However, more MH human resources per country were associated with shorter DUP. In comparison to countries without a national branch of IEPA, all of these with the branch had more MH human resources, ED/EI chapters in the national guidelines and services involving both adolescents and adults. Conclusions An unequal development of ED/EI services and related academic activities appears throughout Europe. The current results, besides providing a useful starting point to set the agenda for harmonizing ED/EI services, reveal that their implementation was more likely to be influenced by the IEPA membership status, rather than by country-specific financial and human resources allocated to MH.

Published
2019

11. White Noise Speech Illusions: A Trait-Dependent Risk Marker for Psychotic Disorder?

Author

Universidade de Santiago de Compostela. Departamento de Psiquiatría, Radioloxía, Saúde Pública, Enfermaría e Medicina, Schepers, Elaine, Lousberg, Richel, Guloksuz, Sinan, Pries, Lotta Katrin, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J., Lin, Bochao D., Richards, Alexander L., Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Semra, Ulusoy Kaymak, Mihaljevic, Marina M., Petrovic, Sanja Andric, Mirjanic, Tijana, Bernardo, Miguel, Cabrera, Bibiana, Bobes, Julio, Saiz, Pilar A., García Portilla, María Paz, Sanjuan, Julio, Aguilar, Eduardo J., Santos, José Luis, Jiménez López, Estela, Arrojo Romero, Manuel, Carracedo Álvarez, Ángel María, López, Gonzalo, González Peñas, Javier, Parellada, Mara, Maric, Nadja P., Atbaşoğlu, Cem, Ucok, Alp, Alptekin, Köksal, Saka, Meram Can, Arango, Celso, Rutten, Bart P.F., Os, Jim van, Universidade de Santiago de Compostela. Departamento de Psiquiatría, Radioloxía, Saúde Pública, Enfermaría e Medicina, Schepers, Elaine, Lousberg, Richel, Guloksuz, Sinan, Pries, Lotta Katrin, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J., Lin, Bochao D., Richards, Alexander L., Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Semra, Ulusoy Kaymak, Mihaljevic, Marina M., Petrovic, Sanja Andric, Mirjanic, Tijana, Bernardo, Miguel, Cabrera, Bibiana, Bobes, Julio, Saiz, Pilar A., García Portilla, María Paz, Sanjuan, Julio, Aguilar, Eduardo J., Santos, José Luis, Jiménez López, Estela, Arrojo Romero, Manuel, Carracedo Álvarez, Ángel María, López, Gonzalo, González Peñas, Javier, Parellada, Mara, Maric, Nadja P., Atbaşoğlu, Cem, Ucok, Alp, Alptekin, Köksal, Saka, Meram Can, Arango, Celso, Rutten, Bart P.F., and Os, Jim van

Abstract

Introduction: White noise speech illusions index liability for psychotic disorder in case–control comparisons. In the current study, we examined i) the rate of white noise speech illusions in siblings of patients with psychotic disorder and ii) to what degree this rate would be contingent on exposure to known environmental risk factors (childhood adversity and recent life events) and level of known endophenotypic dimensions of psychotic disorder [psychotic experiences assessed with the Community Assessment of Psychic Experiences (CAPE) scale and cognitive ability]. Methods: The white noise task was used as an experimental paradigm to elicit and measure speech illusions in 1,014 patients with psychotic disorders, 1,157 siblings, and 1,507 healthy participants. We examined associations between speech illusions and increasing familial risk (control -> sibling -> patient), modeled as both a linear and a categorical effect, and associations between speech illusions and level of childhood adversities and life events as well as with CAPE scores and cognitive ability scores. Results: While a positive association was found between white noise speech illusions across hypothesized increasing levels of familial risk (controls -> siblings -> patients) [odds ratio (OR) linear 1.11, 95% confidence interval (CI) 1.02–1.21, p = 0.019], there was no evidence for a categorical association with sibling status (OR 0.93, 95% CI 0.79–1.09, p = 0.360). The association between speech illusions and linear familial risk was greater if scores on the CAPE positive scale were higher (p interaction = 0.003; ORlow CAPE positive scale 0.96, 95% CI 0.85–1.07; ORhigh CAPE positive scale 1.26, 95% CI 1.09–1.46); cognitive ability was lower (p interaction < 0.001; ORhigh cognitive ability 0.94, 95% CI 0.84–1.05; ORlow cognitive ability 1.43, 95% CI 1.23–1.68); and exposure to childhood adversity was higher (p interaction < 0.001; ORlow adversity 0.92, 95% CI 0.82–1.04; ORhigh adversity 1.31, 95% CI 1.1

Published
2019

12. White noise speech illusions: A trait-dependent risk marker for psychotic disorder?

Author

Brain, Neurogenetica, TN groep Adan, Hersenen-Medisch 1, Schepers, Elaine, Lousberg, Richel, Guloksuz, Sinan, Pries, Lotta Katrin, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J., Lin, Bochao D., Richards, Alexander L., Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M., Petrovic, Sanja Andric, Mirjanic, Tijana, Bernardo, Miguel, Cabrera, Bibiana, Bobes, Julio, Saiz, Pilar A., García-Portilla, María Paz, Sanjuan, Julio, Aguilar, Eduardo J., Santos, José Luis, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P., Atbaşoğlu, Cem, Ucok, Alp, Alptekin, Köksal, Saka, Meram Can, Arango, Celso, Rutten, Bart P.F., van Os, Jim, Brain, Neurogenetica, TN groep Adan, Hersenen-Medisch 1, Schepers, Elaine, Lousberg, Richel, Guloksuz, Sinan, Pries, Lotta Katrin, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J., Lin, Bochao D., Richards, Alexander L., Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M., Petrovic, Sanja Andric, Mirjanic, Tijana, Bernardo, Miguel, Cabrera, Bibiana, Bobes, Julio, Saiz, Pilar A., García-Portilla, María Paz, Sanjuan, Julio, Aguilar, Eduardo J., Santos, José Luis, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P., Atbaşoğlu, Cem, Ucok, Alp, Alptekin, Köksal, Saka, Meram Can, Arango, Celso, Rutten, Bart P.F., and van Os, Jim

Published
2019

13. Replicated evidence that endophenotypic expression of schizophrenia polygenic risk is greater in healthy siblings of patients compared to controls, suggesting gene–environment interaction. The EUGEI study.

Author

van Os, Jim, Pries, Lotta-Katrin, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J., Lin, Bochao D., Richards, Alexander L., Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M., Petrovic, Sanja Andric, and Mirjanic, Tijana

Subjects
GENETICS of schizophrenia, SCHIZOPHRENIA risk factors, COGNITION, DISEASE susceptibility, ECOLOGY, GENETIC polymorphisms, GENETICS, PATHOLOGICAL psychology, PSYCHOSES, REPLICATION (Experimental design), PHENOTYPES
Abstract

Background: First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes. Methods: We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS. Results: In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group. Conclusions: The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder. [ABSTRACT FROM AUTHOR]

Published
2020
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15. Evidence, and replication thereof, that molecular-genetic and environmental risks for psychosis impact through an affective pathway.

Author

van Os J, Pries LK, Ten Have M, de Graaf R, van Dorsselaer S, Delespaul P, Bak M, Kenis G, Lin BD, Luykx JJ, Richards AL, Akdede B, Binbay T, Altınyazar V, Yalınçetin B, Gümüş-Akay G, Cihan B, Soygür H, Ulaş H, Cankurtaran EŞ, Kaymak SU, Mihaljevic MM, Petrovic SA, Mirjanic T, Bernardo M, Mezquida G, Amoretti S, Bobes J, Saiz PA, García-Portilla MP, Sanjuan J, Aguilar EJ, Santos JL, Jiménez-López E, Arrojo M, Carracedo A, López G, González-Peñas J, Parellada M, Maric NP, Atbaşoğlu C, Ucok A, Alptekin K, Saka MC, Arango C, O'Donovan M, Rutten BPF, and Guloksuz S

Subjects
Humans, Hallucinations etiology, Hallucinations genetics, Multifactorial Inheritance, Risk, Delusions diagnosis, Psychotic Disorders etiology, Psychotic Disorders genetics, Schizophrenia etiology, Schizophrenia genetics
Abstract

Background: There is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation., Methods: We analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 ( n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI ( n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls., Results: The impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: -0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465)., Conclusions: The results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.

Published
2022
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16. Estimating Exposome Score for Schizophrenia Using Predictive Modeling Approach in Two Independent Samples: The Results From the EUGEI Study.

Author

Pries LK, Lage-Castellanos A, Delespaul P, Kenis G, Luykx JJ, Lin BD, Richards AL, Akdede B, Binbay T, Altinyazar V, Yalinçetin B, Gümüş-Akay G, Cihan B, Soygür H, Ulaş H, Cankurtaran EŞ, Kaymak SU, Mihaljevic MM, Petrovic SA, Mirjanic T, Bernardo M, Cabrera B, Bobes J, Saiz PA, García-Portilla MP, Sanjuan J, Aguilar EJ, Santos JL, Jiménez-López E, Arrojo M, Carracedo A, López G, González-Peñas J, Parellada M, Maric NP, Atbaşoğlu C, Ucok A, Alptekin K, Saka MC, Arango C, O'Donovan M, Rutten BPF, van Os J, and Guloksuz S

Subjects
Adult, Adverse Childhood Experiences statistics & numerical data, Area Under Curve, Bayes Theorem, Case-Control Studies, Child, Child Abuse, Sexual statistics & numerical data, Female, Humans, Logistic Models, Machine Learning, Male, Models, Statistical, Odds Ratio, ROC Curve, Seasons, Young Adult, Bullying statistics & numerical data, Child Abuse statistics & numerical data, Exposome, Hearing Loss epidemiology, Marijuana Use epidemiology, Schizophrenia epidemiology, Siblings
Abstract

Exposures constitute a dense network of the environment: exposome. Here, we argue for embracing the exposome paradigm to investigate the sum of nongenetic "risk" and show how predictive modeling approaches can be used to construct an exposome score (ES; an aggregated score of exposures) for schizophrenia. The training dataset consisted of patients with schizophrenia and controls, whereas the independent validation dataset consisted of patients, their unaffected siblings, and controls. Binary exposures were cannabis use, hearing impairment, winter birth, bullying, and emotional, physical, and sexual abuse along with physical and emotional neglect. We applied logistic regression (LR), Gaussian Naive Bayes (GNB), the least absolute shrinkage and selection operator (LASSO), and Ridge penalized classification models to the training dataset. ESs, the sum of weighted exposures based on coefficients from each model, were calculated in the validation dataset. In addition, we estimated ES based on meta-analyses and a simple sum score of exposures. Accuracy, sensitivity, specificity, area under the receiver operating characteristic, and Nagelkerke's R2 were compared. The ESMeta-analyses performed the worst, whereas the sum score and the ESGNB were worse than the ESLR that performed similar to the ESLASSO and ESRIDGE. The ESLR distinguished patients from controls (odds ratio [OR] = 1.94, P < .001), patients from siblings (OR = 1.58, P < .001), and siblings from controls (OR = 1.21, P = .001). An increase in ESLR was associated with a gradient increase of schizophrenia risk. In reference to the remaining fractions, the ESLR at top 30%, 20%, and 10% of the control distribution yielded ORs of 3.72, 3.74, and 4.77, respectively. Our findings demonstrate that predictive modeling approaches can be harnessed to evaluate the exposome., (© The Author(s) 2019. 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
2019
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17. Survey of the European Psychiatric Association on the European status and perspectives in early detection and intervention in at-risk mental state and first-episode psychosis.

Author

Maric NP, Petrovic SA, Raballo A, Rojnic-Kuzman M, Klosterkötter J, and Riecher-Rössler A

Subjects
Cross-Sectional Studies, Early Medical Intervention, Europe, Health Resources economics, Health Resources statistics & numerical data, Humans, Mental Health Services economics, Mental Health Services statistics & numerical data, Societies, Medical, Surveys and Questionnaires, Time Factors, Time-to-Treatment statistics & numerical data, Early Diagnosis, Psychotic Disorders diagnosis, Psychotic Disorders therapy
Abstract

Aim: Early detection/early intervention (ED/EI) programmes have been inconsistently implemented throughout Europe. We evaluated the ED/EI service distribution in European Psychiatric Association (EPA) member countries, considering indicators of socio-economic development, human and financial resources allocated in mental health (MH) as well as presence of a national branch of the Early Intervention in MH (IEPA). Contextually, we evaluated the duration of untreated psychosis (DUP) in relation to ED/EI service implementation., Methods: EPA section "Prevention of Mental Disorders" conducted the cross-sectional survey administering the 16-item questionnaire to the representatives of its National Psychiatric Associations (NPAs). The survey addressed the Service status and profile, national guidelines, education and policy, DUP and IEPA national branch status. The data were analysed in relation to the indices of economic parameters and MH resources., Results: Neither the national economic parameters, nor indices of MH financial resources were significantly associated with variables related to ED/EI implementation. However, more MH human resources per country were associated with shorter DUP. In comparison to countries without a national branch of IEPA, all of these with the branch had more MH human resources, ED/EI chapters in the national guidelines and services involving both adolescents and adults., Conclusions: An unequal development of ED/EI services and related academic activities appears throughout Europe. The current results, besides providing a useful starting point to set the agenda for harmonizing ED/EI services, reveal that their implementation was more likely to be influenced by the IEPA membership status, rather than by country-specific financial and human resources allocated to MH., (© 2018 John Wiley & Sons Australia, Ltd.)

Published
2019
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