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1. Examining the association between exposome score for schizophrenia and cognition in schizophrenia, siblings, and healthy controls: Results from the EUGEI study

Author

Fusar-Poli, Laura, Prachason, Thanavadee, Erzin, Gamze, Pries, Lotta-Katrin, Brondino, Natascia, Politi, Pierluigi, 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, Andric-Petrovic, Sanja, Mirjanic, Tijana, Bernardo, Miguel, Mezquida, Gisela, Amoretti, Silvia, Bobes, Julio, Saiz, Pilar A, García-Portilla, Maria Paz, Sanjuan, Julio, Escarti, Maria Jose, Santos, José Luis, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P, Atbaşoğlu, Cem, Üçok, Alp, Alptekin, Köksal, Saka, Meram Can, Arango, Celso, O'Donovan, Michael, van Os, Jim, Rutten, Bart PF, and Guloksuz, Sinan

Published
2023
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2. The association between cannabis use and facial emotion recognition in schizophrenia, siblings, and healthy controls: Results from the EUGEI study

Author

Fusar-Poli, Laura, Pries, Lotta-Katrin, van Os, Jim, Radhakrishnan, Rajiv, Pençe, Ayşegül Yay, Erzin, Gamze, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J, Lin, Bochao D, 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, Andric-Petrovic, Sanja, Mirjanic, Tijana, Bernardo, Miguel, Mezquida, Gisela, Amoretti, Silvia, Bobes, Julio, Saiz, Pilar A, García-Portilla, Maria 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, Üçok, Alp, Alptekin, Köksal, Saka, Meram Can, Aguglia, Eugenio, Arango, Celso, Rutten, Bart PF, and Guloksuz, Sinan

Published
2022
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3. Examining facial emotion recognition as an intermediate phenotype for psychosis: Findings from the EUGEI study

Author

Fusar-Poli, Laura, Pries, Lotta-Katrin, van Os, Jim, Erzin, Gamze, Delespaul, Philippe, Kenis, Gunter, Luykx, Juryen 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., Andric-Petrovic, Sanja, Mirjanic, Tijana, Bernardo, Miguel, Mezquida, Gisela, Amoretti, Silvia, Bobes, Julio, Saiz, Pilar A., García-Portilla, Maria 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, Üçok, Alp, Alptekin, Köksal, Saka, Meram Can, Aguglia, Eugenio, Arango, Celso, O'Donovan, Michael, Rutten, Bart P.F., and Guloksuz, Sinan

Published
2022
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4. 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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5. Examining the association between exposome score for schizophrenia and cognition in schizophrenia, siblings, and healthy controls: Results from the EUGEI study

Author

Bobes, Julio, Fusar-Poli, Laura, Prachason, Thanavadee, Erzin, Gamze, Pries, Lotta-Katrin, Brondino, Natascia, Politi, Pierluigi, 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, Andric-Petrovic, Sanja, Mirjanic, Tijana, Bernardo, Miguel, Mezquida, Gisela, Saka, Meram Can, Alptekin, Köksal, Üçok, Alp, Atbaşoğlu, Cem, Maric, Nadja P, Parellada, Mara, González-Peñas, Javier, López, Gonzalo, Carracedo, Angel, Arrojo, Manuel, Jiménez-López, Estela, Santos, José Luis, Escarti, Maria Jose, Sanjuan, Julio, García-Portilla, Maria Paz, Saiz, Pilar A, Amoretti, Silvia, Guloksuz, Sinan, Rutten, Bart PF, van Os, Jim, O'Donovan, Michael, and Arango, Celso

Subjects
Psychiatry and Mental health, Biological Psychiatry
Abstract

Background: People with schizophrenia spectrum disorders (SSD) frequently present cognitive impairments. Here, we investigated whether the exposome score for schizophrenia (ES-SCZ) - a cumulative environmental exposure score - was associated with impairments of neurocognition, social cognition, and perception in patients with SSD, their unaffected siblings, and healthy controls. Methods: This cross-sectional sample consisted of 1200 patients, 1371 siblings, and 1564 healthy controls. Neurocognition, social cognition, and perception were assesed using a short version of the Wechsler Adult Intelligence Scale–Third Edition (WAIS-III), the Degraded Facial Affect Recognition Task (DFAR), and the Benton Facial Recognition Test (BFR), respectively. Regression models were used to analyze the association between ES-SCZ and cognitive domains in each group. Results: There were no statistically significant associations between ES-SCZ and cognitive domains in SSD. ES-SCZ was negatively associated with T-score of cognition in siblings (B=-0.40, 95% CI -0.76 to -0.03) and healthy controls (B=-0.63, 95% CI -1.06 to -0.21). Additionally, ES-SCZ was positively associated with DFAR-total in siblings (B=0.83, 95% CI 0.26 to 1.40). Sensitivity analyses excluding cannabis use history from ES-SCZ largely confirmed the main findings. Conclusions: Longitudinal cohorts may elucidate how environmental exposures influence the onset and course of cognitive impairments in trans-syndromic psychosis spectrum.

Published
2023

6. 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

7. A replication study of JTC bias, genetic liability for psychosis and delusional ideation

Author

Hersenen-Medisch 1, Brain, TN groep Adan, Laboranten CT Radiologie, Henquet, Cécile, van Os, Jim, Pries, Lotta K, Rauschenberg, Christian, 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 S, Kaymak, Semra U, Mihaljevic, Marina M, Petrovic, Sanja S, Mirjanic, Tijana, Bernardo, Miguel, Mezquida, Gisela, Amoretti, Silvia, Bobes, Julio, Saiz, Pilar A, García-Portilla, Maria P, Sanjuan, Julio, Aguilar, Eduardo J, Santos, Jose L, 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 C, Arango, Celso, O'Donovan, Michael, Rutten, Bart P F, Gülöksüz, Sinan, Hersenen-Medisch 1, Brain, TN groep Adan, Laboranten CT Radiologie, Henquet, Cécile, van Os, Jim, Pries, Lotta K, Rauschenberg, Christian, 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 S, Kaymak, Semra U, Mihaljevic, Marina M, Petrovic, Sanja S, Mirjanic, Tijana, Bernardo, Miguel, Mezquida, Gisela, Amoretti, Silvia, Bobes, Julio, Saiz, Pilar A, García-Portilla, Maria P, Sanjuan, Julio, Aguilar, Eduardo J, Santos, Jose L, 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 C, Arango, Celso, O'Donovan, Michael, Rutten, Bart P F, and Gülöksüz, Sinan

Published
2022

8. 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

9. A replication study of JTC bias, genetic liability for psychosis and delusional ideation.

Author

Henquet, Cécile, van Os, Jim, Pries, Lotta K., Rauschenberg, Christian, 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 S., Kaymak, Semra U., and Mihaljevic, Marina M.

Subjects
RELATIVE medical risk, HALLUCINATIONS, DELUSIONS, GENETICS, CONFIDENCE intervals, PSYCHOSES, SCHIZOPHRENIA, TASK performance, COGNITION, PATIENTS' attitudes, DESCRIPTIVE statistics, PSYCHOSOCIAL factors
Abstract

Background: This study attempted to replicate whether a bias in probabilistic reasoning, or 'jumping to conclusions'(JTC) bias is associated with being a sibling of a patient with schizophrenia spectrum disorder; and if so, whether this association is contingent on subthreshold delusional ideation. Methods: Data were derived from the EUGEI project, a 25-centre, 15-country effort to study psychosis spectrum disorder. The current analyses included 1261 patients with schizophrenia spectrum disorder, 1282 siblings of patients and 1525 healthy comparison subjects, recruited in Spain (five centres), Turkey (three centres) and Serbia (one centre). The beads task was used to assess JTC bias. Lifetime experience of delusional ideation and hallucinatory experiences was assessed using the Community Assessment of Psychic Experiences. General cognitive abilities were taken into account in the analyses. Results: JTC bias was positively associated not only with patient status but also with sibling status [adjusted relative risk (aRR) ratio : 4.23 CI 95% 3.46–5.17 for siblings and aRR: 5.07 CI 95% 4.13–6.23 for patients]. The association between JTC bias and sibling status was stronger in those with higher levels of delusional ideation (aRR interaction in siblings: 3.77 CI 95% 1.67–8.51, and in patients: 2.15 CI 95% 0.94–4.92). The association between JTC bias and sibling status was not stronger in those with higher levels of hallucinatory experiences. Conclusions: These findings replicate earlier findings that JTC bias is associated with familial liability for psychosis and that this is contingent on the degree of delusional ideation but not hallucinations. [ABSTRACT FROM AUTHOR]

Published
2022
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10. 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

11. 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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12. A replication study of JTC bias, genetic liability for psychosis and delusional ideation

Author

Henquet, Cécile, primary, van Os, Jim, additional, Pries, Lotta K., additional, Rauschenberg, Christian, additional, Delespaul, Philippe, additional, Kenis, Gunter, additional, Luykx, Jurjen J., additional, Lin, Bochao D., 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 S., additional, Kaymak, Semra U., additional, Mihaljevic, Marina M., additional, Petrovic, Sanja S., additional, Mirjanic, Tijana, additional, Bernardo, Miguel, additional, Mezquida, Gisela, additional, Amoretti, Silvia, additional, Bobes, Julio, additional, Saiz, Pilar A., additional, García-Portilla, Maria P., additional, Sanjuan, Julio, additional, Aguilar, Eduardo J., additional, Santos, Jose L., 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 C., additional, Arango, Celso, additional, O'Donovan, Michael, additional, Rutten, Bart P.F., additional, and Gülöksüz, Sinan, additional

Published
2020
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13. 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

14. 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

15. 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

16. 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

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

Author

Schepers, Elaine, primary, Lousberg, Richel, additional, Guloksuz, Sinan, additional, Pries, Lotta-Katrin, additional, Delespaul, Philippe, additional, Kenis, Gunter, additional, Luykx, Jurjen J., additional, Lin, Bochao D., 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, Şahin Cankurtaran, Eylem, additional, Ulusoy Kaymak, Semra, additional, Mihaljevic, Marina M., additional, Andric Petrovic, Sanja, additional, Mirjanic, Tijana, additional, Bernardo, Miguel, additional, Cabrera, Bibiana, additional, Bobes, Julio, additional, Saiz, Pilar A., additional, García-Portilla, María Paz, additional, Sanjuan, Julio, additional, Aguilar, Eduardo J., additional, Luis Santos, José, 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, Can Saka, Meram, additional, Arango, Celso, additional, Rutten, Bart P.F., additional, and van Os, Jim, additional

Published
2019
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18. 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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19. 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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20. Examining the association between exposome score for schizophrenia and functioning in schizophrenia, siblings, and healthy controls: Results from the EUGEI study.

Author

Erzin G, Pries LK, van Os J, Fusar-Poli L, Delespaul P, Kenis G, Luykx JJ, Lin BD, 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, Andric-Petrovic S, 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 MC, Rutten BPF, and Guloksuz S

Subjects
Cross-Sectional Studies, Humans, Siblings, Exposome, Psychotic Disorders, Schizophrenia genetics
Abstract

Background: A cumulative environmental exposure score for schizophrenia (exposome score for schizophrenia [ES-SCZ]) may provide potential utility for risk stratification and outcome prediction. Here, we investigated whether ES-SCZ was associated with functioning in patients with schizophrenia spectrum disorder, unaffected siblings, and healthy controls., Methods: This cross-sectional sample consisted of 1,261 patients, 1,282 unaffected siblings, and 1,525 healthy controls. The Global Assessment of Functioning (GAF) scale was used to assess functioning. ES-SCZ was calculated based on our previously validated method. The association between ES-SCZ and the GAF dimensions (symptom and disability) was analyzed by applying regression models in each group (patients, siblings, and controls). Additional models included polygenic risk score for schizophrenia (PRS-SCZ) as a covariate., Results: ES-SCZ was associated with the GAF dimensions in patients (symptom: B = -1.53, p-value = 0.001; disability: B = -1.44, p-value = 0.001), siblings (symptom: B = -3.07, p-value < 0.001; disability: B = -2.52, p-value < 0.001), and healthy controls (symptom: B = -1.50, p-value < 0.001; disability: B = -1.31, p-value < 0.001). The results remained the same after adjusting for PRS-SCZ. The degree of associations of ES-SCZ with both symptom and disability dimensions were higher in unaffected siblings than in patients and controls. By analyzing an independent dataset (the Genetic Risk and Outcome of Psychosis study), we replicated the results observed in the patient group., Conclusions: Our findings suggest that ES-SCZ shows promise for enhancing risk prediction and stratification in research practice. From a clinical perspective, ES-SCZ may aid in efforts of clinical characterization, operationalizing transdiagnostic clinical staging models, and personalizing clinical management.

Published
2021
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21. 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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