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1. Premorbid Adjustment and IQ in Patients With First-Episode Psychosis: A Multisite Case-Control Study of Their Relationship With Cannabis Use

Author

Ferraro, Laura, La Cascia Caterina, Quattrone, Diego, Sideli, Lucia, Matranga, Domenica, Capuccio, Veronica, Tripoli, Giada, Gayer-Anderson, Charlotte, Morgan, Craig, Sami Musa, B., Sham, Pak, de Haan Lieuwe, Velthorst, Eva, Jongsma Hannah, E., Kirkbride James, B, Rutten Bart, P. F., Richards Alexander, L, Roldan, Laura, Arango, Celso, Bernardo, Miquel, Bobes, Julio, Sanjuan, Julio, Santos Jose Luis, Arrojo, Manuel, Tarricone, Ilaria, Tortelli, Andrea, Szöke, Andrei, Del-Ben Cristina Marta, Selten, Jean-Paul, Lynskey, Michael, Jones Peter, B., Van Os Jim, La Barbera Daniele, Eu-Gei WP2 Group (Amoretti, S., Baudin, G., Beards, S., Berardi, D., Bonetto, C., Cabrera, B., Carracedo, A., Charpeaud, T., Costas, J., Cristofalo, D., Cuadrado, P., Ferchiou, A., Franke, N., Frijda, F., García Bernardo, E., Garcia-Portilla, P., González Peñas, J., González, E., Hubbard, K., Jamain, S., Jiménez-López, E., Lasalvia, A., Leboyer, M., López Montoya, G., Lorente-Rovira, E., Díaz-Caneja, C. M., Marcelino Loureiro, C., Marrazzo, G., Martínez, C., Matteis, M., Messchaart, E., Moltó, M. D., Moreno, C., Juan, N., Olmeda, M. S., Parellada, M., Pignon, B., Rapado, M., Richard, J. -R., Rodríguez Solano, J. J., Rossi Menezes, P., Ruggeri, M., Sáiz, P. A., Sánchez-Gutierrez, T., Sánchez, E., Sartorio, C., Schürhoff, F., Seminerio, F., Shuhama, R., Stilo, S. A., Termorshuizen, F., Tosato, S., Tronche, A. -M., Van Dam, D., Van Der Ven, E. )., Murray Robin, M., Di Forti Marta, Ferraro, Laura, La Cascia, Caterina, Quattrone, Diego, Sideli, Lucia, Matranga, Domenica, Capuccio, Veronica, Tripoli, Giada, Gayer-Anderson, Charlotte, Morgan, Craig, Sami, Musa B, Sham, Pak, de Haan, Lieuwe, Velthorst, Eva, Jongsma, Hannah E, Kirkbride, James B, Rutten, Bart P F, Richards, Alexander L, Roldan, Laura, Arango, Celso, Bernardo, Miquel, Bobes, Julio, Sanjuan, Julio, Santos, Jose Lui, Arrojo, Manuel, Tarricone, Ilaria, Tortelli, Andrea, Szöke, Andrei, Del-Ben, Cristina Marta, Selten, Jean-Paul, Lynskey, Michael, Jones, Peter B, Van Os, Jim, La Barbera, Daniele, Murray, Robin M, Di Forti, Marta, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Adult Psychiatry, APH - Mental Health, MUMC+: MA Psychiatrie (3), Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience, and RS: MHeNs - R2 - Mental Health

Subjects
Male, cognition, Intelligence, Comorbidity, SUBSTANCE USE DISORDERS, 0302 clinical medicine, Settore MED/48 -Scienze Infermierist. e Tecn. Neuro-Psichiatriche e Riabilitat, Medicine, PREDICTORS, RISK, education, education.field_of_study, biology, Cognition, Middle Aged, Psychosocial Functioning, sociability, Psychiatry and Mental health, Schizophrenia, Female, Marijuana Use, Social Adjustment, MENTAL-HEALTH, Adult, medicine.medical_specialty, Psychosis, Adolescent, Population, 1ST EPISODE, DRUG-USE, preillness, Settore MED/01 - Statistica Medica, Young Adult, 03 medical and health sciences, AGE, Settore M-PSI/08 - Psicologia Clinica, Humans, Cognitive skill, Psychiatry, Settore MED/25 - Psichiatria, business.industry, Case-control study, preillne, biology.organism_classification, medicine.disease, EDUCAÇÃO, 030227 psychiatry, schizophrenia, Psychotic Disorders, Case-Control Studies, ONSET, Cannabis, NEUROCOGNITION, business, marijuana, Neurocognitive, 030217 neurology & neurosurgery, Regular Articles
Abstract

Psychotic patients with a lifetime history of cannabis use generally show better cognitive functioning than other psychotic patients. Some authors suggest that cannabis-using patients may have been less cognitively impaired and less socially withdrawn in their premorbid life. Using a dataset comprising 948 patients with first-episode psychosis (FEP) and 1313 population controls across 6 countries, we examined the extent to which IQ and both early academic (Academic Factor [AF]) and social adjustment (Social Factor [SF]) are related to the lifetime frequency of cannabis use in both patients and controls. We expected a higher IQ and a better premorbid social adjustment in psychotic patients who had ever used cannabis compared to patients without any history of use. We did not expect such differences in controls. In both patients and controls, IQ was 3 points higher among occasional-users than in never-users (mean difference [Mdiff] = 2.9, 95% CI = [1.2, 4.7]). Both cases and control daily-users had lower AF compared to occasional (Mdiff = −0.3, 95% CI = [−0.5; −0.2]) and never-users (Mdiff = −0.4, 95% CI = [−0.6; −0.2]). Finally, patient occasional (Mdiff = 0.3, 95% CI = [0.1; 0.5]) and daily-users (Mdiff = 0.4, 95% CI = [0.2; 0.6]) had better SF than their never-using counterparts. This difference was not present in controls (Fgroup*frequency(2, 2205) = 4.995, P = .007). Our findings suggest that the better premorbid social functioning of FEP with a history of cannabis use may have contributed to their likelihood to begin using cannabis, exposing them to its reported risk-increasing effects for Psychotic Disorders.

Published
2019
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2. 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
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3. Psychotic Experiences Are Associated With Paternal Age But Not With Delayed Fatherhood in a Large, Multinational, Community Sample

Author

Schürhoff, Franck, Pignon, Baptiste, Lajnef, Mohamed, Denis, Romain, Rutten, Bart, Morgan, Craig, Murray, Robin M, Leboyer, Marion, van Os, Jim, Szöke, Andrei, EU-GEI WP2 Group Author, Ruggeri, Mirella, Tosato, Sarah, Pignon, Baptiste, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Pôle de Psychiatrie [Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital H. Mondor - A. Chenevier, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Fondation FondaMental [Créteil], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], King‘s College London, Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, MUMC+: MA Psychiatrie (3), Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience, RS: MHeNs - R2 - Mental Health, and MUMC+: Hersen en Zenuw Centrum (3)

Subjects
Psychosis, medicine.medical_specialty, SYMPTOMS, paternal age, Schizotypy, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Population, schizotypy, 03 medical and health sciences, 0302 clinical medicine, SCHIZOTYPAL DIMENSIONS, SCHIZOPHRENIA, ADOLESCENTS, Epidemiology, risk factors, Medicine, media_common.cataloged_instance, psychotic experiences, European union, education, METAANALYSIS, media_common, Subclinical infection, GENERAL-POPULATION, education.field_of_study, business.industry, Confounding, medicine.disease, PARENTAL AGE, CAPE, 030227 psychiatry, MODEL, Psychiatry and Mental health, CONTINUUM, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Schizophrenia, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, RISK-FACTORS, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, epidemiology, business, 030217 neurology & neurosurgery, Regular Articles, Demography
Abstract

Advanced paternal age has been consistently associated with an increased risk of schizophrenia. It is less known if such an association also exists with subclinical/attenuated forms of psychosis. Additionally, it has been suggested that it is not paternal age per se, but rather delayed fatherhood, as a marker of a genetic liability of psychosis, that is the cause of the association. The aim of the current study was to examine whether paternal age and/or delayed fatherhood (paternity age) predict self-reported positive, negative, and/or depressive dimensions of psychosis in a large sample from the general population. The sample (N = 1465) was composed of control subjects from the 6 countries participating in the European Union Gene-Environment Interaction study. The CAPE, a self-report questionnaire, was used to measure dimensions of subclinical psychosis. Paternal age at the time of respondents’ birth and age of paternity were assessed by self-report. We assessed the influence of the variables of interest (paternal age or paternity age) on CAPE scores after adjusting for potential confounders (age, gender, and ethnicity). Paternal age was positively associated with the positive dimension of the CAPE. By contrast, paternity age was not associated with any of the psychosis dimensions assessed by the CAPE. Thus, our results do not support the idea that delayed fatherhood explains the association between age of paternity and psychosis risk. Furthermore, our results provide arguments for the hypothesis of an etiologic continuum of psychosis.

Published
2020
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4. The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study

Author

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

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

Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03–0.33) and positive (B = 0.19; 95%CI 0.03–0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and the general and affective dimensions in FEP. Daily and current cannabis use were associated with the positive dimensions in FEP (B = 0.31; 95%CI 0.11–0.52) and in controls (B = 0.26; 95%CI 0.06–0.46), over and above SZ-PRS. We provide evidence that genetic liability to schizophrenia and cannabis use map onto transdiagnostic symptom dimensions, supporting the validity and utility of the dimensional representation of psychosis. In our sample, genetic liability to schizophrenia correlated with more severe psychosis presentation, and cannabis use conferred risk to positive symptomatology beyond the genetic risk. Our findings support the hypothesis that psychotic experiences in the general population have similar genetic substrates as clinical disorders.

Published
2021
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5. 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 PF, 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 JP, Kahn, Rene S, Schirmbeck, Frederike, Van Winkel, Ruud, EU-GEI High Risk Study, Reichenberg, Abraham, Velthorst, Eva [0000-0002-9240-2909], Mollon, Josephine [0000-0003-4557-1838], Murray, Robin M [0000-0003-0829-0519], Amoretti, Silvia [0000-0001-6017-2734], Bobes, Julio [0000-0003-2187-4033], Atbaşoğlu, Cem [0000-0002-8211-6095], Del-Ben, Cristina Marta [0000-0003-0145-9975], Jones, Peter B [0000-0002-0387-880X], Kirkbride, James B [0000-0003-3401-0824], Tosato, Sarah [0000-0002-9665-7538], Llorca, Pierre-Michel [0000-0001-7438-8990], Menezes, Paulo Rossi [0000-0001-6330-3314], Bressan, Rodrigo A [0000-0002-0868-4449], Pantelis, Chris [0000-0002-9565-0238], Rutten, Bart PF [0000-0002-9834-6346], Alizadeh, Behrooz Z [0000-0002-1415-8007], Simons, Claudia JP [0000-0002-7637-3589], Kahn, Rene S [0000-0001-5909-8004], and Apollo - University of Cambridge Repository

Subjects
Adult, Cognition, Cross-Sectional Studies, Psychotic Disorders, Siblings, Humans, Neuropsychological Tests, Aged
Abstract

Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = -0.45 to -0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = -0.14 to -0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = -0.88 to -0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = -0.13 to -0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = -0.21 to -0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders.

Published
2021

6. The EUropean Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI): Incidence and First-Episode Case-Control Programme

Author

Gayer-Anderson, Charlotte, Jongsma, Hannah E, Di Forti, Marta, Quattrone, Diego, Velthorst, Eva, De Haan, Lieuwe, Selten, Jean-Paul, Szöke, Andrei, Llorca, Pierre-Michel, Tortelli, Andrea, Arango, Celso, Bobes, Julio, Bernardo, Miguel, Sanjuán, Julio, Santos, José Luis, Arrojo, Manuel, Parellada, Mara, Tarricone, Ilaria, Berardi, Domenico, Ruggeri, Mirella, Lasalvia, Antonio, Ferraro, Laura, La Cascia, Caterina, La Barbera, Daniele, Menezes, Paulo Rossi, Del-Ben, Cristina Marta, EU-GEI WP2 Group, Rutten, Bart P, Van Os, Jim, Jones, Peter B, Murray, Robin M, Kirkbride, James B, Morgan, Craig, Gayer-Anderson, Charlotte [0000-0003-1636-889X], and Apollo - University of Cambridge Repository

Subjects
Adult, Male, Adolescent, Incidence, Middle Aged, First-episode psychosis, Environment–environment interactions, EU-GEI, Gene–environment interactions, Europe, Young Adult, Case-Control Studies, Ethnicity, Schizophrenia, Humans, Female, Gene-Environment Interaction, Case–control, Brazil
Abstract

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

Published
2020

7. Long-term cognitive trajectories and heterogeneity in patients with schizophrenia and their unaffected siblings

Author

Islam, Md. A., Habtewold, T. D., van Es, F. D., Quee, P. J., van den Heuvel, E. R., Alizadeh, B. Z., Bruggeman, R., Bartels-Velthuis, Agna A., van Beveren, Nico J., Cahn, Wiepke, de Haan, Lieuwe, Delespaul, Philippe, Meijer, Carin J., Myin-Germeys, Inez, Kahn, Rene S., Schirmbeck, Frederike, Simons, Claudia J. P., van Amelsvoort, Therese, van Haren, Neeltje E., van Os, Jim, van Winkel, Ruud, PharmacoTherapy, -Epidemiology and -Economics, Life Course Epidemiology (LCE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Perceptual and Cognitive Neuroscience (PCN), Clinical Cognitive Neuropsychiatry Research Program (CCNP), APH - Mental Health, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Adult Psychiatry, Psychiatry, Stochastic Operations Research, Statistics, Germeys, Inez, and van Winkel, Ruud

Subjects
Male, cognition, Proband, DEVELOPMENTAL TRAJECTORIES, SDG 3 – Goede gezondheid en welzijn, 1ST-EPISODE SCHIZOPHRENIA, SYNDROME SCALE PANSS, 0302 clinical medicine, DEFICITS, Models, Psychotic Disorders/classification, Medicine, Longitudinal Studies, psychosis, LIFE-SPAN, Cognition, Statistical, Multinomial logistic regression analysis, Psychiatry and Mental health, Schizophrenia, Female, Original Article, Clinical psychology, Adult, Psychosis, CORRELATED RESPONSES, Endophenotypes, 1ST EPISODE, Young Adult, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Humans, Cognitive Dysfunction, In patient, Effects of sleep deprivation on cognitive performance, cognitive impairment, CLUSTER-ANALYSIS, Schizophrenia/classification, Models, Statistical, business.industry, Siblings, Original Articles, medicine.disease, 030227 psychiatry, schizophrenia, Psychotic Disorders, Endophenotype, Cognitive Dysfunction/classification, business, 030217 neurology & neurosurgery
Abstract

OBJECTIVE: This study aimed to assess the heterogeneity and stability of cognition in patients with a non-affective psychotic disorder and their unaffected siblings. In addition, we aimed to predict the cognitive subtypes of siblings by their probands. METHOD: Assessments were conducted at baseline, 3 and 6 years in 1119 patients, 1059 siblings and 586 controls from the Genetic Risk and Outcome of Psychosis (GROUP) study. Group-based trajectory modeling was applied to identify trajectories and clustered multinomial logistic regression analysis was used for prediction modeling. A composite score of eight neurocognitive tests was used to measure cognitive performance. RESULTS: Five stable cognitive trajectories ranging from severely altered to high cognitive performance were identified in patients. Likewise, four stable trajectories ranging from moderately altered to high performance were found in siblings. Siblings had a higher risk of cognitive alteration when patients' alteration was mild (OR = 2.21), moderate (OR = 5.70), and severe (OR = 10.07) compared with patients with intact cognitive function. The familial correlation coefficient between pairs of index patients and their siblings was 0.27 (P = 0.003). CONCLUSIONS: The cognitive profiles identified in the current study might be suitable as endophenotypes and could be used in future genetic studies and predicting functional and clinical outcomes. ispartof: Acta Psychiatrica Scandinavica vol:138 issue:6 pages:591-604 ispartof: location:United States status: published

Published
2018
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8. Transdiagnostic dimensions of psychopathology at first episode psychosis: findings from the multinational EU-GEI study

Author

Quattrone, Diego, Di Forti, Marta, Gayer-Anderson, Charlotte, Ferraro, Laura, Jongsma, Hannah E, Tripoli, Giada, La Cascia, Caterina, La Barbera, Daniele, Tarricone, Ilaria, Berardi, Domenico, Szöke, Andrei, Arango, Celso, Lasalvia, Antonio, Tortelli, Andrea, Llorca, Pierre-Michel, De Haan, Lieuwe, Velthorst, Eva, Bobes, Julio, Bernardo, Miguel, Sanjuán, Julio, Santos, Jose Luis, Arrojo, Manuel, Del-Ben, Cristina Marta, Menezes, Paulo Rossi, Selten, Jean-Paul, EU-GEI WP2 Group, Jones, Peter B, Kirkbride, James B, Richards, Alexander L, O'Donovan, Michael C, Sham, Pak C, Vassos, Evangelos, Rutten, Bart Pf, Van Os, Jim, Morgan, Craig, Lewis, Cathryn M, Murray, Robin M, Reininghaus, Ulrich, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Psychiatry Department, Adolescent Unit, Hospital General Universitario Gregorio Marañón, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Department of Psychiatry, Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM)-University of Oviedo, Instituto de Engenharia de Sistemas e Computadores Investigação e Desenvolvimento em Lisboa (INESC-ID), Instituto Superior Técnico, Universidade Técnica de Lisboa (IST)-Instituto de Engenharia de Sistemas e Computadores (INESC), Cardiff University, Institute of Psychological Medicine and Clinical Neurosciences, University Medical Center [Utrecht], MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University-Medical Research Council, King‘s College London, Quattrone, Diego, Di Forti, Marta, Gayer-Anderson, Charlotte, Ferraro, Laura, Jongsma, Hannah E, Tripoli, Giada, La Cascia, Caterina, La Barbera, Daniele, Tarricone, Ilaria, Berardi, Domenico, Szoke, Andrei, Arango, Celso, Lasalvia, Antonio, Tortelli, Andrea, Llorca, Pierre-Michel, de Haan, Lieuwe, Velthorst, Eva, Bobes, Julio, Bernardo, Miguel, Sanjuan, Julio, Santos, Jose Lui, Arrojo, Manuel, Del-Ben, Cristina Marta, Menezes, Paulo Rossi, Selten, Jean-Paul, Jones, Peter B., Kirkbride, James B., Richards, Alexander L., O'Donovan, Michael C., Sham, Pak C., Vassos, Evangelo, Rutten, Bart P.F., Os, Jim van, Morgan, Craig, Lewis, Cathryn M., Murray, Robin M., Reininghaus, Ulrich, Quattrone, Diego [0000-0002-6051-8309], Apollo - University of Cambridge Repository, APH - Mental Health, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Adult Psychiatry, Szöke, Andrei, Sanjuán, Julio, Jones, Peter B, Kirkbride, James B, Richards, Alexander L, O'Donovan, Michael C, Sham, Pak C, Rutten, Bart Pf, van Os, Jim, Lewis, Cathryn M, and Murray, Robin M

Subjects
Adult, Affective Disorders, Psychotic, Male, Bipolar Disorder, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Bifactor model, Psicosi, Models, Psychological, symptom dimensions, Pathological psychology, Young Adult, Settore M-PSI/08 - Psicologia Clinica, first episode psychosis, Settore MED/48 -Scienze Infermierist. e Tecn. Neuro-Psichiatriche e Riabilitat, Humans, Settore MED/25 - Psichiatria, ComputingMilieux_MISCELLANEOUS, Psychiatric Status Rating Scales, Psychopathology, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Depression, [SCCO.NEUR]Cognitive science/Neuroscience, Psychoses, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, diagnostic categories, psychopathology, Original Articles, Psicopatologia, Europe, diagnostic categorie, Psychotic Disorders, ROC Curve, first episode psychosi, Schizophrenia, Female, Schizophrenic Psychology, Esquizofrènia
Abstract

Background\ud The value of the nosological distinction between non-affective and affective psychosis has frequently been challenged. We aimed to investigate the transdiagnostic dimensional structure and associated characteristics of psychopathology at First Episode Psychosis (FEP). Regardless of diagnostic categories, we expected that positive symptoms occurred more frequently in ethnic minority groups and in more densely populated environments, and that negative symptoms were associated with indices of neurodevelopmental impairment.\ud \ud Method\ud This study included 2182 FEP individuals recruited across six countries, as part of the EUropean network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Symptom ratings were analysed using multidimensional item response modelling in Mplus to estimate five theory-based models of psychosis. We used multiple regression models to examine demographic and context factors associated with symptom dimensions.\ud \ud Results\ud A bifactor model, composed of one general factor and five specific dimensions of positive, negative, disorganization, manic and depressive symptoms, best-represented associations among ratings of psychotic symptoms. Positive symptoms were more common in ethnic minority groups. Urbanicity was associated with a higher score on the general factor. Men presented with more negative and less depressive symptoms than women. Early age-at-first-contact with psychiatric services was associated with higher scores on negative, disorganized, and manic symptom dimensions.\ud \ud Conclusions\ud Our results suggest that the bifactor model of psychopathology holds across diagnostic categories of non-affective and affective psychosis at FEP, and demographic and context determinants map onto general and specific symptom dimensions. These findings have implications for tailoring symptom-specific treatments and inform research into the mood-psychosis spectrum.

Published
2019
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9. Psychotic Experiences and Related Distress: A Cross-national Comparison and Network Analysis Based on 7141 Participants From 13 Countries

Author

Wusten, Caroline, Schlier, Bjorn, Jaya, Edo S., Alizadeh, Behrooz Z., Bartels-Velthuis, Agna A., van Beveren, Nico J., Bruggeman, Richard, Cahn, Wiepke, de Haan, Lieuwe, Delespaul, Philippe, Meijer, Carin J., Myin-Germeys, Inez, Kahn, Rene S., Schirmbeck, Frederike, Simons, Claudia J. P., van Haren, Neeltje E., van Os, Jim, van Winkel, Ruud, Fonseca-Pedrero, Eduardo, Peters, Emmanuelle, Verdoux, Helene, Woodward, Todd S., Ziermans, Tim B., Lincoln, Tania M., Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), Psychiatry, Brein en Cognitie (Psychologie, FMG), 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), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)

Subjects
Male, SYMPTOMS, 0302 clinical medicine, Cultural values, Medicine, Young adult, COMMUNITY ASSESSMENT, Psychiatry, Aged, 80 and over, GENERAL-POPULATION, RISK, education.field_of_study, cross-cultural comparison, Middle Aged, DEPRESSION, CAPE, high-risk status, Psychiatry and Mental health, Distress, Schizophrenia, Female, epidemiology, Life Sciences & Biomedicine, Clinical psychology, Adult, endocrine system, DIMENSIONS, Cross national comparison, Adolescent, Population, Positive correlation, 03 medical and health sciences, Young Adult, Humans, education, network approach, Developing Countries, psychosis continuum, METAANALYSIS, Aged, CONFIRMATORY FACTOR-ANALYSIS, Science & Technology, business.industry, Developed Countries, medicine.disease, Cross-cultural studies, 030227 psychiatry, culture, body regions, schizophrenia, MODEL, CONTINUUM, Psychotic Disorders, psychosis phenotype, business, human activities, 030217 neurology & neurosurgery, Stress, Psychological, Regular Articles
Abstract

Psychotic experiences (PEs) are common in the general population but do not necessarily reflect a risk status if they occur in relative isolation or are not distressing. Emerging evidence suggests that PEs might be experienced as more benign for individuals from collectivistic low- and middle-income countries (LAMIC) compared with individualistic high-income countries (HIC). The aim of this study was to determine whether: (1) self-reported PEs are less distressing in community samples from LAMIC than from HIC; (2) the network of PEs is significantly less connected in a sample from LAMIC than from HIC. Adults from 8 HIC (n = 4669) and 5 LAMIC (n = 2472) were compared. The lifetime frequency of PEs and related distress were assessed with the Community Assessment of Psychic Experiences. We analyzed the associations of PEs with distress and country type. The interconnection of PEs was visualized by a network analysis and tested for differences in global connection strengths. The average endorsement rates of PEs were significantly higher in LAMIC than in HIC (χ2 = 1772.87, P < .01, Φcramer = 0.50). There was a universal positive correlation between higher frequency of PEs and more distress, but the distress levels controlled for frequency were significantly higher in HIC (R2 = 0.11; b = 0.26; SE = 0.01; T = 17.68; P < .001). Moreover, the network of PEs was significantly less connected in LAMIC (S = 0.40, P < .05). The findings indicate that PEs are of less clinical relevance in LAMIC compared with HIC. The universal use of current high-risk criteria might thus not be adequate without consideration of associated distress and cultural values.

Published
2018
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10. Subjective quality of life in psychosis: Evidence for an association with real world functioning?

Author

Leendertse, Pien, Myin-Germeys, Inez, Lataster, Tineke, Simons, Claudia J P, Oorschot, Margreet, Lardinois, Mariëlle, Schneider, Maude, van Os, Jim, Reininghaus, Ulrich, Alizadeh, Berhooz Z, Bartels-Velthuis, Agna A, Van Beveren, Nico J, Bruggeman, Richard, Cahn, Wiepke, de Haan, Lieuwe, Delespaul, Phillipe, Meijer, Carin J, Kahn, Rene S, Schirmbeck, Frederike, van Haren, Neeltje E, van Winkel, Ruud, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Promovendi MHN, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), APH - Mental Health, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Adult Psychiatry, Other departments, 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), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)

Subjects
Adult, Male, Experience sampling method, Activities of daily living, SYMPTOMS, STRESS, Ecological validity, Ecological Momentary Assessment, Emotions, Affect (psychology), 03 medical and health sciences, Young Adult, 0302 clinical medicine, Quality of life, Recall bias, Activities of Daily Living, SCHIZOPHRENIA, medicine, Journal Article, Humans, Interpersonal Relations, Real life experiences, Biological Psychiatry, RISK, PSYCHOPATHOLOGY, Momentary quality of life, medicine.disease, Social Participation, Experience sampling, humanities, REACTIVITY, 030227 psychiatry, TIME, Affect, Psychiatry and Mental health, INDIVIDUALS, Psychotic Disorders, Schizophrenia, Case-Control Studies, Multivariate Analysis, Quality of Life, Female, Self Report, Psychology, 030217 neurology & neurosurgery, Psychopathology, Clinical psychology
Abstract

Subjective quality of life (SQOL) is an established patient-reported outcome in psychosis. However, current self-report measures of SQOL may be affected by recall bias and may not fully capture dynamic changes in SQOL over time. This study aimed to examine the ecological validity of self-reported and momentary assessment measures of SQOL, and their association with emotional experience, social interaction and activity in real life, in both patients with psychotic disorder (n = 56) and controls (n = 71). Self-reported QOL was assessed with the WHO-QOL, momentary QOL and real life experiences were assessed with the Experience Sampling Method (ESM). Results show that both measures were significantly associated in patients and controls, and associations with emotional experience were most relevant, momentary QOL being a stronger predictor than self-reported QOL. The association between momentary QOL and negative affect was stronger in patients than in controls. Overall, momentary QOL was more consistently associated with affect, social interaction and activity, while self-reported QOL displayed a more narrow association with mostly affect. Concluding, concurrent assessment of self-reported QOL and momentary QOL showed that momentary QOL may enhance the ecological validity of SQOL measurement. Experience sampling research may broaden our perspective on SQOL and its associations with real life functioning.

Published
2018
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11. Child Maltreatment and Clinical Outcome in Individuals at Ultra-High Risk for Psychosis in the EU-GEI High Risk Study

Author

Kraan, Tamar C., Velthorst, Eva, Themmen, Manouk, Valmaggia, Lucia, Kempton, Matthew J., McGuire, Phillip, Van Os, Jim, Rutten, Bart P.F., Smit, Filip, De Haan, Lieuwe, Van Der Gaag, Mark, McGuire, Philip, Valmaggia, Lucia R., Calem, Maria, Tognin, Stefania, Modinos, Gemma, Burger, Nadine, Van Dam, Daniella S., Barrantes-Vidal, Neus, Domínguez-Martínez, Tecelli, Cristóbal-Narváez, Paula, Kwapil, Thomas R., Monsonet-Bardají, Manel, Hinojosa, Lídia, Riecher-Rössler, Anita, Borgwardt, Stefan, Rapp, Charlotte, Ittig, Sarah, Studerus, Erich, Smieskova, Renata, Bressan, Rodrigo, Gadelha, Ary, Brietzke, Elisa, Asevedo, Graccielle, Asevedo, Elson, Zugman, Andre, Ruhrmann, Stephan, Gebhard, Dominika, Arnhold, Julia, Klosterkötter, Joachim, Nordholm, Dorte, Randers, Lasse, Krakauer, Kristine, Naumann, Tanya Louise, Glenthøj, Louise Birkedal, Nordentoft, Merete, De Hert, Marc, Van Winkel, Ruud, Nelson, Barnaby, McGorry, Patrick, Clinical Psychology, APH - Mental Health, RS: MHeNs - R2 - Mental Health, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Adult Psychiatry, and Epidemiology and Data Science

Subjects
Male, Child abuse, INCREASES, clinical outcome, Poison control, Stress Disorders, Post-Traumatic, 0302 clinical medicine, Risk Factors, SCHIZOPHRENIA, Child Abuse, psychosis, Psychological abuse, ultra high risk, Adult Survivors of Child Abuse, PSYCHOPATHOLOGY, Justice and Strong Institutions, Europe, Psychiatry and Mental health, Schizophrenia, Panic Disorder, Female, Psychology, TRANSITION, Psychopathology, Clinical psychology, Adult, medicine.medical_specialty, Psychosis, SDG 16 - Peace, LIFE EVENTS, Adolescent, DISORDERS, Young Adult, 03 medical and health sciences, medicine, Humans, COHORT, Risk factor, Psychiatry, METAANALYSIS, Depressive Disorder, Panic disorder, SDG 16 - Peace, Justice and Strong Institutions, Phobia, Social, medicine.disease, 030227 psychiatry, CONVERSION, Psychotic Disorders, child maltreatment, TRAUMATIC EXPERIENCES, 030217 neurology & neurosurgery, Regular Articles, Follow-Up Studies
Abstract

Background: Child maltreatment has been associated with a wide range of mental disorders in adulthood. Whether child maltreatment is specifically associated with psychosis risk in individuals at ultra-high risk (UHR) for psychosis, or leads to a general vulnerability for overall psychopathology in the UHR stage remains unclear. The present study examines the association between child maltreatment and transition to psychosis and other mental disorders. Methods: The sample consisted of 259 UHR individuals from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study. Participants were followed-up for 2 years to assess clinical outcome. Clinical outcome was assessed at 6 months, 12 months, and 24 months after baseline. Child maltreatment before the age of 17 years was assessed at baseline. Results: Our findings show that a history of emotional abuse was associated with an increased risk for transition to psychosis (OR = 3.78, 95% CI = 1.17 to 12.39, P = -027). Apart from psychosis, a history of physical abuse was associated with depressive disorder (OR = 4.92, 95% CI = 2.12 to 11.39, P = .001), post-traumatic stress disorder (OR = 2.06, 95% CI = 1.10 to 3.86, P = .023), panic disorder (OR = 2.00, 95% CI = 1.00 to 3.99, P = .048) and social phobia (OR = 2.47, 95% CI = 1.18 to 5.16, P = .016) at follow-up. Conclusion: Our findings suggest that in the UHR stage child maltreatment is a pluripotent risk factor for developing psychosis, depressive disorder, post-traumatic stress disorder (PTSD), panic disorder, and social phobia in adulthood.

Published
2017
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12. The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia

Author

Richards, Alexander L, Pardiñas, Antonio F, Frizzati, Aura, Tansey, Katherine E, Lynham, Amy J, Holmans, Peter, Legge, Sophie E, Savage, Jeanne E, Agartz, Ingrid, Andreassen, Ole A, Blokland, Gabriella AM, Corvin, Aiden, Cosgrove, Donna, Degenhardt, Franziska, Djurovic, Srdjan, Espeseth, Thomas, Ferraro, Laura, Gayer-Anderson, Charlotte, Giegling, Ina, van Haren, Neeltje E, Hartmann, Annette M, Hubert, John J, Jönsson, Erik G, Konte, Bettina, Lennertz, Leonhard, Olde Loohuis, Loes M, Melle, Ingrid, Morgan, Craig, Morris, Derek W, Murray, Robin M, Nyman, Håkan, Ophoff, Roel A, GROUP Investigators, van Os, Jim, EUGEI WP2 Group, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Petryshen, Tracey L, Quattrone, Diego, Rietschel, Marcella, Rujescu, Dan, Rutten, Bart PF, Streit, Fabian, Strohmaier, Jana, Sullivan, Patrick F, Sundet, Kjetil, Wagner, Michael, Escott-Price, Valentina, Owen, Michael J, Donohoe, Gary, O'Donovan, Michael C, and Walters, James TR

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

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

Published
2020

13. The EUropean Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) - Incidence and Case-Control Programme

Author

Gayer-Anderson, Charlotte, Jongsma, Hannah E., Di Forti, Marta, Quattrone, Diego, Velthorst, Eva, Haan, Lieuwe de, Selten, Jean Paul, Szöke, Andrei, Llorca, Pierre Michel, Tortelli, Andrea Tortelli, Arango, Celso, Bobes García, Julio, Bernardo Arroyo, Miquel, Sanjuán, Julio, Santos, José Luis, Arrojo, Manuel, Parellada, Mara, Tarricone, Ilaria, Berardi, Domenico, Ruggeri, Mirella, Lasalvia, Antonio, Ferraro, Laura, Cascia, Caterina La, Barbera, Daniele La, Menezes, Paulo Rossi, Ben, Cristina Marta Del, EU-GEI WP2 Group, Rutten, Bart P., van Os, Jim, Jones, Peter B., Murray, Robin M., Kirkbride, James B., and Morgan, Craig

Subjects
Psicosi, Schizophrenia, Psychoses, Esquizofrènia
Abstract

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

Published
2020

14. Association of Adverse Outcomes With Emotion Processing and Its Neural Substrate in Individuals at Clinical High Risk for Psychosis

Author

Modinos, Gemma, Kempton, Matthew J, Tognin, Stefania, Calem, Maria, Porffy, Lilla, Antoniades, Mathilde, Mason, Ava, Azis, Matilda, Allen, Paul, Nelson, Barnaby, McGorry, Patrick, Pantelis, Christos, Riecher-Rossler, Anita, Borgwardt, Stefan, Bressan, Rodrigo, Barrantes-Vidal, Neus, Krebs, Marie-Odile, Nordentoft, Merete, Glenthoj, Birte, Ruhrmann, Stephan, Sachs, Gabriele, Rutten, Bart, van Os, Jim, de Haan, Lieuwe, Velthorst, Eva, van der Gaag, Mark, Valmaggia, Lucia R, McGuire, Philip, Kraan, Tamar C, van Dam, Daniella S, Burger, Nadine, Amminger, G Paul, Politis, Athena, Goodall, Joanne, Rapp, Charlotte, Ittig, Sarah, Studerus, Erich, Smieskova, Renata, Gadelha, Ary, Brietzke, Elisa, Asevedo, Graccielle, Asevedo, Elson, Zugman, Andre, Dominguez-Martinez, Tecelli, Monsonet, Manel, Hinojosa, Lidia, Racioppi, Anna, Kwapil, Thomas R, Kazes, Mathilde, Daban, Claire, Bourgin, Julie, Gay, Olivier, Mam-Lam-Fook, Celia, Nordholm, Dorte, Randers, Lasse, Krakauer, Kristine, Glenthoj, Louise Birkedal, Gebhard, Dominika, Arnhold, Julia, Klosterkotter, Joachim, Lasser, Iris, Winklbaur, Bernadette, Delespaul, Philippe A, MUMC+: MA Psychiatrie (3), Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience, RS: MHeNs - R2 - Mental Health, Adult Psychiatry, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, King‘s College London, University of Roehampton, United Kingdom, University of Melbourne, University of Copenhagen = Københavns Universitet (KU), University of Basel (Unibas), Universidade Federal de São Paulo-Escola Paulista de Medicina [Brazil] (UNIFESP-EPM), Universitat Autònoma de Barcelona (UAB), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), University of Cologne, Medizinische Universität Wien = Medical University of Vienna, Maastricht University [Maastricht], University Medical Center [Utrecht], Amsterdam UMC, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Vrije Universiteit Amsterdam [Amsterdam] (VU), Parnassia Psychiatric Institute [The Hague], South London and Maudsley NHS Foundation Trust, EU-GEI High Risk Study Group, University of Copenhagen = Københavns Universitet (UCPH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Amsterdam UMC - Amsterdam University Medical Center, Martinez Rico, Clara, and Clinical Psychology

Subjects
Male, Global Assessment of Functioning, Emotions, Psychological intervention, FEARFUL FACES, PREFRONTAL CORTEX, 0302 clinical medicine, SCHIZOPHRENIA, Young adult, Gray Matter, Emotional Intelligence, Psychiatry, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Socioemotional selectivity theory, Brain, Magnetic Resonance Imaging, NEUTRAL FACES, 3. Good health, Psychiatry and Mental health, SOCIAL COGNITION, Female, Life Sciences & Biomedicine, Facial Recognition, Clinical psychology, Psychosis, longitudinal, Bipolar disorder, Neuroimaging, functioning, 03 medical and health sciences, Young Adult, medicine, trajectories, Humans, GRAY-MATTER VOLUME, METAANALYSIS, Psychiatric Status Rating Scales, Science & Technology, business.industry, Case-control study, RECOGNITION, prediction, medicine.disease, 030227 psychiatry, Psychotic Disorders, ULTRA-HIGH RISK, Case-Control Studies, ONSET, business, Insula, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Ajuts: Project is funded by grant agreement HEALTH-F2-2010-241909 (Project EU-GEI) from the European Community Seventh Framework Programme. Additional financial support was obtained from the Institut National de la Santé et de la Recherche Médicale (recurrent funding and fellowships) and by Fondation Pierre Deniker. The study received grant 08-MNP-007 from the French government Agence Nationale de la Recherche and grant AOM-07-118 (Influence of Cannabis Psychopathological Outcome in At-risk Mental State [ICAAR study]) from the French Health Ministry Programme Hospitalier de Recherche Clinique. The Sainte-Anne Hospital Center promoted the study. Dr Kempton was supported by a Medical Research Council Fellowship grant MR/J008915/1. Dr Pantelis was supported by Australia's National Health and Medical Research Council Senior Principal Research Fellowship (ID: 628386 & 1105825) and by grant R246-2016-3237 from the Lundbeck Foundation. Dr Barrantes-Vidal was supported by the Ministerio de Ciencia, Innovación e Universidades (PSI2017-87512-C2-1-R), and the Generalitat de Catalunya (2017SGR1612 and ICREA Academia Award). Dr Modinos was supported by a Sir Henry Dale Fellowship #202397/Z/16/Z, jointly funded by The Wellcome Trust and the Royal Society. This case-control study analyzes emotion recognition and neuroimaging data as well as clinical and functional outcomes for individuals at risk for transition to psychosis and those without psychiatric or neurological disorders. Is altered emotion recognition associated with adverse clinical and functional outcomes in people at clinical high risk for psychosis? In this case-control study of 213 individuals at clinical high risk for psychosis and 52 healthy participants, abnormalities in the recognition of negative emotion at baseline were associated with neuroanatomical alterations in the medial prefrontal cortex and hippocampus and with a low level of functioning at a 12-month follow-up. This study found that, in people with high risk for developing psychosis, functional outcomes are associated with the degree to which their emotion processing is altered. The development of adverse clinical outcomes in patients with psychosis has been associated with behavioral and neuroanatomical deficits related to emotion processing. However, the association between alterations in brain regions subserving emotion processing and clinical outcomes remains unclear. To examine the association between alterations in emotion processing and regional gray matter volumes in individuals at clinical high risk (CHR) for psychosis, and the association with subsequent clinical outcomes. This naturalistic case-control study with clinical follow-up at 12 months was conducted from July 1, 2010, to August 31, 2016, and collected data from 9 psychosis early detection centers (Amsterdam, Basel, Cologne, Copenhagen, London, Melbourne, Paris, The Hague, and Vienna). Participants (213 individuals at CHR and 52 healthy controls) were enrolled in the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) project. Data were analyzed from October 1, 2018, to April 24, 2019. Emotion recognition was assessed with the Degraded Facial Affect Recognition Task. Three-Tesla magnetic resonance imaging scans were acquired from all participants, and gray matter volume was measured in regions of interest (medial prefrontal cortex, amygdala, hippocampus, and insula). Clinical outcomes at 12 months were evaluated for transition to psychosis using the Comprehensive Assessment of At-Risk Mental States criteria, and the level of overall functioning was measured through the Global Assessment of Functioning [GAF] scale. A total of 213 individuals at CHR (105 women [49.3%]; mean [SD] age, 22.9 [4.7] years) and 52 healthy controls (25 women [48.1%]; mean [SD] age, 23.3 [4.0] years) were included in the study at baseline. At the follow-up within 2 years of baseline, 44 individuals at CHR (20.7%) had developed psychosis and 169 (79.3%) had not. Of the individuals at CHR reinterviewed with the GAF, 39 (30.0%) showed good overall functioning (GAF score, ≥65), whereas 91 (70.0%) had poor overall functioning (GAF score

Published
2019
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15. Evidence for Genetic Overlap Between Schizophrenia and Age at First Birth in Women

Author

Mehta, Divya, Tropf, Felix C, Gratten, Jacob, Bakshi, Andrew, Zhu, Zhihong, Bacanu, Silviu-Alin, Hemani, Gibran, Magnusson, Patrik KE, Barban, Nicola, Esko, Tõnu, Metspalu, Andres, Snieder, Harold, Mowry, Bryan J, Kendler, Kenneth S, Yang, Jian, Visscher, Peter M, McGrath, John J, Mills, Melinda C, Wray, Naomi R, Lee, S Hong, Schizophrenia Working Group of the Psychiatric Genomics Consortium, LifeLines Cohort Study, and TwinsUK, Andreassen, Ole A, Bramon, Elvira, Bruggeman, Richard, Buxbaum, Joseph D, Cairns, Murray J, Cantor, Rita M, Cloninger, C Robert, Cohen, David, Crespo-Facorro, Benedicto, Darvasi, Ariel, DeLisi, Lynn E, Dinan, Timothy, Djurovic, Srdjan, Donohoe, Gary, Drapeau, Elodie, Escott-Price, Valentina, Freimer, Nelson B, Georgieva, Lyudmila, de Haan, Lieuwe, Henskens, Frans A, Joa, Inge, Julià, Antonio, Khrunin, Andrey, Lerer, Bernard, Limborska, Svetlana, Loughland, Carmel M, Macek, Milan, Marsal, Sara, McCarley, Robert W, McIntosh, Andrew M, McQuillin, Andrew, Melegh, Bela, Michie, Patricia T, Morris, Derek W, Murphy, Kieran C, Myin-Germeys, Inez, Olincy, Ann, Van Os, Jim, Pantelis, Christos, Posthuma, Danielle, Quested, Digby, Schall, Ulrich, Scott, Rodney J, Seidman, Larry J, Toncheva, Draga, Tooney, Paul A, Waddington, John, Weinberger, Daniel R, Weiser, Mark, and Wu, Jing Qin

Subjects
Risk, Adult, Denmark, Cohort Studies, Pregnancy, Clinical Research, Genetics, Humans, Psychology, Genetic Predisposition to Disease, Alleles, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Other Medical and Health Sciences, Prevention, Human Genome, and TwinsUK, Serious Mental Illness, Brain Disorders, Phenotype, Mental Health, Schizophrenia, Female, Cognitive Sciences, Birth Order, LifeLines Cohort Study, Maternal Age, Genome-Wide Association Study
Abstract

ImportanceA recently published study of national data by McGrath et al in 2014 showed increased risk of schizophrenia (SCZ) in offspring associated with both early and delayed parental age, consistent with a U-shaped relationship. However, it remains unclear if the risk to the child is due to psychosocial factors associated with parental age or if those at higher risk for SCZ tend to have children at an earlier or later age.ObjectiveTo determine if there is a genetic association between SCZ and age at first birth (AFB) using genetically informative but independently ascertained data sets.Design, setting, and participantsThis investigation used multiple independent genome-wide association study data sets. The SCZ sample comprised 18 957 SCZ cases and 22 673 controls in a genome-wide association study from the second phase of the Psychiatric Genomics Consortium, and the AFB sample comprised 12 247 genotyped women measured for AFB from the following 4 community cohorts: Estonia (Estonian Genome Center Biobank, University of Tartu), the Netherlands (LifeLines Cohort Study), Sweden (Swedish Twin Registry), and the United Kingdom (TwinsUK). Schizophrenia genetic risk for each woman in the AFB community sample was estimated using genetic effects inferred from the SCZ genome-wide association study.Main outcomes and measuresWe tested if SCZ genetic risk was a significant predictor of response variables based on published polynomial functions that described the relationship between maternal age and SCZ risk in offspring in Denmark. We substituted AFB for maternal age in these functions, one of which was corrected for the age of the father, and found that the fit was superior for the model without adjustment for the father's age.ResultsWe observed a U-shaped relationship between SCZ risk and AFB in the community cohorts, consistent with the previously reported relationship between SCZ risk in offspring and maternal age when not adjusted for the age of the father. We confirmed that SCZ risk profile scores significantly predicted the response variables (coefficient of determination R2 = 1.1E-03, P = 4.1E-04), reflecting the published relationship between maternal age and SCZ risk in offspring by McGrath et al in 2014.Conclusions and relevanceThis study provides evidence for a significant overlap between genetic factors associated with risk of SCZ and genetic factors associated with AFB. It has been reported that SCZ risk associated with increased maternal age is explained by the age of the father and that de novo mutations that occur more frequently in the germline of older men are the underlying causal mechanism. This explanation may need to be revised if, as suggested herein and if replicated in future studies, there is also increased genetic risk of SCZ in older mothers.

Published
2016

16. Association between schizophrenia and common variation in neurocan (NCAN), a genetic risk factor for bipolar disorder

Author

Mühleisen, Thomas W, Mattheisen, Manuel, Rivandeneira, Fernando, Hofman, Albert, Uitterlinden, André G, Moebus, Susanne, Gieger, Christian, Emeny, Rebecca, Ladwig, Karl-Heinz, Wichmann, H-Erich, Schwarz, Markus, Kammerer-Ciernioch, Jutta, Strohmaier, Jana, Schlösser, Ralf G M, Nenadic, Igor, Sauer, Heinrich, Mössner, Rainald, Maier, Wolfgang, Rujescu, Dan, Lange, Christoph, Ophoff, Roel A, Schulze, Thomas G, Rietschel, Marcella, Degenhardt, Franziska, Nöthen, Markus M, Priebe, Lutz, Schultz, C Christoph, Kahn, René S, Linszen, Don H, van Os, Jim, Wiersma, Durk, Bruggeman, Richard, Cahn, Wiepke, de Haan, Lieuwe, Krabbendam, Lydia, Myin-Germeys, Inez, Breuer, René, Wichmann, H -Erich, Breuer, Rene, Meier, Sandra, Hoffmann, Per, Cichon, Sven, Investigators, GROUP, Psychiatrie & Neuropsychologie, RS: MHeNs School for Mental Health and Neuroscience, Adult Psychiatry, Amsterdam Neuroscience, Epidemiology, and Internal Medicine

Subjects
Oncology, NCAN protein, human, medicine.medical_specialty, Bipolar Disorder, Genotype, Psychotic disorder, Medizin, Genetic overlap, Genome-wide association study, Nerve Tissue Proteins, Polymorphism, Single Nucleotide, Hippocampus, Association, 03 medical and health sciences, 0302 clinical medicine, Gene Frequency, Neurocan, Internal medicine, Genetic variation, mental disorders, medicine, Humans, genetics [Schizophrenia], Genetic Predisposition to Disease, Lectins, C-Type, ddc:610, Bipolar disorder, Risk factor, genetics [Nerve Tissue Proteins], Biological Psychiatry, genetics [Lectins, C-Type], 030304 developmental biology, Genetics, genetics [Chondroitin Sulfate Proteoglycans], 0303 health sciences, Case-control study, Odds ratio, medicine.disease, Psychiatry and Mental health, Manic depression, Chondroitin Sulfate Proteoglycans, Schizophrenia, Case-Control Studies, Cortex, Psychology, genetics [Bipolar Disorder], 030217 neurology & neurosurgery
Abstract

A recent study found genome-wide significant association between common variation in the gene neurocan (NCAN, rs1064395) and bipolar disorder (BD). In view of accumulating evidence that BD and schizophrenia partly share genetic risk factors, we tested this single-nucleotide polymorphism for association with schizophrenia in three independent patient-control samples of European ancestry, totaling 5061 patients and 9655 controls. The rs1064395 A-allele, which confers risk for BD, was significantly over-represented in schizophrenia patients compared to controls (p=2.28x10(-3); odds ratio=1.11). Follow-up in non-overlapping samples from the Schizophrenia Psychiatric GWAS Consortium (5537 patients, 8043 controls) provided further support for our finding (p=0.0239, odds ratio=1.07). Our data suggest that genetic variation in NCAN is a common risk factor for BD and schizophrenia. (C) 2012 Elsevier B.V. All rights reserved.

Published
2012
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17. Neuroticism and facial emotion recognition in healthy adults

Author

Andric, Sanja, Maric, Nadja P., Knezevic, Goran, Mihaljevic, Marina, Mirjanic, Tijana, Velthorst, Eva, van Os, Jim, Adult Psychiatry, RS: MHeNs - R2 - Mental Health, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), and Psychiatrie & Neuropsychologie

Subjects
facial emotion recognition, mental disorders, neuroticism, healthy adult
Abstract

Aim The aim of the present study was to examine whether healthy individuals with higher levels of neuroticism, a robust independent predictor of psychopathology, exhibit altered facial emotion recognition performance. MethodsFacial emotion recognition accuracy was investigated in 104 healthy adults using the Degraded Facial Affect Recognition Task (DFAR). Participants' degree of neuroticism was estimated using neuroticism scales extracted from the Eysenck Personality Questionnaire and the Revised NEO Personality Inventory. ResultsA significant negative correlation between the degree of neuroticism and the percentage of correct answers on DFAR was found only for happy facial expression (significant after applying Bonferroni correction). ConclusionsAltered sensitivity to the emotional context represents a useful and easy way to obtain cognitive phenotype that correlates strongly with inter-individual variations in neuroticism linked to stress vulnerability and subsequent psychopathology. Present findings could have implication in early intervention strategies and staging models in psychiatry.

Published
2016

18. Longitudinal association between cognitive performance and obsessive-compulsive symptoms in patients with psychosis and unaffected siblings

Author

Schirmbeck, F., Swets, M., Meijer, C. J., Zink, M., de Haan, L., Kahn, Rene S., Cahn, Wiepke, de Haan, Lieuwe, Meijer, Carin J., van Os, Jim, Myin-Germeys, Inez, Bruggeman, Richard, Bartels-Velthuis, Agna A., Adult Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Graduate School, Other departments, Perceptual and Cognitive Neuroscience (PCN), Clinical Cognitive Neuropsychiatry Research Program (CCNP), RS: MHeNs - R2 - Mental Health, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), and Psychiatrie & Neuropsychologie

Subjects
cognition, DISORDER, Adult, Male, Psychosis, medicine.medical_specialty, Obsessive-Compulsive Disorder, SAMPLE, Adolescent, obsessive-compulsive, Comorbidity, NEUROPSYCHOLOGY, 03 medical and health sciences, Executive Function, Young Adult, 0302 clinical medicine, medicine, Humans, Cognitive skill, Effects of sleep deprivation on cognitive performance, psychosis, Longitudinal Studies, Risk factor, Psychiatry, SCALE, METAANALYSIS, RISK, INSTRUMENT, Recall, Siblings, Neuropsychology, Cognition, Middle Aged, medicine.disease, 030227 psychiatry, PREVALENCE, schizophrenia, MODEL, Psychiatry and Mental health, Cross-Sectional Studies, Psychotic Disorders, Schizophrenia, Mental Recall, Female, Psychology, Cognition Disorders, 030217 neurology & neurosurgery, Psychomotor Performance
Abstract

ObjectiveObsessive-compulsive symptoms (OCS) frequently occur in psychotic disorders. Cross-sectional associations between OCS and cognitive impairment have led to different causal explanations. Whereas one assumes that higher cognitive impairment reflects a risk factor for psychotic patients to develop OCS, another suggests that deficits reflect a consequence of OCS. This study investigated the longitudinal interrelation between OCS and cognitive functioning.MethodBaseline and follow-up data from 622 patients and 670 un-affected siblings from the Genetic Risk and Outcome in Psychosis' study were analyzed. Participants were allocated to groups according to the presence or absence of OCS at assessments and compared on several cognitive domains.ResultsCross-sectional comparisons revealed no group differences in cognitive performance. Longitudinal analyses comparing the groups with changes in OCS revealed one significant group effect with more problems in set-shifting abilities in patient who reported OCS development at follow-up. Significant time and interaction effects were mainly due to improvement in immediate verbal recall and digit-symbol coding in patients and siblings who reported remission of OCS.ConclusionAlthough insight into causality needs further exploration, our results do not confirm the hypothesis of pre-existing cognitive risk constellations. Findings suggest that remission of comorbid OCS results in improved immediate verbal recall and processing speed.

Published
2015

19. Evidence that interactive effects of COMT and MTHFR moderate psychotic response to environmental stress

Author

Peerbooms, O., Rutten, B.P.F., Collip, D., Lardinois, M., Lataster, T., Thewissen, V., Mafi Rad, S., Drukker, M., Kenis, G., van Os, Jim, Myin-Germeys, Inez, van Winkel, Ruud, Psychiatrie & Neuropsychologie, and RS: MHeNs School for Mental Health and Neuroscience

Subjects
epistasis, Adult, Male, Polymorphism, Genetic, Genotype, epigenesis, psychotic disorder, Middle Aged, Resilience, Psychological, Catechol O-Methyltransferase, stress, Gene Frequency, Psychotic Disorders, Case-Control Studies, Adaptation, Psychological, Humans, Female, environment, Methylenetetrahydrofolate Reductase (NADPH2), Stress, Psychological
Abstract

Objective: A functional interaction between Catechol-O-Methyltransferase (COMT) Val158Met and methylenetetrahydrofolate reductase (MTHFR) C677T has been shown to differentially affect cognition in patients with schizophrenia and healthy controls; the effect of COMT Val158Met x MTHFR interaction on resilience to stress in patients and controls remains to be examined. Method: A total of 98 patients with non-affective psychotic disorder and 118 controls were genotyped for MTHFR C677T, MTHFR A1298C, and COMTVal158Met. Daily life reactivity to stress, modelled as the effect of daily life stress on psychotic experiences, was measured using the experience sampling method (ESM). Results: The MTHFR C677T genotype moderated the interaction between COMT Val158Met genotype and stress in patients (P

Published
2011
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20. The relationship between cognitive dysfunction and stress sensitivity in schizophrenia

Author

Morrens, Manuel, Krabbendam, Lydia, Bak, Maarten, Delespaul, Philippe, Mengelers, Ron, Sabbe, Bernard, Hulstijn, Wouter, van Os, Jim, and Myin-Germeys, Inez

Subjects
Action, intention, and motor control, Perception, Action and Control [DI-BCB_DCC_Theme 2]
Abstract

Contains fulltext : 56017.pdf (Publisher’s version ) (Closed access) The aim of the current study was to replicate the finding that cognitive impairments are not or inversely associated with sensitivity to stress in a sample of 25 patients diagnosed with psychotic disorder. The results indicated that impairments in performance on the Trailmaking Test and the Stroop Color Word Test were inversely associated with sensitivity to stress in daily life, whereas impairment in a subtest of the Behavioral Assessment of Dysexecutive Syndrome (BADS) was not associated with stress-sensitivity. The data thus show that in some instances cognitive functioning is not, and in other instances is inversely associated with momentary sensitivity to stress. Cognitive impairment and affective reactivity thus appear to be independent or mutually exclusive mechanisms in psychosis, suggesting competing causal pathways. 4 p.

Published
2007

21. Deconstructing Psychosis

Author

van Os, Jim and Tamminga, Carol

Subjects
Theme: Deconstructing Psychosis Guest Editors: Carol Tamminga and Jim van Os, Psychiatry and Mental health, Psychotic Disorders, Humans
Published
2007
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22. Daily use of high-potency cannabis is associated with more positive symptoms in first-episode psychosis patients: the EU-GEI case-control study

Author

Quattrone, Diego, Ferraro, Laura, Tripoli, Giada, La Cascia, Caterina, Quigley, Harriet, Quattrone, Andrea, Jongsma, Hannah E, Del Peschio, Simona, Gatto, Giusy, EU-GEI Group, Gayer-Anderson, Charlotte, Jones, Peter B, Kirkbride, James B, La Barbera, Daniele, Tarricone, Ilaria, Berardi, Domenico, Tosato, Sarah, Lasalvia, Antonio, Szöke, Andrei, Arango, Celso, Bernardo, Miquel, Bobes, Julio, Del Ben, Cristina Marta, Menezes, Paulo Rossi, Llorca, Pierre-Michel, Santos, Jose Luis, Sanjuán, Julio, Tortelli, Andrea, Velthorst, Eva, De Haan, Lieuwe, Rutten, Bart PF, Lynskey, Michael T, Freeman, Tom P, Sham, Pak C, Cardno, Alastair G, Vassos, Evangelos, Van Os, Jim, Morgan, Craig, Reininghaus, Ulrich, Lewis, Cathryn M, Murray, Robin M, and Di Forti, Marta

Subjects
Marijuana Abuse, Cannabis use, psychopathology, 3. Good health, cannabis-associated psychosis, symptom dimensions, Psychotic Disorders, Case-Control Studies, first episode psychosis, Schizophrenia, Humans, Gene-Environment Interaction, psychotic experiences, Cannabis
Abstract

BACKGROUND: Daily use of high-potency cannabis has been reported to carry a high risk for developing a psychotic disorder. However, the evidence is mixed on whether any pattern of cannabis use is associated with a particular symptomatology in first-episode psychosis (FEP) patients. METHOD: We analysed data from 901 FEP patients and 1235 controls recruited across six countries, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We used item response modelling to estimate two bifactor models, which included general and specific dimensions of psychotic symptoms in patients and psychotic experiences in controls. The associations between these dimensions and cannabis use were evaluated using linear mixed-effects models analyses. RESULTS: In patients, there was a linear relationship between the positive symptom dimension and the extent of lifetime exposure to cannabis, with daily users of high-potency cannabis having the highest score (B = 0.35; 95% CI 0.14-0.56). Moreover, negative symptoms were more common among patients who never used cannabis compared with those with any pattern of use (B = -0.22; 95% CI -0.37 to -0.07). In controls, psychotic experiences were associated with current use of cannabis but not with the extent of lifetime use. Neither patients nor controls presented differences in depressive dimension related to cannabis use. CONCLUSIONS: Our findings provide the first large-scale evidence that FEP patients with a history of daily use of high-potency cannabis present with more positive and less negative symptoms, compared with those who never used cannabis or used low-potency types.

23. Cortical patterning of abnormal morphometric similarity in psychosis is associated with brain expression of schizophrenia-related genes

Author

Morgan, Sarah E, Seidlitz, Jakob, Whitaker, Kirstie J, Romero-Garcia, Rafael, Clifton, Nicholas E, Scarpazza, Cristina, Van Amelsvoort, Therese, Marcelis, Machteld, Van Os, Jim, Donohoe, Gary, Mothersill, David, Corvin, Aiden, Pocklington, Andrew, Raznahan, Armin, McGuire, Philip, Vértes, Petra E, and Bullmore, Edward T

Subjects
Adult, Male, network neuroscience, Allen Human Brain Atlas, Brain, Neuroimaging, Middle Aged, morphometric similarity, 3. Good health, Gene Expression Regulation, Psychotic Disorders, dysconnectivity, Case-Control Studies, Neural Pathways, Schizophrenia, Humans, Female, psychosis, Nerve Net
Abstract

Schizophrenia has been conceived as a disorder of brain connectivity, but it is unclear how this network phenotype is related to the underlying genetics. We used morphometric similarity analysis of MRI data as a marker of interareal cortical connectivity in three prior case-control studies of psychosis: in total, n = 185 cases and n = 227 controls. Psychosis was associated with globally reduced morphometric similarity in all three studies. There was also a replicable pattern of case-control differences in regional morphometric similarity, which was significantly reduced in patients in frontal and temporal cortical areas but increased in parietal cortex. Using prior brain-wide gene expression data, we found that the cortical map of case-control differences in morphometric similarity was spatially correlated with cortical expression of a weighted combination of genes enriched for neurobiologically relevant ontology terms and pathways. In addition, genes that were normally overexpressed in cortical areas with reduced morphometric similarity were significantly up-regulated in three prior post mortem studies of schizophrenia. We propose that this combined analysis of neuroimaging and transcriptional data provides insight into how previously implicated genes and proteins as well as a number of unreported genes in their topological vicinity on the protein interaction network may drive structural brain network changes mediating the genetic risk of schizophrenia.

24. First-Episode Psychosis Patients Who Deteriorated in the Premorbid Period Do Not Have Higher Polygenic Risk Scores Than Others: A Cluster Analysis of EU-GEI Data

Author

Ferraro, L, Quattrone, D, La Barbera, D, La Cascia, C, Morgan, C, Kirkbride, JB, Cardno, AG, Sham, P, Tripoli, G, Sideli, L, Seminerio, F, Sartorio, C, Szoke, A, Tarricone, I, Bernardo, M, Rodriguez, V, Stilo, SA, Gayer-Anderson, C, de Haan, L, Velthorst, E, Jongsma, H, Bart, RBP, Richards, A, Arango, C, Menezez, PR, Lasalvia, A, Tosato, S, Tortelli, A, Del Ben, CM, Selten, J-P, Jones, PB, van Os, J, The WP2 EU-GEI Group, Di Forti, M, Vassos, E, Murray, RM, Adult Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Ferraro, Laura, Quattrone, Diego, La Barbera, Daniele, La Cascia, Caterina, Morgan, Craig, Kirkbride, James B, Cardno, Alastair G, Sham, Pak, Tripoli, Giada, Sideli, Lucia, Seminerio, Fabio, Sartorio, Crocettarachele, Szoke, Andrei, Tarricone, Ilaria, Bernardo, Miquel, Rodriguez, Victoria, Stilo, Simona A, Gayer-Anderson, Charlotte, de Haan, Lieuwe, Velthorst, Eva, Jongsma, Hannah, Bart, Rutten B P, Richards, Alexander, Arango, Celso, Menezez, Paulo Rossi, Lasalvia, Antonio, Tosato, Sarah, Tortelli, Andrea, Del Ben, Cristina Marta, Selten, Jean-Paul, Jones, Peter B, van Os, Jim, Di Forti, Marta, Vassos, Evangelo, Murray, Robin M, Psychiatrie & Neuropsychologie, MUMC+: MA Psychiatrie (3), and RS: MHeNs - R3 - Neuroscience

Subjects
cannabis, cannabi, Adolescent, BIPOLAR DISORDER, ADJUSTMENT, GENE-ENVIRONMENT INTERACTIONS, CLASSIFICATION, bipolar, schizophrenia, Psychiatry and Mental health, Psychotic Disorders, Risk Factors, IQ, ONSET, premorbid, Humans, Cluster Analysis, GENOME-WIDE ASSOCIATION, TRAJECTORIES, deterioration
Abstract

Cluster studies identified a subgroup of patients with psychosis whose premorbid adjustment deteriorates before the onset, which may reflect variation in genetic influence. However, other studies reported a complex relationship between distinctive patterns of cannabis use and cognitive and premorbid impairment that is worthy of consideration. We examined whether: (1) premorbid social functioning (PSF) and premorbid academic functioning (PAF) in childhood and adolescence and current intellectual quotient (IQ) define different clusters in 802 first-episode of psychosis (FEP) patients; resulting clusters vary in (2) polygenic risk scores (PRSs) for schizophrenia (SCZ_PRS), bipolar disorder (BD_PRS), major depression (MD_PRS), and IQ (IQ_PRS), and (3) patterns of cannabis use, compared to 1,263 population-based controls. Four transdiagnostic clusters emerged (BIC = 2268.5): (1) high-cognitive-functioning (n = 205), with the highest IQ (Mean = 106.1, 95% CI: 104.3, 107.9) and PAF, but low PSF. (2) Low-cognitive-functioning (n = 223), with the lowest IQ (Mean = 73.9, 95% CI: 72.2, 75.7) and PAF, but normal PSF. (3) Intermediate (n = 224) (Mean_IQ = 80.8, 95% CI: 79.1, 82.5) with low-improving PAF and PSF. 4) Deteriorating (n = 150) (Mean_IQ = 80.6, 95% CI: 78.5, 82.7), with normal-deteriorating PAF and PSF. The PRSs explained 7.9% of between-group membership. FEP had higher SCZ_PRS than controls [F(4,1319) = 20.4, P

Published
2022
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26. Drug-induced movement disorders in long-stay psychiatric patients : genetic and non-genetic risk factors : a prospective study

Author

Bakker, P.R., van Harten, P.N., van Os, Jim, and RS: FHML non-thematic output

Subjects
movement disorders, anti-psychotics
Abstract

On the site of a psychiatric hospital a man walks with a bent back, slowly with a shaking hand. What is the matter with him? This is one of the movement disorders caused by anti-psychotics. This dissertation shows that movement disorders occur often in this patient group and that therefore prevention is crucial. The hope that the new anti-psychotics would make these horrible side-effects disappear turns out an illusion. Older age and higher anti-psychicum dose are risk factors for certain movement disorders. Analyses of earlier studies suggest multiple genetic influences. Also in additional research weak genetic signals were found that ask for larger long-term random studies, in which the fluctuating course of movement disorders and gene-environment interactions can be included.

Published
2021
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28. The Brain under Attack

Author

Hoffmann, Carolin, Martinez Martinez, Pilar, Rutten, Bart, van Os, Jim, Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience, and Promovendi MHN

Subjects
autoimmunity, psychosis, antibody cloning, autoimmune encephalitis
Abstract

This dissertation investigates the hypothesis whether in a small subgroup of patients with psychotic symptoms, the immune system is attacking the brain. Some autoantibodies have been reported to target specific proteins in the brain and thereby induce neurological and psychotic symptoms. Our results indicate that the presence of these previously described autoantibodies are very rare in the blood of patients with psychotic diagnoses and that the currently used diagnostic methods are of limited use in these cohorts. However, we identified the presence of novel autoantibodies with unclear target in the brain. We further describe two methods to clone autoantibodies from patients immune-cells to be able to produce autoantibodies in the laboratory for further analysis of their pathological function.

Published
2021
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35. Biological mechanisms of environmental stressors in psychiatry : the role of the immune system

Author

Guloksuz, I.S., van Os, Jim, Rutten, Bart, Drukker, Marjan, and RS: MHeNs School for Mental Health and Neuroscience

Subjects
bipolar disorder, immune system, inflammation, depression, environment
Abstract

This thesis aims to better understand the relationships between inflammation and mood disorders. Using molecular approaches on clinical patient groups, this thesis provides further evidence for the role of immune-related pathways in the mechanism of action of lithium for mood stabilization in bipolar disorder and electroconvulsive therapy for treatment-resistant depression. It furthermore has extended the current knowledge about antidepressant effects of infliximab (an anti-inflammatory) in Crohn’s Disease. These novel insights form the next steps showing that immune-related pathways are relevant for the onset and treatment of mood disorders and have the potential to deliver important prognostic information to personalize and optimize treatment.

Published
2021
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36. Mindfulness and aging

Author

Lotte Berk, van Os, Jim, de Vugt, Marjolein, van Boxtel, Martin, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Psychiatrie & Neuropsychologie, and Promovendi MHN

Subjects
Aging, Experience sampling method, mindfulness-based stress reduction, Mindfulness, Relaxation (psychology), Diabetes, Psychological intervention, medicine.disease, Mindfulness-based stress reduction, Mood, Intervention (counseling), medicine, Dementia, Psychology, Clinical psychology
Abstract

The aim of this thesis was to gain insight into the mechanisms of mindfulness in aging individuals, and to investigate whether and how mindfulness is related to mood in daily life. In addition, the application of a mindfulness-based intervention was investigated to support people with dementia and their informal caregivers. Mindfulness or ‘attentiveness’ is a character trait of someone, but also a state that can fluctuate. This research shows that mindfulness is associated with positive effects throughout the day. In addition, our research shows that mindfulness as a character trait is associated with lower-grade inflammation. There was also a lower level of diabetes-related stress in participants with type 2 diabetes with higher levels of mindfulness. The specially developed training ‘AaNDacht’ [EN: attention] for people with dementia and their informal caregivers (TANDEM), was positively received by the participants. The participants indicated that the training helped with relaxation, attention, acceptance and dealing with difficult situations.

Published
2019
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37. Exploring psychosis and multidirectional violence

Author

Steven Honings, van Os, Jim, Drukker, Marjan, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, and Promovendi MHN

Subjects
education.field_of_study, medicine.medical_specialty, Psychosis, Population, social sciences, medicine.disease, Psychotic episodes, violence, trauma, Increased risk, medicine, delusions, psychosis, hallucinations, Psychology, education, Psychiatry, Prospective cohort study
Abstract

Delusions and hallucinations are key symptoms of a psychosis and can occur in people with a psychotic disorder. These individuals also have an increased risk of developing violent tendencies. However, it appears that delusions and hallucinations also occur quite frequently in people with no psychotic disorders. This dissertation examined whether this group runs an equally high risk of developing violent tendencies. It found that people with psychotic episodes are more likely to become violent, both to themselves and to others. They are also more likely to become victims of violence. These results offer new perspectives for preventing violence and psychosis.

Published
2018
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38. Cortical processing of pain

Author

Carine Vossen, Joosten, Bert, van Os, Jim, Lousberg, Henri, MUMC+: MA Anesthesiologie (9), RS: MHeNs - R3 - Neuroscience, Anesthesiologie, and Promovendi MHN

Subjects
medicine.medical_specialty, genetic structures, business.industry, media_common.quotation_subject, Chronic pain, Stimulus (physiology), Hypervigilance, Audiology, medicine.disease, Cortical processing, Pain stimulus, Mood, Medicine, Habituation, medicine.symptom, business, Vigilance (psychology), media_common
Abstract

Pain is a subjective, multidimensional experience that depends on many factors, including pain stimulus intensity, expectations and mood. Compared to questionnaires, pain event-related potentials (pain ERP) allow pain to be evaluated more objectively. Pain ERP means that people receive pain stimuli, for instance electrical stimuli applied to the finger, with simultaneous registration of electrical brain activity. Habituation is an important phenomena following repeated exposure to pain stimuli, describing the progressive decrease of brain signal amplitude. Habituation occurs less in people with chronic pain and is considered a potential key mechanism in the development of chronic pain. Pain hypervigilance, i.e. heightened vigilance for pain sensations, has an impact on pain experience as well. This dissertation examines the relationship between habituation, hypervigilance and chronic pain. We used a new analysis method called the Event-Related Fixed-Interval Area (ERFIA) multilevel method, which not only evaluates ERP peaks, but also examines the pain ERP in closer detail. We showed that stimulus intensity, habituation and hypervigilance had an impact on large sections of the ERP. People with chronic pain showed reduced habituation independent of hypervigilance. Both chronic pain and hypervigilance were independently associated with reduced habituation of the pain ERP. These findings are relevant to the development of future treatment strategies.

Published
2018
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39. Interference of mobile phones with electrophysiology and emotions

Author

Suzanne Roggeveen, van Os, Jim, Lousberg, Henri, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, and Promovendi MHN

Subjects
mobile phone, Potential impact, Brain activity and meditation, Computer science, emotions, Interference (wave propagation), Term (time), radiation, Electrophysiology, Human–computer interaction, Phone, Mobile phone, brain activity, human activities
Abstract

Mobile phones have become an integral part of daily life for most people. This dissertation examines the potential impact of an in-call 3G phone on brain activity and emotions. The results reveal that radiation peaks created by an in-call phone are registered in the brain. There is also an increase in brain activity when someone holds an in-call phone to his or her ear. Mobile phone use is also associated with negative emotions. Further research is required to determine the nature and significance of these connections.

Published
2018
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40. Single transcranial direct current stimulation in schizophrenia: Randomized, cross-over study of neurocognition, social cognition, ERPs, and side effects

Author

Jonathan K. Wynn, Gerhard Hellemann, Yuri Rassovsky, Allan D. Wu, Michael F. Green, Walter Dunn, Marco Iacoboni, and van Os, Jim

Subjects
Male, Social Cognition, 6.6 Psychological and behavioural, Physiology, medicine.medical_treatment, Emotions, lcsh:Medicine, Social Sciences, Electroencephalography, Audiology, Transcranial Direct Current Stimulation, law.invention, 0302 clinical medicine, Cognition, Learning and Memory, Randomized controlled trial, Transcranial Direct-Current Stimulation, law, Medicine and Health Sciences, Psychology, lcsh:Science, Evoked Potentials, Clinical Neurophysiology, Brain Mapping, Multidisciplinary, medicine.diagnostic_test, Transcranial direct-current stimulation, Middle Aged, Electrophysiology, Mental Health, Memory, Short-Term, Bioassays and Physiological Analysis, Brain Electrophysiology, Schizophrenia, Female, Research Article, Adult, medicine.medical_specialty, Adolescent, Social Psychology, General Science & Technology, Imaging Techniques, Cognitive Neuroscience, Clinical Trials and Supportive Activities, Prefrontal Cortex, Neurophysiology, Neuroimaging, Surgical and Invasive Medical Procedures, Research and Analysis Methods, 03 medical and health sciences, Young Adult, Clinical Research, Social cognition, Memory, Mental Health and Psychiatry, medicine, Humans, Working Memory, Social Behavior, Transcranial Stimulation, Functional Electrical Stimulation, Working memory, lcsh:R, Electrophysiological Techniques, Neurosciences, Cognitive Psychology, Evaluation of treatments and therapeutic interventions, Biology and Life Sciences, medicine.disease, Brain Disorders, 030227 psychiatry, Short-Term, Cognitive Science, lcsh:Q, Clinical Medicine, Neurocognitive, 030217 neurology & neurosurgery, Neuroscience
Abstract

Author(s): Rassovsky, Yuri; Dunn, Walter; Wynn, Jonathan K; Wu, Allan D; Iacoboni, Marco; Hellemann, Gerhard; Green, Michael F | Abstract: Over the last decades, the treatment of schizophrenia has shifted fundamentally from a focus on symptom reduction to a focus on recovery and improving aspects of functioning. In this study, we examined the effect of transcranial direct current stimulation (tDCS) on social cognitive and nonsocial neurocognitive functions, as well as on electroencephalogram (EEG) measures, in individuals with schizophrenia. Thirty-seven individuals with schizophrenia were administered one of three different tDCS conditions (cathodal, anodal, and sham) per visit over the course of three visits, with approximately one week between each visit. Order of conditions was randomized and counterbalanced across subjects. For the active conditions, the electrode was placed over the left dorsolateral prefrontal cortex with the reference electrode over right supraorbital cortex. Current intensity was 2 mA and was maintained for two 20-minute sessions, with a one hour break between the sessions. Assessments were conducted immediately following each session, in a counterbalanced order of administration. No systematic effects were found across the social and nonsocial cognitive domains, and no significant effects were detected on event-related potentials (ERPs). The very small effect sizes, further validated by post-hoc power analyses (large Critical Ns), demonstrated that these findings were not due to lack of statistical power. Except for mild local discomfort, no significant side effects were reported. Findings demonstrate the safety and ease of administration of this procedure, but suggest that a single dose of tDCS over these areas does not yield a therapeutic effect on cognition in schizophrenia.Trial registrationClinicalTrials.gov NCT02539797.

Published
2017

41. F115POLYGENIC RISK SCORES FOR SCHIZOPHRENIA, BIPOLAR, AND MAJOR DEPRESSIVE DISORDERS PREDICT TRANSDIAGNOSTIC SYMPTOM DIMENSIONS AT FIRST EPISODE PSYCHOSIS

Author

Victoria Rodriguez, Jim van Os, Cathryn M. Lewis, Bart P. F. Rutten, Robin M. Murray, Alexander Richards, Michael Conlon O'Donovan, Laura Ferraro, Craig Morgan, Diego Quattrone, Giada Tripoli, Marta Di Forti, Pak C. Sham, Evangelos Vassos, Ulrich Reininghaus, Quattrone, Diego, Reininghaus, Ulrich, Vassos, Evangelo, Sham, Pak, Ferraro, Laura, Tripoli, Giada, Rodríguez, Victoria, Morgan, Craig, Van Os, Jim, Rutten, Bart, O'Donovan, Michael, Richards, Alexander, Murray, Robin, Forti, Marta Di, and Lewis, Cathryn

Subjects
Pharmacology, medicine.medical_specialty, business.industry, polygenic, psychosis, spectrum, symptoms, medicine.disease, Psychiatry and Mental health, Neurology, Schizophrenia, First episode psychosis, medicine, Pharmacology (medical), Neurology (clinical), business, Psychiatry, Settore MED/25 - Psichiatria, Biological Psychiatry
Abstract

Background: The value of the nosological distinction between non-affective and affective psychosis has consistently been challenged. Indeed, psychotic syndromes are composed of dimensions of psychopathology cutting across diagnostic boundaries. Such transdiagnostic symptom dimensions might be enhanced phenotypes to test for association with common genetic variants for Major Mental Disorders (MMDs) as summarized by Polygenic Risk Scores (PRSs) for Schizophrenia (SZ), Bipolar Disorder (BP), and Major Depressive Disorder (MDD). The objectives of this study were to: 1) identify the symptom dimension structure at First Episode Psychosis (FEP); 2) examine the extent to which MMDs PRSs explain the phenotypic variance due to symptom dimensions. Methods: OPCRIT psychopathology items were analysed using multidimensional item response modelling in Mplus to estimate unidimensional, multidimensional, and bi-factor models of psychosis. Model fit statistics included LogLikelihood, and Akaike and Bayesian Information Criteria to compare these models. SZ, BP, and MDD PRSs were built using the results from large mega-analyses from the Working Groups of the Psychiatric Genomics Consortium. In PRSice, individuals’ number of risk alleles in the target sample was weighted by the log odds ratio from the discovery samples, and summed into the three PRSs for SZ, BP, and MDD. These PRSs were calculated at a fixed 0.05 P-value SNP threshold. Regression models were fitted to predict symptom dimensions’ scores as continuous outcomes from the three PRSs. These model, conducted in STATA14, were adjusted for age, gender, and 20 principal components for population stratification. Results: The best model fit statistics was observed for the bi-factor model including one general and five specific dimensions of positive, negative, disorganization, manic and depressive symptoms. A positive linear association was observed between SZ PRS and the positive dimension t(789)=2.04, p

Published
2019
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42. Association of Types of Life Events with Depressive Symptoms among Puerto Rican Youth

Author

Sunmin Lee, Xin He, Glorisa Canino, Graciela Jaschek, Olivia Carter-Pokras, and van Os, Jim

Subjects
Male, Coping (psychology), lcsh:Medicine, Social Sciences, Criminology, Social Environment, Adolescents, Families, 0302 clinical medicine, Sociology, Medicine and Health Sciences, Psychology, Longitudinal Studies, Parent-Child Relations, lcsh:Science, Child, Children, Depression (differential diagnoses), Subclinical infection, Multidisciplinary, Schools, Depression, 05 social sciences, Hispanic or Latino, Research Design, Female, Crime, 050104 developmental & child psychology, Research Article, medicine.medical_specialty, Census, Adolescent, General Science & Technology, Protective factor, Psychological Stress, Research and Analysis Methods, Education, Life Change Events, 03 medical and health sciences, Social support, Mental Health and Psychiatry, medicine, Humans, 0501 psychology and cognitive sciences, Adverse effect, Psychiatry, Association (psychology), Violent Crime, Survey Research, business.industry, Mood Disorders, lcsh:R, Puerto Rico, Social environment, Social Support, Biology and Life Sciences, 030227 psychiatry, Age Groups, People and Places, lcsh:Q, New York City, Population Groupings, business
Abstract

Funding for Open Access provided by the UMD Libraries Open Access Publishing Fund., The main objective of this study was to examine the association between four types of adverse life events (family environment, separation, social adversity, and death) and the development of depressive symptoms among Puerto Rican youth. This was a secondary analysis using three waves (2000-2004) of interview data from the Boricua Youth Study of 10-13 year old Puerto Rican youth residing in New York and Puerto Rico with no depressive symptoms at baseline (n = 977). Depressive symptoms increased with an increase in social adversity, separation, death, and death events. Youth support from parents was a significant protective factor for all adverse events and parent coping was a protective factor in social adversity events. Relying on standard diagnostic tools is ideal to identify youth meeting the criteria for a diagnosis of depression but not useful to detect youth who present with subclinical levels of depression. Youth with sub-clinical levels of depression will not get treated and are at increased risk of developing depression later in life. Adverse life events are potentially relevant to use in conjunction with other screening tools to identify Puerto Rican youth who have subclinical depression and are at risk of developing depression in later adolescence.

Published
2015

45. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

Author

Forouzanfar, Mohammad H., Afshin, Ashkan, Alexander, Lily T., Anderson, H. Ross, Bhutta, Zulfiqar A., Biryukov, Stan, Brauer, Michael, Burnett, Richard, Cercy, Kelly, Charlson, Fiona J., Cohen, Aaron J., Dandona, Lalit, Estep, Kara, Ferrari, Alize J., Frostad, Joseph J., Fullman, Nancy, Gething, Peter W., Godwin, William W., Griswold, Max, Hay, Simon I., Kinfu, Yohannes, Kyu, Hmwe H., Larson, Heidi J., Liang, Xiaofeng, Lim, Stephen S., Liu, Patrick Y., Lopez, Alan D., Lozano, Rafael, Marczak, Laurie, Mensah, George A., Mokdad, Ali H., Moradi-Lakeh, Maziar, Naghavi, Mohsen, Neal, Bruce, Reitsma, Marissa B., Roth, Gregory A., Salomon, Joshua A., Sur, Patrick J., Vos, Theo, Wagner, Joseph A., Wang, Haidong, Zhao, Yi, Zhou, Maigeng, Aasvang, Gunn Marit, Abajobir, Amanuel Alemu, Abate, Kalkidan Hassen, Abbafati, Cristiana, Abbas, Kaja M., Abd-Allah, Foad, Abdulle, Abdishakur M., Abera, Semaw Ferede, Abraham, Biju, Abu-Raddad, Laith J., Abyu, Gebre Yitayih, Adebiyi, Akindele Olupelumi, Adedeji, Isaac Akinkunmi, Ademi, Zanfina, Adou, Arsène Kouablan, Adsuar, José C., Agardh, Emilie Elisabet, Agarwal, Arnav, Agrawal, Anurag, Kiadaliri, Aliasghar Ahmad, Ajala, Oluremi N., Akinyemiju, Tomi F., Al-Aly, Ziyad, Alam, Khurshid, Alam, Noore K. M., Aldhahri, Saleh Fahed, Aldridge, Robert William, Alemu, Zewdie Aderaw, Ali, Raghib, Alkerwi, Ala A., Alla, François, Allebeck, Peter, Alsharif, Ubai, Altirkawi, Khalid A., Martin, Elena Alvarez, Alvis-Guzman, Nelson, Amare, Azmeraw T., Amberbir, Alemayehu, Amegah, Adeladza Kofi, Amini, Heresh, Ammar, Walid, Amrock, Stephen Marc, Andersen, Hjalte H., Anderson, Benjamin O., Antonio, Carl Abelardo T., Anwari, Palwasha, Ärnlöv, Johan, Artaman, Al, Asayesh, Hamid, Asghar, Rana Jawad, Assadi, Reza, Atique, Suleman, Avokpaho, Euripide Frinel G. Arthur, Awasthi, Ashish, Quintanilla, Beatriz Paulina Ayala, Azzopardi, Peter, Bacha, Umar, Badawi, Alaa, Bahit, Maria C., Balakrishnan, Kalpana, Barac, Aleksandra, Barber, Ryan M., Barker-Collo, Suzanne L., Bärnighausen, Till, Barquera, Simon, Barregard, Lars, Barrero, Lope H., Basu, Sanjay, Batis, Carolina, Bazargan-Hejazi, Shahrzad, Beardsley, Justin, Bedi, Neeraj, Beghi, Ettore, Bell, Brent, Bell, Michelle L., Bello, Aminu K., Bennett, Derrick A., Bensenor, Isabela M., Berhane, Adugnaw, Bernabé, Eduardo, Betsu, Balem Demtsu, Beyene, Addisu Shunu, Bhala, Neeraj, Bhansali, Anil, Bhatt, Samir, Biadgilign, Sibhatu, Bikbov, Boris, Bisanzio, Donal, Bjertness, Espen, Blore, Jed D., Borschmann, Rohan, Boufous, Soufiane, Bourne, Rupert R. A., Brainin, Michael, Brazinova, Alexandra, Breitborde, Nicholas J. K., Brenner, Hermann, Broday, David M., Brugha, Traolach S., Brunekreef, Bert, Butt, Zahid A., Cahill, Leah E., Calabria, Bianca, Campos-Nonato, Ismael Ricardo, Cárdenas, Rosario, Carpenter, David O., Carrero, Juan Jesus, Casey, Daniel C., Castañeda-Orjuela, Carlos A., Rivas, Jacqueline Castillo, Castro, Ruben Estanislao, Catalá-López, Ferrán, Chang, Jung-Chen, Chiang, Peggy Pei-Chia, Chibalabala, Mirriam, Chimed-Ochir, Odgerel, Chisumpa, Vesper Hichilombwe, Chitheer, Abdulaal A., Choi, Jee-Young Jasmine, Christensen, Hanne, Christopher, Devasahayam Jesudas, Ciobanu, Liliana G., Coates, Matthew M., Colquhoun, Samantha M., Manzano, Alejandra G. Contreras, Cooper, Leslie Trumbull, Cooperrider, Kimberly, Cornaby, Leslie, Cortinovis, Monica, Crump, John A., Cuevas-Nasu, Lucia, Damasceno, Albertino, Dandona, Rakhi, Darby, Sarah C., Dargan, Paul I., Das Neves, José, Davis, Adrian C., Davletov, Kairat, Castro, E. Filipa, La Cruz-Góngora, Vanessa, Leo, Diego, Degenhardt, Louisa, Del Gobbo, Liana C., Del Pozo-Cruz, Borja, Dellavalle, Robert P., Deribew, Amare, Jarlais, Don C. Des, Dharmaratne, Samath D., Dhillon, Preet K., Diaz-Torné, Cesar, Dicker, Daniel, Ding, Eric L., Dorsey, E. Ray, Doyle, Kerrie E., Driscoll, Tim R., Duan, Leilei, Dubey, Manisha, Duncan, Bruce Bartholow, Elyazar, Iqbal, Endries, Aman Yesuf, Ermakov, Sergey Petrovich, Erskine, Holly E., Eshrati, Babak, Esteghamati, Alireza, Fahimi, Saman, Faraon, Emerito Jose Aquino, Farid, Talha A., Farinha, Carla Sofia E. Sa, Faro, André, Farvid, Maryam S., Farzadfar, Farshad, Feigin, Valery L., Fereshtehnejad, Seyed-Mohammad, Fernandes, Jefferson G., Fischer, Florian, Fitchett, Joseph R. A., Fleming, Tom, Foigt, Nataliya, Foreman, Kyle, Fowkes, F. Gerry R., Franklin, Richard C., Fürst, Thomas, Futran, Neal D., Gakidou, Emmanuela, Garcia-Basteiro, Alberto L., Gebrehiwot, Tsegaye Tewelde, Gebremedhin, Amanuel Tesfay, Geleijnse, Johanna M., Gessner, Bradford D., Giref, Ababi Zergaw, Giroud, Maurice, Gishu, Melkamu Dedefo, Giussani, Giorgia, Goenka, Shifalika, Gomez-Cabrera, Mari Carmen, Gomez-Dantes, Hector, Gona, Philimon, Goodridge, Amador, Gopalani, Sameer Vali, Gotay, Carolyn C., Goto, Atsushi, Gouda, Hebe N., Gugnani, Harish Chander, Guillemin, Francis, Guo, Yuming, Gupta, Rahul, Gupta, Rajeev, Gutiérrez, Reyna A., Haagsma, Juanita A., Hafezi-Nejad, Nima, Haile, Demewoz, Hailu, Gessessew Bugssa, Halasa, Yara A., Hamadeh, Randah Ribhi, Hamidi, Samer, Handal, Alexis J., Hankey, Graeme J., Hao, Yuantao, Harb, Hilda L., Harikrishnan, Sivadasanpillai, Haro, Josep Maria, Hassanvand, Mohammad Sadegh, Hassen, Tahir Ahmed, Havmoeller, Rasmus, Heredia-Pi, Ileana Beatriz, Hernández-Llanes, Norberto Francisco, Heydarpour, Pouria, Hoek, Hans W., Hoffman, Howard J., Horino, Masako, Horita, Nobuyuki, Hosgood, H. Dean, Hoy, Damian G., Hsairi, Mohamed, Htet, Aung Soe, Hu, Guoqing, Huang, John J., Husseini, Abdullatif, Hutchings, Sally J., Huybrechts, Inge, Iburg, Kim Moesgaard, Idrisov, Bulat T., Ileanu, Bogdan Vasile, Inoue, Manami, Jacobs, Troy A., Jacobsen, Kathryn H., Jahanmehr, Nader, Jakovljevic, Mihajlo B., Jansen, Henrica A. F. M., Jassal, Simerjot K., Javanbakht, Mehdi, Jayaraman, Sudha P., Jayatilleke, Achala Upendra, Jee, Sun Ha, Jeemon, Panniyammakal, Jha, Vivekanand, Jiang, Ying, Jibat, Tariku, Jin, Ye, Johnson, Catherine O., Jonas, Jost B., Kabir, Zubair, Kalkonde, Yogeshwar, Kamal, Ritul, Kan, Haidong, Karch, André, Karema, Corine Kakizi, Karimkhani, Chante, Kasaeian, Amir, Kaul, Anil, Kawakami, Norito, Kazi, Dhruv S., Keiyoro, Peter Njenga, Kemmer, Laura, Kemp, Andrew Haddon, Kengne, Andre Pascal, Keren, Andre, Kesavachandran, Chandrasekharan Nair, Khader, Yousef Saleh, Khan, Abdur Rahman, Khan, Ejaz Ahmad, Khan, Gulfaraz, Khang, Young-Ho, Khatibzadeh, Shahab, Khera, Sahil, Khoja, Tawfik Ahmed Muthafer, Khubchandani, Jagdish, Kieling, Christian, Kim, Cho-Il, Kim, Daniel, Kimokoti, Ruth W., Kissoon, Niranjan, Kivipelto, Miia, Knibbs, Luke D., Kokubo, Yoshihiro, Kopec, Jacek A., Koul, Parvaiz A., Koyanagi, Ai, Kravchenko, Michael, Kromhout, Hans, Krueger, Hans, Ku, Tiffany, Defo, Barthelemy Kuate, Kuchenbecker, Ricardo S., Bicer, Burcu Kucuk, Kuipers, Ernst J., Kumar, G. Anil, Kwan, Gene F., Lal, Dharmesh Kumar, Lalloo, Ratilal, Lallukka, Tea, Lan, Qing, Larsson, Anders, Latif, Asma Abdul, Lawrynowicz, Alicia Elena Beatriz, Leasher, Janet L., Leigh, James, Leung, Janni, Levi, Miriam, Li, Xiaohong, Li, Yichong, Liang, Juan, Liu, Shiwei, Lloyd, Belinda K., Logroscino, Giancarlo, Lotufo, Paulo A., Lunevicius, Raimundas, Macintyre, Michael, Mahdavi, Mahdi, Majdan, Marek, Majeed, Azeem, Malekzadeh, Reza, Malta, Deborah Carvalho, Manamo, Wondimu Ayele Ayele, Mapoma, Chabila C., Marcenes, Wagner, Martin, Randall V., Martinez-Raga, Jose, Masiye, Felix, Matsushita, Kunihiro, Matzopoulos, Richard, Mayosi, Bongani M., Mcgrath, John J., Mckee, Martin, Meaney, Peter A., Medina, Catalina, Mehari, Alem, Mejia-Rodriguez, Fabiola, Mekonnen, Alemayehu B., Melaku, Yohannes Adama, Memish, Ziad A., Mendoza, Walter, Mensink, Gert B. M., Meretoja, Atte, Meretoja, Tuomo J., Mesfin, Yonatan Moges, Mhimbira, Francis Apolinary, Millear, Anoushka, Miller, Ted R., Mills, Edward J., Mirarefin, Mojde, Misganaw, Awoke, Mock, Charles N., Mohammadi, Alireza, Mohammed, Shafiu, Mola, Glen Liddell D., Monasta, Lorenzo, Hernandez, Julio Cesar Montañez, Montico, Marcella, Morawska, Lidia, Mori, Rintaro, Mozaffarian, Dariush, Mueller, Ulrich O., Mullany, Erin, Mumford, John Everett, Murthy, Gudlavalleti Venkata Satyanarayana, Nachega, Jean B., Naheed, Aliya, Nangia, Vinay, Nassiri, Nariman, Newton, John N., Ng, Marie, Nguyen, Quyen Le, Nisar, Muhammad Imran, Pete, Patrick Martial Nkamedjie, Norheim, Ole F., Norman, Rosana E., Norrving, Bo, Nyakarahuka, Luke, Obermeyer, Carla Makhlouf, Ogbo, Felix Akpojene, Oh, In-Hwan, Oladimeji, Olanrewaju, Olivares, Pedro R., Olsen, Helen, Olusanya, Bolajoko Olubukunola, Olusanya, Jacob Olusegun, Opio, John Nelson, Oren, Eyal, Orozco, Ricardo, Ortiz, Alberto, Ota, Erika, Pa, Mahesh, Pana, Adrian, Park, Eun-Kee, Parry, Charles D., Parsaeian, Mahboubeh, Patel, Tejas, Caicedo, Angel J. Paternina, Patil, Snehal T., Patten, Scott B., Patton, George C., Pearce, Neil, Pereira, David M., Perico, Norberto, Pesudovs, Konrad, Petzold, Max, Phillips, Michael Robert, Piel, Frédéric B., Pillay, Julian David, Plass, Dietrich, Polinder, Suzanne, Pond, Constance D., Pope, C. Arden, Pope, Daniel, Popova, Svetlana, Poulton, Richie G., Pourmalek, Farshad, Prasad, Noela M., Qorbani, Mostafa, Rabiee, Rynaz H. S., Amir Radfar, Rafay, Anwar, Rahimi-Movaghar, Vafa, Rahman, Mahfuzar, Rahman, Mohammad Hifz Ur, Rahman, Sajjad Ur, Rai, Rajesh Kumar, Rajsic, Sasa, Raju, Murugesan, Ram, Usha, Rana, Saleem M., Ranganathan, Kavitha, Rao, Puja, García, Christian Aspacia Razo, Refaat, Amany H., Rehm, Colin D., Rehm, Jürgen, Reinig, Nikolas, Remuzzi, Giuseppe, Resnikoff, Serge, Ribeiro, Antonio L., Rivera, Juan A., Roba, Hirbo Shore, Rodriguez, Alina, Rodriguez-Ramirez, Sonia, Rojas-Rueda, David, Roman, Yesenia, Ronfani, Luca, Roshandel, Gholamreza, Rothenbacher, Dietrich, Roy, Ambuj, Saleh, Muhammad Muhammad, Sanabria, Juan R., Sanchez-Riera, Lidia, Sanchez-Niño, Maria Dolores, Sánchez-Pimienta, Tania G., Sandar, Logan, Santomauro, Damian F., Santos, Itamar S., Sarmiento-Suarez, Rodrigo, Sartorius, Benn, Satpathy, Maheswar, Savic, Miloje, Sawhney, Monika, Schmidhuber, Josef, Schmidt, Maria Inês, Schneider, Ione J. C., Schöttker, Ben, Schutte, Aletta E., Schwebel, David C., Scott, James G., Seedat, Soraya, Sepanlou, Sadaf G., Servan-Mori, Edson E., Shaddick, Gavin, Shaheen, Amira, Shahraz, Saeid, Shaikh, Masood Ali, Levy, Teresa Shamah, Sharma, Rajesh, She, Jun, Sheikhbahaei, Sara, Shen, Jiabin, Sheth, Kevin N., Shi, Peilin, Shibuya, Kenji, Shigematsu, Mika, Shin, Min-Jeong, Shiri, Rahman, Shishani, Kawkab, Shiue, Ivy, Shrime, Mark G., Sigfusdottir, Inga Dora, Silva, Diego Augusto Santos, Silveira, Dayane Gabriele Alves, Silverberg, Jonathan I., Simard, Edgar P., Sindi, Shireen, Singh, Abhishek, Singh, Jasvinder A., Singh, Prashant Kumar, Slepak, Erica Leigh, Soljak, Michael, Soneji, Samir, Sorensen, Reed J. D., Sposato, Luciano A., Sreeramareddy, Chandrashekhar T., Stathopoulou, Vasiliki, Steckling, Nadine, Steel, Nicholas, Stein, Dan J., Stein, Murray B., Stöckl, Heidi, Stranges, Saverio, Stroumpoulis, Konstantinos, Sunguya, Bruno F., Swaminathan, Soumya, Sykes, Bryan L., Szoeke, Cassandra E. I., Tabarés-Seisdedos, Rafael, Takahashi, Ken, Talongwa, Roberto Tchio, Tandon, Nikhil, Tanne, David, Tavakkoli, Mohammad, Taye, Belaynew Wasie, Taylor, Hugh R., Tedla, Bemnet Amare, Tefera, Worku Mekonnen, Tegegne, Teketo Kassaw, Tekle, Dejen Yemane, Terkawi, Abdullah Sulieman, Thakur, J. S., Thomas, Bernadette A., Thomas, Matthew Lloyd, Thomson, Alan J., Thorne-Lyman, Andrew L., Thrift, Amanda G., Thurston, George D., Tillmann, Taavi, Tobe-Gai, Ruoyan, Tobollik, Myriam, Topor-Madry, Roman, Topouzis, Fotis, Towbin, Jeffrey Allen, Tran, Bach Xuan, Dimbuene, Zacharie Tsala, Tsilimparis, Nikolaos, Tura, Abera Kenay, Tuzcu, Emin Murat, Tyrovolas, Stefanos, Ukwaja, Kingsley N., Undurraga, Eduardo A., Uneke, Chigozie Jesse, Uthman, Olalekan A., Donkelaar, Aaron, Os, Jim, Varakin, Yuri Y., Vasankari, Tommi, Veerman, J. 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Hassanvand, Mohammad Sadegh, Hassen, Tahir Ahmed, Havmoeller, Rasmu, Heredia-Pi, Ileana Beatriz, Hernández-Llanes, Norberto Francisco, Heydarpour, Pouria, Hoek, Hans W, Hoffman, Howard J, Horino, Masako, Horita, Nobuyuki, Hosgood, H Dean, Hoy, Damian G, Hsairi, Mohamed, Htet, Aung Soe, Hu, Guoqing, Huang, John J, Husseini, Abdullatif, Hutchings, Sally J, Huybrechts, Inge, Iburg, Kim Moesgaard, Idrisov, Bulat T, Ileanu, Bogdan Vasile, Inoue, Manami, Jacobs, Troy A, Jacobsen, Kathryn H, Jahanmehr, Nader, Jakovljevic, Mihajlo B, Jansen, Henrica A F M, Jassal, Simerjot K, Javanbakht, Mehdi, Jayatilleke, Achala Upendra, Jee, Sun Ha, Jeemon, Panniyammakal, Jha, Vivekanand, Jiang, Ying, Jibat, Tariku, Jin, Ye, Johnson, Catherine O, Jonas, Jost B, Kabir, Zubair, Kalkonde, Yogeshwar, Kamal, Ritul, Kan, Haidong, Karch, André, Karema, Corine Kakizi, Karimkhani, Chante, Kasaeian, Amir, Kaul, Anil, Kawakami, Norito, Kazi, Dhruv S, Keiyoro, Peter Njenga, Kemp, Andrew Haddon, Kengne, Andre Pascal, 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Muhammad Imran, Pete, Patrick Martial Nkamedjie, Norheim, Ole F, Norman, Rosana E, Norrving, Bo, Nyakarahuka, Luke, Obermeyer, Carla Makhlouf, Ogbo, Felix Akpojene, Oh, In-Hwan, Oladimeji, Olanrewaju, Olivares, Pedro R, Olsen, Helen, Olusanya, Bolajoko Olubukunola, Olusanya, Jacob Olusegun, Opio, John Nelson, Oren, Eyal, Orozco, Ricardo, Ortiz, Alberto, Ota, Erika, Pa, Mahesh, Pana, Adrian, Park, Eun-Kee, Parry, Charles D, Parsaeian, Mahboubeh, Patel, Teja, Caicedo, Angel J Paternina, Patil, Snehal T, Patten, Scott B, Patton, George C, Pearce, Neil, Pereira, David M, Perico, Norberto, Pesudovs, Konrad, Petzold, Max, Phillips, Michael Robert, Piel, Frédéric B, Pillay, Julian David, Plass, Dietrich, Polinder, Suzanne, Pond, Constance D, Pope, C Arden, Pope, Daniel, Popova, Svetlana, Poulton, Richie G, Pourmalek, Farshad, Prasad, Noela M, Qorbani, Mostafa, Rabiee, Rynaz H S, Radfar, Amir, Rafay, Anwar, Rahimi-Movaghar, Vafa, Rahman, Mahfuzar, Rahman, Mohammad Hifz Ur, Rahman, Sajjad Ur, 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Sara, Shen, Jiabin, Sheth, Kevin N, Shi, Peilin, Shibuya, Kenji, Shigematsu, Mika, Shin, Min-Jeong, Shiri, Rahman, Shishani, Kawkab, Shiue, Ivy, Shrime, Mark G, Sigfusdottir, Inga Dora, Silva, Diego Augusto Santo, Silveira, Dayane Gabriele Alve, Silverberg, Jonathan I, Simard, Edgar P, Sindi, Shireen, Singh, Abhishek, Singh, Jasvinder A, Singh, Prashant Kumar, Slepak, Erica Leigh, Soljak, Michael, Soneji, Samir, Sorensen, Reed J D, Sposato, Luciano A, Sreeramareddy, Chandrashekhar T, Stathopoulou, Vasiliki, Steckling, Nadine, Steel, Nichola, Stein, Dan J, Stein, Murray B, Stöckl, Heidi, Stranges, Saverio, Stroumpoulis, Konstantino, Sunguya, Bruno F, Swaminathan, Soumya, Sykes, Bryan L, Szoeke, Cassandra E I, Tabarés-Seisdedos, Rafael, Takahashi, Ken, Talongwa, Roberto Tchio, Tandon, Nikhil, Tanne, David, Tavakkoli, Mohammad, Taye, Belaynew Wasie, Taylor, Hugh R, Tedla, Bemnet Amare, Tefera, Worku Mekonnen, Tegegne, Teketo Kassaw, Tekle, Dejen Yemane, Terkawi, Abdullah Sulieman, Thakur, J.S., Thomas, Bernadette A, Thomas, Matthew Lloyd, Thomson, Alan J, Thorne-Lyman, Andrew L, Thrift, Amanda G, Thurston, George D, Tillmann, Taavi, Tobe-Gai, Ruoyan, Tobollik, Myriam, Topor-Madry, Roman, Topouzis, Foti, Towbin, Jeffrey Allen, Tran, Bach Xuan, Dimbuene, Zacharie Tsala, Tsilimparis, Nikolao, Tura, Abera Kenay, Tuzcu, Emin Murat, Tyrovolas, Stefano, Ukwaja, Kingsley N, Undurraga, Eduardo A, Uneke, Chigozie Jesse, Uthman, Olalekan A, van Donkelaar, Aaron, van Os, Jim, Varakin, Yuri Y, Vasankari, Tommi, Veerman, J Lennert, Venketasubramanian, Narayanaswamy, Violante, Francesco S, Vollset, Stein Emil, Wagner, Gregory R, Waller, Stephen G, Wang, Jian Li, Wang, Linhong, Wang, Yanping, Weichenthal, Scott, Weiderpass, Elisabete, Weintraub, Robert G, Werdecker, Andrea, Westerman, Ronny, Whiteford, Harvey A, Wijeratne, Tissa, Wiysonge, Charles Shey, Wolfe, Charles D A, Won, Sungho, Woolf, Anthony D, Wubshet, Mamo, Xavier, Deni, Xu, Gelin, Yadav, Ajit Kumar, Yakob, Bereket, Yalew, Ayalnesh Zemene, Yano, Yuichiro, Yaseri, Mehdi, Ye, Pengpeng, Yip, Paul, Yonemoto, Naohiro, Yoon, Seok-Jun, Younis, Mustafa Z, Yu, Chuanhua, Zaidi, Zoubida, Zaki, Maysaa El Sayed, Zhu, Jun, Zipkin, Ben, Zodpey, Sanjay, Zuhlke, Liesl Joanna, Murray, Christopher J L, Public Health, Gastroenterology & Hepatology, Health Services Management & Organisation (HSMO), Psychiatry, Kardiyoloji, RS: MHeNs - R2 - Mental Health, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), and Psychiatrie & Neuropsychologie

Subjects
Blood Glucose, Alcohol Drinking, Global Health, Risk Assessment, Body Mass Index, Middle East, Life Expectancy, Risk-Taking, Africa, Northern, General & Internal Medicine, Quality-Adjusted Life Year, Occupational Exposure, Africa South of the Sahara, Medicine(all), Unsafe Sex, Risk Factor, Medicine (all), Malnutrition, Smoking, Public Health, Global Health, Social Medicine and Epidemiology, Sodium, Dietary, Articles, 11 Medical And Health Sciences, Biomarker, Environmental Exposure, Substance-Related Disorder, Cost of Illne, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Cholesterol, Air Pollution, Indoor, Hypertension, Disabled Person, Human
Abstract

Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors-the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57.8% (95% CI 56.6-58.8) of global deaths and 41.2% (39.8-42.8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211.8 million [192.7 million to 231.1 million] global DALYs), smoking (148.6 million [134.2 million to 163.1 million]), high fasting plasma glucose (143.1 million [125.1 million to 163.5 million]), high BMI (120.1 million [83.8 million to 158.4 million]), childhood undernutrition (113.3 million [103.9 million to 123.4 million]), ambient particulate matter (103.1 million [90.8 million to 115.1 million]), high total cholesterol (88.7 million [74.6 million to 105.7 million]), household air pollution (85.6 million [66.7 million to 106.1 million]), alcohol use (85.0 million [77.2 million to 93.0 million]), and diets high in sodium (83.0 million [49.3 million to 127.5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Copyright (C) The Author(s). Published by Elsevier Ltd.

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