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1. Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations

Author

Stevelink, Remi, Luykx, Jurjen J, Lin, Bochao D, Leu, Costin, Lal, Dennis, Smith, Alexander W, Schijven, Dick, Carpay, Johannes A, Rademaker, Koen, Baldez, Roiza A Rodrigues, Devinsky, Orrin, Braun, Kees PJ, Jansen, Floor E, Smit, Dirk JA, Koeleman, Bobby PC, Abou‐Khalil, Bassel, Auce, Pauls, Avbersek, Andreja, Bahlo, Melanie, Balding, David J, Bast, Thomas, Baum, Larry, Becker, Albert J, Becker, Felicitas, Berghuis, Bianca, Berkovic, Samuel F, Boysen, Katja E, Bradfield, Jonathan P, Brody, Lawrence C, Buono, Russell J, Campbell, Ellen, Cascino, Gregory D, Catarino, Claudia B, Cavalleri, Gianpiero L, Cherny, Stacey S, Chinthapalli, Krishna, Coffey, Alison J, Compston, Alastair, Coppola, Antonietta, Cossette, Patrick, Craig, John J, de Haan, Gerrit‐Jan, De Jonghe, Peter, de Kovel, Carolien GF, Delanty, Norman, Depondt, Chantal, Dlugos, Dennis J, Doherty, Colin P, Elger, Christian E, Eriksson, Johan G, Ferraro, Thomas N, Feucht, Martha, Francis, Ben, Franke, Andre, French, Jacqueline A, Freytag, Saskia, Gaus, Verena, Geller, Eric B, Gieger, Christian, Glauser, Tracy, Glynn, Simon, Goldstein, David B, Gui, Hongsheng, Guo, Youling, Haas, Kevin F, Hakonarson, Hakon, Hallmann, Kerstin, Haut, Sheryl, Heinzen, Erin L, Helbig, Ingo, Hengsbach, Christian, Hjalgrim, Helle, Iacomino, Michele, Ingason, Andrés, Jamnadas‐Khoda, Jennifer, Johnson, Michael R, Kälviäinen, Reetta, Kantanen, Anne‐Mari, Kasperavičiūte, Dalia, Trenite, Dorothee Kasteleijn‐Nolst, Kirsch, Heidi E, Knowlton, Robert C, Krause, Roland, Krenn, Martin, Kunz, Wolfram S, Kuzniecky, Ruben, Kwan, Patrick, Lau, Yu‐Lung, Lehesjoki, Anna‐Elina, Lerche, Holger, Lieb, Wolfgang, Lindhout, Dick, Lo, Warren D, Lopes‐Cendes, Iscia, Lowenstein, Daniel H, Malovini, Alberto, Marson, Anthony G, Mayer, Thomas, McCormack, Mark, and Mills, James L

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Genetics, Brain Disorders, Clinical Research, Human Genome, Neurodegenerative, Epilepsy, 2.1 Biological and endogenous factors, Aetiology, Neurological, Adult, Algorithms, Beta Rhythm, Cohort Studies, Databases, Factual, Electroencephalography, Epilepsy, Generalized, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Mendelian Randomization Analysis, Risk Assessment, Theta Rhythm, beta power, EEG, generalized epilepsy, GGE, oscillations, PRS, International League Against Epilepsy Consortium on Complex Epilepsies, Epi25 Collaborative, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveParoxysmal epileptiform abnormalities on electroencephalography (EEG) are the hallmark of epilepsies, but it is uncertain to what extent epilepsy and background EEG oscillations share neurobiological underpinnings. Here, we aimed to assess the genetic correlation between epilepsy and background EEG oscillations.MethodsConfounding factors, including the heterogeneous etiology of epilepsies and medication effects, hamper studies on background brain activity in people with epilepsy. To overcome this limitation, we compared genetic data from a genome-wide association study (GWAS) on epilepsy (n = 12 803 people with epilepsy and 24 218 controls) with that from a GWAS on background EEG (n = 8425 subjects without epilepsy), in which background EEG oscillation power was quantified in four different frequency bands: alpha, beta, delta, and theta. We replicated our findings in an independent epilepsy replication dataset (n = 4851 people with epilepsy and 20 428 controls). To assess the genetic overlap between these phenotypes, we performed genetic correlation analyses using linkage disequilibrium score regression, polygenic risk scores, and Mendelian randomization analyses.ResultsOur analyses show strong genetic correlations of genetic generalized epilepsy (GGE) with background EEG oscillations, primarily in the beta frequency band. Furthermore, we show that subjects with higher beta and theta polygenic risk scores have a significantly higher risk of having generalized epilepsy. Mendelian randomization analyses suggest a causal effect of GGE genetic liability on beta oscillations.SignificanceOur results point to shared biological mechanisms underlying background EEG oscillations and the susceptibility for GGE, opening avenues to investigate the clinical utility of background EEG oscillations in the diagnostic workup of epilepsy.

Published
2021

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

Author

Fusar-Poli, Laura, Prachason, Thanavadee, Erzin, Gamze, Pries, Lotta-Katrin, Brondino, Natascia, Politi, Pierluigi, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J, Lin, Bochao D, Richards, Alexander L, Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M, Andric-Petrovic, Sanja, Mirjanic, Tijana, Bernardo, Miguel, Mezquida, Gisela, Amoretti, Silvia, Bobes, Julio, Saiz, Pilar A, García-Portilla, Maria Paz, Sanjuan, Julio, Escarti, Maria Jose, Santos, José Luis, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P, Atbaşoğlu, Cem, Üçok, Alp, Alptekin, Köksal, Saka, Meram Can, Arango, Celso, O'Donovan, Michael, van Os, Jim, Rutten, Bart PF, and Guloksuz, Sinan

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

Author

Fusar-Poli, Laura, Pries, Lotta-Katrin, van Os, Jim, Radhakrishnan, Rajiv, Pençe, Ayşegül Yay, Erzin, Gamze, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J, Lin, Bochao D, Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M, Andric-Petrovic, Sanja, Mirjanic, Tijana, Bernardo, Miguel, Mezquida, Gisela, Amoretti, Silvia, Bobes, Julio, Saiz, Pilar A, García-Portilla, Maria Paz, Sanjuan, Julio, Aguilar, Eduardo J, Santos, José Luis, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P, Atbaşoğlu, Cem, Üçok, Alp, Alptekin, Köksal, Saka, Meram Can, Aguglia, Eugenio, Arango, Celso, Rutten, Bart PF, and Guloksuz, Sinan

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

Author

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

Published
2022
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9. Polygenic risk, familial liability and stress reactivity in psychosis: an experience sampling study

Author

Schick, Anita, van Winkel, Ruud, Lin, Bochao D, Luykx, Jurjen J, de Zwarte, Sonja MC, van Eijk, Kristel R, Investigators, Group, Myin-Germeys, Inez, Reininghaus, Ulrich, Psychiatrie & Neuropsychologie, and RS: MHeNs - R2 - Mental Health

Subjects
Psychiatry, MECHANISM, Science & Technology, polygenic risk, stress sensitivity, Psychology, Clinical, ecological momentary assessment, PSYCHOPATHOLOGY, Social Sciences, Digital phenotyping, ASSOCIATION, GENE-ENVIRONMENT INTERACTIONS, gene-environment interaction, CHILDHOOD TRAUMA, Psychiatry and Mental health, DAILY-LIFE, SCHIZOPHRENIA, Psychology, SENSITIVITY, Life Sciences & Biomedicine, PSYCHOLOGICAL PROCESSES, Applied Psychology, SCALE
Abstract

Background There is evidence for a polygenic contribution to psychosis. One targetable mechanism through which polygenic variation may impact on individuals and interact with the social environment is stress sensitization, characterized by elevated reactivity to minor stressors in daily life. The current study aimed to investigate whether stress reactivity is modified by polygenic risk score for schizophrenia (PRS) in cases with enduring non-affective psychotic disorder, first-degree relatives of cases, and controls. Methods We used the experience sampling method to assess minor stressors, negative affect, positive affect and psychotic experiences in 96 cases, 79 first-degree relatives, i.e. siblings, and 73 controls at wave 3 of the Dutch Genetic Risk and Outcome of Psychosis (GROUP) study. Genome-wide data were collected at baseline to calculate PRS. Results We found that associations of momentary stress with psychotic experiences, but not with negative and positive affect, were modified by PRS and group (all pFWEv. low level of PRS. By contrast, controls with high PRS showed more intense psychotic experiences in response to stress compared to those with low PRS. Conclusions This tentatively suggests that polygenic risk may operate in different ways than previously assumed and amplify reactivity to stress in unaffected individuals but operate as a resilience factor in relatives by attenuating their stress reactivity.

Published
2023

10. Associations Between Polygenic Risk Score Loading, Psychosis Liability, and Clozapine Use Among Individuals With Schizophrenia

Author

Lin, Bochao D., Pinzón-Espinosa, Justo, Blouzard, Elodie, Van Der Horst, Marte Z., Okhuijsen-pfeifer, Cynthia, Van Eijk, Kristel R., Guloksuz, Sinan, Peyrot, Wouter J., Luykx, Jurjen J., Hasan, Alkomiet, Wagner, Elias, Pantelis, Christos, Everall, Ian P., Ayhan, Y., Babaoğlu, M. O., Bak, Maarten, Alink, Wouter, Beld, E, Bouhuis, A, Edlinger, M, Erdoğan, I .m., Gutwinski, Stefan, Hallikainen, Tero, Jeger-land, E, Lähteenvuo, Markku, De Koning, Mariken B., Morgenroth, Carla, Müderrisoğlu, A., Oviedo-salcedo, Tatiana, Schreiter, Stefanie, Repo-tiihonen, Eila, Tuppurainen, Heli, Veereschild, Mike, Veerman, Selene R.t., Cohen, Dan, De Vos, M, Bogers, Jan P.a.m., Anıl Yağcıoğlu, A.e., Tiihonen, Jari, Ripke, Stephan, Bousman, Chad A., Van Beek, H, Van Der Horst, Marte, Van Eijk, Kristel, Ertuğrul, A., Yoca, G., Görlitz, T., Grootens, K., Leucht, Stefan, Narang, A., Schneider-thoma, J., Kahn, René S., Bekema, Erwin, Kleymann, Phillip, Alizadeh, Behrooz Z., Van Amelsvoort, Therese, Cahn, Wiepke, De Haan, Lieuwe, Schirmbeck, Frederike, Simons, Claudia J.p., Van Os, Jim, Rutten, Bart, Van Winkel, Ruud, RS: MHeNs - R3 - Neuroscience, RS: MHeNs - R2 - Mental Health, Psychiatry 1, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Geestelijke Gezondheidszorg, Tranzo, Scientific center for care and wellbeing, Psychiatry, APH - Mental Health, and Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep

Subjects
Adult, Psychiatry and Mental health, Schizophrenia/drug therapy, SDG 3 - Good Health and Well-being, Risk Factors, Humans, Female, Antipsychotic Agents/adverse effects, Psychotic Disorders/drug therapy, Multifactorial Inheritance/genetics, Clozapine/adverse effects
Abstract

ImportancePredictors consistently associated with psychosis liability and course of illness in schizophrenia (SCZ) spectrum disorders (SSD), including the need for clozapine treatment, are lacking. Longitudinally ascertained medication use may empower studies examining associations between polygenic risk scores (PRSs) and pharmacotherapy choices.ObjectiveTo examine associations between PRS-SCZ loading and groups with different liabilities to SSD (individuals with SSD taking clozapine, individuals with SSD taking other antipsychotics, their parents and siblings, and unrelated healthy controls) and between PRS-SCZ and the likelihood of receiving a prescription of clozapine relative to other antipsychotics.Design, Setting, and ParticipantsThis genetic association study was a multicenter, observational cohort study with 6 years of follow-up. Included were individuals diagnosed with SSD who were taking clozapine or other antipsychotics, their parents and siblings, and unrelated healthy controls. Data were collected from 2004 until 2021 and analyzed between October 2021 and September 2022.ExposuresPolygenic risk scores for SCZ.Main Outcomes and MeasuresMultinomial logistic regression was used to examine possible differences between groups by computing risk ratios (RRs), ie, ratios of the probability of pertaining to a particular group divided by the probability of healthy control status. We also computed PRS-informed odd ratios (ORs) for clozapine use relative to other antipsychotics.ResultsPolygenic risk scores for SCZ were generated for 2344 participants (mean [SD] age, 36.95 years [14.38]; 994 female individuals [42.4%]) who remained after quality control screening (557 individuals with SSD taking clozapine, 350 individuals with SSD taking other antipsychotics during the 6-year follow-up, 542 parents and 574 siblings of individuals with SSD, and 321 unrelated healthy controls). All RRs were significantly different from 1; RRs were highest for individuals with SSD taking clozapine (RR, 3.24; 95% CI, 2.76-3.81; P = 2.47 × 10−46), followed by individuals with SSD taking other antipsychotics (RR, 2.30; 95% CI, 1.95-2.72; P = 3.77 × 10−22), parents (RR, 1.44; 95% CI, 1.25-1.68; P = 1.76 × 10−6), and siblings (RR, 1.40; 95% CI, 1.21-1.63; P = 8.22 × 10−6). Polygenic risk scores for SCZ were positively associated with clozapine vs other antipsychotic use (OR, 1.41; 95% CI, 1.22-1.63; P = 2.98 × 10−6), suggesting a higher likelihood of clozapine prescriptions among individuals with higher PRS-SCZ.Conclusions and RelevanceIn this study, PRS-SCZ loading differed between groups of individuals with SSD, their relatives, and unrelated healthy controls, with patients taking clozapine at the far end of PRS-SCZ loading. Additionally, PRS-SCZ was associated with a higher likelihood of clozapine prescribing. Our findings may inform early intervention and prognostic studies of the value of using PRS-SCZ to personalize antipsychotic treatment.

Published
2023

11. Genome-wide association meta-analysis of individuals of European ancestry identifies new loci explaining a substantial fraction of hair color variation and heritability

Author

Hysi, Pirro G., Valdes, Ana M., Liu, Fan, Furlotte, Nicholas A., Evans, David M., Bataille, Veronique, Visconti, Alessia, Hemani, Gibran, McMahon, George, Ring, Susan M., Smith, George Davey, Duffy, David L., Zhu, Gu, Gordon, Scott D., Medland, Sarah E., Lin, Bochao D., Willemsen, Gonneke, Jan Hottenga, Jouke, Vuckovic, Dragana, Girotto, Giorgia, Gandin, Ilaria, Sala, Cinzia, Concas, Maria Pina, Brumat, Marco, Gasparini, Paolo, Toniolo, Daniela, Cocca, Massimiliano, Robino, Antonietta, Yazar, Seyhan, Hewitt, Alex W., Chen, Yan, Zeng, Changqing, Uitterlinden, Andre G., Ikram, M. Arfan, Hamer, Merel A., van Duijn, Cornelia M., Nijsten, Tamar, Mackey, David A., Falchi, Mario, Boomsma, Dorret I., Martin, Nicholas G., The International Visible Trait Genetics Consortium, Hinds, David A., Kayser, Manfred, and Spector, Timothy D.

Published
2018
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12. Gene-environment interaction study on the polygenic risk score for neuroticism, childhood adversity, and parental bonding

Author

Hersenen-Medisch 1, Onderzoek, Brain, Klingenberg, Boris, Guloksuz, Sinan, Pries, Lotta Katrin, Cinar, Ozan, Menne-Lothmann, Claudia, Decoster, Jeroen, Van Winkel, Ruud, Collip, Dina, Delespaul, Philippe, De Hert, Marc, Derom, Catherine, Thiery, Evert, Jacobs, Nele, Wichers, Marieke, Lin, Bochao D., Luykx, Jurjen, Van Os, Jim, Rutten, Bart P.F., Hersenen-Medisch 1, Onderzoek, Brain, Klingenberg, Boris, Guloksuz, Sinan, Pries, Lotta Katrin, Cinar, Ozan, Menne-Lothmann, Claudia, Decoster, Jeroen, Van Winkel, Ruud, Collip, Dina, Delespaul, Philippe, De Hert, Marc, Derom, Catherine, Thiery, Evert, Jacobs, Nele, Wichers, Marieke, Lin, Bochao D., Luykx, Jurjen, Van Os, Jim, and Rutten, Bart P.F.

Published
2023

13. Associations Between Polygenic Risk Score Loading, Psychosis Liability, and Clozapine Use Among Individuals With Schizophrenia

Author

Hersenen-Medisch 1, Diagnostiek & Vroege Psychose Medisch, Ontwikkelingsstoornissen Med., Onderzoeksgroep 9, Neurogenetica, Onderzoek, Brain, Lin, Bochao D., Pinzón-Espinosa, Justo, Blouzard, Elodie, Van Der Horst, Marte Z., Okhuijsen-Pfeifer, Cynthia, Van Eijk, Kristel R., Guloksuz, Sinan, Peyrot, Wouter J., Luykx, Jurjen J., Hersenen-Medisch 1, Diagnostiek & Vroege Psychose Medisch, Ontwikkelingsstoornissen Med., Onderzoeksgroep 9, Neurogenetica, Onderzoek, Brain, Lin, Bochao D., Pinzón-Espinosa, Justo, Blouzard, Elodie, Van Der Horst, Marte Z., Okhuijsen-Pfeifer, Cynthia, Van Eijk, Kristel R., Guloksuz, Sinan, Peyrot, Wouter J., and Luykx, Jurjen J.

Published
2023

14. Age- and sex-specific associations between risk scores for schizophrenia and self-reported health in the general population

Author

Hersenen-Medisch 1, Neurogenetica, Brain, Paquin, Vincent, Pries, Lotta-Katrin, Ten Have, Margreet, Bak, Maarten, Gunther, Nicole, de Graaf, Ron, van Dorsselaer, Saskia, Lin, Bochao D, van Eijk, Kristel R, Kenis, Gunter, Richards, Alexander, O'Donovan, Michael C, Luykx, Jurjen J, Rutten, Bart P F, van Os, Jim, Shah, Jai L, Guloksuz, Sinan, Hersenen-Medisch 1, Neurogenetica, Brain, Paquin, Vincent, Pries, Lotta-Katrin, Ten Have, Margreet, Bak, Maarten, Gunther, Nicole, de Graaf, Ron, van Dorsselaer, Saskia, Lin, Bochao D, van Eijk, Kristel R, Kenis, Gunter, Richards, Alexander, O'Donovan, Michael C, Luykx, Jurjen J, Rutten, Bart P F, van Os, Jim, Shah, Jai L, and Guloksuz, Sinan

Published
2023

15. Polygenic risk, familial liability and stress reactivity in psychosis: an experience sampling study

Author

Hersenen-Medisch 1, Onderzoek, Brain, Onderzoeksgroep 1, Neurogenetica, Schick, Anita, van Winkel, Ruud, Lin, Bochao D., Luykx, Jurjen J., de Zwarte, Sonja M.C., van Eijk, Kristel R., Reininghaus, Ulrich, Myin-Germeys, Inez, Hersenen-Medisch 1, Onderzoek, Brain, Onderzoeksgroep 1, Neurogenetica, Schick, Anita, van Winkel, Ruud, Lin, Bochao D., Luykx, Jurjen J., de Zwarte, Sonja M.C., van Eijk, Kristel R., Reininghaus, Ulrich, and Myin-Germeys, Inez

Published
2023

16. Context v. algorithm: Evidence that a transdiagnostic framework of contextual clinical characterization is of more clinical value than categorical diagnosis

Author

Hersenen-Medisch 1, Brain, TN groep Adan, Onderzoek, Neurogenetica, Van Os, Jim, Pries, Lotta Katrin, Ten Have, Margreet, De Graaf, Ron, Van Dorsselaer, Saskia, Bak, Maarten, Kenis, Gunter, Lin, Bochao D., Gunther, Nicole, Luykx, Jurjen J., Rutten, Bart P.F., Guloksuz, Sinan, Hersenen-Medisch 1, Brain, TN groep Adan, Onderzoek, Neurogenetica, Van Os, Jim, Pries, Lotta Katrin, Ten Have, Margreet, De Graaf, Ron, Van Dorsselaer, Saskia, Bak, Maarten, Kenis, Gunter, Lin, Bochao D., Gunther, Nicole, Luykx, Jurjen J., Rutten, Bart P.F., and Guloksuz, Sinan

Published
2023

17. Gene–environment interaction study on the polygenic risk score for neuroticism, childhood adversity, and parental bonding

Author

Klingenberg, Boris, primary, Guloksuz, Sinan, additional, Pries, Lotta-Katrin, additional, Cinar, Ozan, additional, Menne-Lothmann, Claudia, additional, Decoster, Jeroen, additional, van Winkel, Ruud, additional, Collip, Dina, additional, Delespaul, Philippe, additional, De Hert, Marc, additional, Derom, Catherine, additional, Thiery, Evert, additional, Jacobs, Nele, additional, Wichers, Marieke, additional, Lin, Bochao D., additional, Luykx, Jurjen, additional, van Os, Jim, additional, and Rutten, Bart P. F., additional

Published
2023
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18. Age- and sex-specific associations between risk scores for schizophrenia and self-reported health in the general population

Author

Paquin, Vincent, primary, Pries, Lotta-Katrin, additional, ten Have, Margreet, additional, Bak, Maarten, additional, Gunther, Nicole, additional, de Graaf, Ron, additional, van Dorsselaer, Saskia, additional, Lin, Bochao D., additional, van Eijk, Kristel R., additional, Kenis, Gunter, additional, Richards, Alexander, additional, O’Donovan, Michael C., additional, Luykx, Jurjen J., additional, Rutten, Bart P. F., additional, van Os, Jim, additional, Shah, Jai L., additional, and Guloksuz, Sinan, additional

Published
2022
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19. 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

20. A polygenic-informed approach to a predictive EEG signature empowers antidepressant treatment prediction: A proof-of-concept study

Author

AIOS Psychiatrie, Hersenen-Medisch 1, Neurogenetica, Meijs, Hannah, Prentice, Amourie, Lin, Bochao D., De Wilde, Bieke, Van Hecke, Jan, Niemegeers, Peter, van Eijk, Kristel, Luykx, Jurjen J., Arns, Martijn, AIOS Psychiatrie, Hersenen-Medisch 1, Neurogenetica, Meijs, Hannah, Prentice, Amourie, Lin, Bochao D., De Wilde, Bieke, Van Hecke, Jan, Niemegeers, Peter, van Eijk, Kristel, Luykx, Jurjen J., and Arns, Martijn

Published
2022

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

Author

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

Published
2022

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

Author

Hersenen-Medisch 1, Brain, TN groep Adan, Laboranten CT Radiologie, Henquet, Cécile, van Os, Jim, Pries, Lotta K, Rauschenberg, Christian, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J, Lin, Bochao D, Richards, Alexander L, Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem S, Kaymak, Semra U, Mihaljevic, Marina M, Petrovic, Sanja S, Mirjanic, Tijana, Bernardo, Miguel, Mezquida, Gisela, Amoretti, Silvia, Bobes, Julio, Saiz, Pilar A, García-Portilla, Maria P, Sanjuan, Julio, Aguilar, Eduardo J, Santos, Jose L, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P, Atbaşoğlu, Cem, Ucok, Alp, Alptekin, Köksal, Saka, Meram C, Arango, Celso, O'Donovan, Michael, Rutten, Bart P F, Gülöksüz, Sinan, Hersenen-Medisch 1, Brain, TN groep Adan, Laboranten CT Radiologie, Henquet, Cécile, van Os, Jim, Pries, Lotta K, Rauschenberg, Christian, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J, Lin, Bochao D, Richards, Alexander L, Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem S, Kaymak, Semra U, Mihaljevic, Marina M, Petrovic, Sanja S, Mirjanic, Tijana, Bernardo, Miguel, Mezquida, Gisela, Amoretti, Silvia, Bobes, Julio, Saiz, Pilar A, García-Portilla, Maria P, Sanjuan, Julio, Aguilar, Eduardo J, Santos, Jose L, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P, Atbaşoğlu, Cem, Ucok, Alp, Alptekin, Köksal, Saka, Meram C, Arango, Celso, O'Donovan, Michael, Rutten, Bart P F, and Gülöksüz, Sinan

Published
2022

23. Context v. algorithm: evidence that a transdiagnostic framework of contextual clinical characterization is of more clinical value than categorical diagnosis.

Author

van Os, Jim, Pries, Lotta-Katrin, ten Have, Margreet, de Graaf, Ron, van Dorsselaer, Saskia, Bak, Maarten, Kenis, Gunter, Lin, Bochao D., Gunther, Nicole, Luykx, Jurjen J., Rutten, Bart P. F., and Guloksuz, Sinan

Subjects
PSYCHIATRIC diagnosis, ANXIETY diagnosis, MENTAL illness, DIAGNOSIS of mental depression, GENETICS, PSYCHOSES, MENTAL health, INTERVIEWING, CONCEPTUAL structures, SUICIDAL ideation, SYMPTOMS, DESCRIPTIVE statistics, SOCIODEMOGRAPHIC factors, PREDICTION models, CLASSIFICATION of mental disorders, ALGORITHMS, MEDICAL needs assessment, LONGITUDINAL method, FAMILY history (Medicine)
Abstract

Background: A transdiagnostic and contextual framework of 'clinical characterization', combining clinical, psychopathological, sociodemographic, etiological, and other personal contextual data, may add clinical value over and above categorical algorithm-based diagnosis. Methods: Prediction of need for care and health care outcomes was examined prospectively as a function of the contextual clinical characterization diagnostic framework in a prospective general population cohort (n = 6646 at baseline), interviewed four times between 2007 and 2018 (NEMESIS-2). Measures of need, service use, and use of medication were predicted as a function of any of 13 DSM-IV diagnoses, both separately and in combination with clinical characterization across multiple domains: social circumstances/demographics, symptom dimensions, physical health, clinical/etiological factors, staging, and polygenic risk scores (PRS). Effect sizes were expressed as population attributable fractions. Results: Any prediction of DSM-diagnosis in relation to need and outcome in separate models was entirely reducible to components of contextual clinical characterization in joint models, particularly the component of transdiagnostic symptom dimensions (a simple score of the number of anxiety, depression, mania, and psychosis symptoms) and staging (subthreshold, incidence, persistence), and to a lesser degree clinical factors (early adversity, family history, suicidality, slowness at interview, neuroticism, and extraversion), and sociodemographic factors. Clinical characterization components in combination predicted more than any component in isolation. PRS did not meaningfully contribute to any clinical characterization model. Conclusion: A transdiagnostic framework of contextual clinical characterization is of more value to patients than a categorical system of algorithmic ordering of psychopathology. [ABSTRACT FROM AUTHOR]

Published
2023
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24. Publisher Correction: Genome-wide association meta-analysis of individuals of European ancestry identifies new loci explaining a substantial fraction of hair color variation and heritability

Author

Hysi, Pirro G., Valdes, Ana M., Liu, Fan, Furlotte, Nicholas A., Evans, David M., Bataille, Veronique, Visconti, Alessia, Hemani, Gibran, McMahon, George, Ring, Susan M., Smith, George Davey, Duffy, David L., Zhu, Gu, Gordon, Scott D., Medland, Sarah E., Lin, Bochao D., Willemsen, Gonneke, Jan Hottenga, Jouke, Vuckovic, Dragana, Girotto, Giorgia, Gandin, Ilaria, Sala, Cinzia, Concas, Maria Pina, Brumat, Marco, Gasparini, Paolo, Toniolo, Daniela, Cocca, Massimiliano, Robino, Antonietta, Yazar, Seyhan, Hewitt, Alex W., Chen, Yan, Zeng, Changqing, Uitterlinden, Andre G., Ikram, M. Arfan, Hamer, Merel A., van Duijn, Cornelia M., Nijsten, Tamar, Mackey, David A., Falchi, Mario, Boomsma, Dorret I., Martin, Nicholas G., The International Visible Trait Genetics Consortium, Hinds, David A., Kayser, Manfred, and Spector, Timothy D.

Published
2019
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25. Examining the independent and joint effects of molecular genetic liability and environmental exposures in schizophrenia

Author

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

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

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

Published
2019

26. Context v. algorithm: evidence that a transdiagnostic framework of contextual clinical characterization is of more clinical value than categorical diagnosis

Author

van Os, Jim, primary, Pries, Lotta-Katrin, additional, ten Have, Margreet, additional, de Graaf, Ron, additional, van Dorsselaer, Saskia, additional, Bak, Maarten, additional, Kenis, Gunter, additional, Lin, Bochao D., additional, Gunther, Nicole, additional, Luykx, Jurjen J., additional, Rutten, Bart P. F., additional, and Guloksuz, Sinan, additional

Published
2021
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28. What makes the psychosis 'clinical high risk' state risky: psychosis itself or the co-presence of a non-psychotic disorder?

Author

Hersenen-Medisch 1, Brain, Hasmi, Laila, Pries, Lotta-Katrin, Ten Have, Margreet, de Graaf, Ron, van Dorsselaer, Saskia, Bak, Maarten, Kenis, Gunter, Richards, Alexander, Lin, Bochao D, O'Donovan, Michael C, Luykx, Jurjen J, Rutten, Bart P F, Guloksuz, Sinan, van Os, Jim, Hersenen-Medisch 1, Brain, Hasmi, Laila, Pries, Lotta-Katrin, Ten Have, Margreet, de Graaf, Ron, van Dorsselaer, Saskia, Bak, Maarten, Kenis, Gunter, Richards, Alexander, Lin, Bochao D, O'Donovan, Michael C, Luykx, Jurjen J, Rutten, Bart P F, Guloksuz, Sinan, and van Os, Jim

Published
2021

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

Author

van Os, Jim, Pries, Lotta-Katrin, ten Have, Margreet, de Graaf, Ron, van Dorsselaer, Saskia, Delespaul, Philippe, Bak, Maarten, Kenis, Gunter, Lin, Bochao D., Luykx, Jurjen J., Richards, Alexander L., Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, and Cankurtaran, Eylem Şahin

Subjects
SCHIZOPHRENIA risk factors, HALLUCINATIONS, ADVERSE childhood experiences, GENETICS, CHRONOBIOLOGY disorders, PSYCHOSES, INTERVIEWING, MOLECULAR biology, CELLULAR signal transduction, REPLICATION (Experimental design), DESCRIPTIVE statistics, AFFECTIVE disorders, MENTAL depression
Abstract

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

Published
2022
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30. A replication study of JTC bias, genetic liability for psychosis and delusional ideation.

Author

Henquet, Cécile, van Os, Jim, Pries, Lotta K., Rauschenberg, Christian, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J., Lin, Bochao D., Richards, Alexander L., Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem S., Kaymak, Semra U., and Mihaljevic, Marina M.

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

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

Published
2022
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31. Erratum:Associations between psychiatric disorders, COVID-19 testing probability and COVID-19 testing results: Findings from a population-based study (BJPsych Open (2020) 6:5 (e87) DOI: 10.1192/bjo.2020.75)

Author

van der Meer, Dennis, Pinzón-Espinosa, Justo, Lin, Bochao D., Tijdink, Joeri K., Vinkers, Christiaan H., Guloksuz, Sinan, and Luykx, Jurjen J.

Abstract

This article failed to state the coequal contribution to the article of its first two authors, Dennis van der Meer and Justo Pinz n- Espinosa. This note was deleted accidentally during the production process, for which the publisher apologises.

Published
2020

32. A new genetic locus for antipsychotic-induced weight gain:A genome-wide study of first-episode psychosis patients using amisulpride (from the OPTiMiSE cohort)

Author

ter Hark, Sophie E., Jamain, Stéphane, Schijven, Dick, Lin, Bochao D., Bakker, Mark K., Boland-Auge, Anne, Deleuze, Jean François, Troudet, Réjane, Malhotra, Anil K., Gülöksüz, Sinan, Vinkers, Christiaan H., Ebdrup, Bjørn H., Kahn, René S., Leboyer, Marion, Luykx, Jurjen J., ter Hark, Sophie E., Jamain, Stéphane, Schijven, Dick, Lin, Bochao D., Bakker, Mark K., Boland-Auge, Anne, Deleuze, Jean François, Troudet, Réjane, Malhotra, Anil K., Gülöksüz, Sinan, Vinkers, Christiaan H., Ebdrup, Bjørn H., Kahn, René S., Leboyer, Marion, and Luykx, Jurjen J.

Abstract

Background: Antipsychotic-induced weight gain is a common and debilitating side effect of antipsychotics. Although genome-wide association studies of antipsychotic-induced weight gain have been performed, few genome-wide loci have been discovered. Moreover, these genome-wide association studies have included a wide variety of antipsychotic compounds. Aims: We aim to gain more insight in the genomic loci affecting antipsychotic-induced weight gain. Given the variable pharmacological properties of antipsychotics, we hypothesized that targeting a single antipsychotic compound would provide new clues about genomic loci affecting antipsychotic-induced weight gain. Methods: All subjects included for this genome-wide association study (n=339) were first-episode schizophrenia spectrum disorder patients treated with amisulpride and were minimally medicated (defined as antipsychotic use <2 weeks in the previous year and/or <6 weeks lifetime). Weight gain was defined as the increase in body mass index from before until approximately 1 month after amisulpride treatment. Results: Our genome-wide association analyses for antipsychotic-induced weight gain yielded one genome-wide significant hit (rs78310016; β=1.05; p=3.66 × 10−08; n=206) in a locus not previously associated with antipsychotic-induced weight gain or body mass index. Minor allele carriers had an odds ratio of 3.98 (p=1.0 × 10−03) for clinically meaningful antipsychotic-induced weight gain (⩾7% of baseline weight). In silico analysis elucidated a chromatin interaction with 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1. In an attempt to replicate single-nucleotide polymorphisms previously associated with antipsychotic-induced weight gain, we found none were associated with amisulpride-induced weight gain. Conclusion: Our findings suggest the involvement of rs78310016 and possibly 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1 in antipsychotic-induced weight gain. In line with the unique binding p

Published
2020

33. Do Current Measures of Polygenic Risk for Mental Disorders Contribute to Population Variance in Mental Health?

Author

TN groep Adan, Hersenen-Medisch 1, Brain, Marsman, Anne, Pries, Lotta-Katrin, Ten Have, Margreet, de Graaf, Ron, van Dorsselaer, Saskia, Bak, Maarten, Kenis, Gunter, Lin, Bochao D, Luykx, Jurjen J, Rutten, Bart P F, Guloksuz, Sinan, van Os, Jim, TN groep Adan, Hersenen-Medisch 1, Brain, Marsman, Anne, Pries, Lotta-Katrin, Ten Have, Margreet, de Graaf, Ron, van Dorsselaer, Saskia, Bak, Maarten, Kenis, Gunter, Lin, Bochao D, Luykx, Jurjen J, Rutten, Bart P F, Guloksuz, Sinan, and van Os, Jim

Published
2020

34. Association of Recent Stressful Life Events With Mental and Physical Health in the Context of Genomic and Exposomic Liability for Schizophrenia

Author

Hersenen-Medisch 1, Brain, TN groep Adan, Neurogenetica, Pries, Lotta-Katrin, van Os, Jim, Ten Have, Margreet, de Graaf, Ron, van Dorsselaer, Saskia, Bak, Maarten, Lin, Bochao D, van Eijk, Kristel R, Kenis, Gunter, Richards, Alexander, O'Donovan, Michael C, Luykx, Jurjen J, Rutten, Bart P F, Guloksuz, Sinan, Hersenen-Medisch 1, Brain, TN groep Adan, Neurogenetica, Pries, Lotta-Katrin, van Os, Jim, Ten Have, Margreet, de Graaf, Ron, van Dorsselaer, Saskia, Bak, Maarten, Lin, Bochao D, van Eijk, Kristel R, Kenis, Gunter, Richards, Alexander, O'Donovan, Michael C, Luykx, Jurjen J, Rutten, Bart P F, and Guloksuz, Sinan

Published
2020

35. Association of preceding psychosis risk states and non-psychotic mental disorders with incidence of clinical psychosis in the general population: a prospective study in the NEMESIS-2 cohort

Author

Neurogenetica, Brain, Hersenen-Medisch 1, Guloksuz, Sinan, Pries, Lotta Katrin, ten Have, Margreet, de Graaf, Ron, van Dorsselaer, Saskia, Klingenberg, Boris, Bak, Maarten, Lin, Bochao D, van Eijk, Kristel R., Delespaul, Philippe, van Amelsvoort, Therese, Luykx, Jurjen J., Rutten, Bart P.F., van Os, Jim, Neurogenetica, Brain, Hersenen-Medisch 1, Guloksuz, Sinan, Pries, Lotta Katrin, ten Have, Margreet, de Graaf, Ron, van Dorsselaer, Saskia, Klingenberg, Boris, Bak, Maarten, Lin, Bochao D, van Eijk, Kristel R., Delespaul, Philippe, van Amelsvoort, Therese, Luykx, Jurjen J., Rutten, Bart P.F., and van Os, Jim

Published
2020

36. A new genetic locus for antipsychotic-induced weight gain: A genome-wide study of first-episode psychosis patients using amisulpride (from the OPTiMiSE cohort)

Author

Neurogenetica, Brain, TN groep Adan, MS Neonatologie, Onderzoeksgroep 11, Ter Hark, Sophie E, Jamain, Stéphane, Schijven, Dick, Lin, Bochao D, Bakker, Mark K, Boland-Auge, Anne, Deleuze, Jean-François, Troudet, Réjane, Malhotra, Anil K, Gülöksüz, Sinan, Vinkers, Christiaan H, Ebdrup, Bjørn H, Kahn, René S, Leboyer, Marion, Luykx, Jurjen J, Neurogenetica, Brain, TN groep Adan, MS Neonatologie, Onderzoeksgroep 11, Ter Hark, Sophie E, Jamain, Stéphane, Schijven, Dick, Lin, Bochao D, Bakker, Mark K, Boland-Auge, Anne, Deleuze, Jean-François, Troudet, Réjane, Malhotra, Anil K, Gülöksüz, Sinan, Vinkers, Christiaan H, Ebdrup, Bjørn H, Kahn, René S, Leboyer, Marion, and Luykx, Jurjen J

Published
2020

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

Author

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

Published
2020

38. What makes the psychosis ‘clinical high risk’ state risky: psychosis itself or the co-presence of a non-psychotic disorder?

Author

Hasmi, Laila, primary, Pries, Lotta-Katrin, additional, ten Have, Margreet, additional, de Graaf, Ron, additional, van Dorsselaer, Saskia, additional, Bak, Maarten, additional, Kenis, Gunter, additional, Richards, Alexander, additional, Lin, Bochao D., additional, O'Donovan, Michael C., additional, Luykx, Jurjen J., additional, Rutten, Bart P.F., additional, Guloksuz, Sinan, additional, and van Os, Jim, additional

Published
2021
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39. Association of Recent Stressful Life Events With Mental and Physical Health in the Context of Genomic and Exposomic Liability for Schizophrenia

Author

Pries, Lotta-Katrin, primary, van Os, Jim, additional, ten Have, Margreet, additional, de Graaf, Ron, additional, van Dorsselaer, Saskia, additional, Bak, Maarten, additional, Lin, Bochao D., additional, van Eijk, Kristel R., additional, Kenis, Gunter, additional, Richards, Alexander, additional, O’Donovan, Michael C., additional, Luykx, Jurjen J., additional, Rutten, Bart P. F., additional, and Guloksuz, Sinan, additional

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

Author

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

Published
2020
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43. A replication study of JTC bias, genetic liability for psychosis and delusional ideation

Author

Henquet, Cécile, primary, van Os, Jim, additional, Pries, Lotta K., additional, Rauschenberg, Christian, additional, Delespaul, Philippe, additional, Kenis, Gunter, additional, Luykx, Jurjen J., additional, Lin, Bochao D., additional, Richards, Alexander L., additional, Akdede, Berna, additional, Binbay, Tolga, additional, Altınyazar, Vesile, additional, Yalınçetin, Berna, additional, Gümüş-Akay, Güvem, additional, Cihan, Burçin, additional, Soygür, Haldun, additional, Ulaş, Halis, additional, Cankurtaran, Eylem S., additional, Kaymak, Semra U., additional, Mihaljevic, Marina M., additional, Petrovic, Sanja S., additional, Mirjanic, Tijana, additional, Bernardo, Miguel, additional, Mezquida, Gisela, additional, Amoretti, Silvia, additional, Bobes, Julio, additional, Saiz, Pilar A., additional, García-Portilla, Maria P., additional, Sanjuan, Julio, additional, Aguilar, Eduardo J., additional, Santos, Jose L., additional, Jiménez-López, Estela, additional, Arrojo, Manuel, additional, Carracedo, Angel, additional, López, Gonzalo, additional, González-Peñas, Javier, additional, Parellada, Mara, additional, Maric, Nadja P., additional, Atbaşoğlu, Cem, additional, Ucok, Alp, additional, Alptekin, Köksal, additional, Saka, Meram C., additional, Arango, Celso, additional, O'Donovan, Michael, additional, Rutten, Bart P.F., additional, and Gülöksüz, Sinan, additional

Published
2020
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45. Do Current Measures of Polygenic Risk for Mental Disorders Contribute to Population Variance in Mental Health?

Author

Marsman, Anne, primary, Pries, Lotta-Katrin, additional, ten Have, Margreet, additional, de Graaf, Ron, additional, van Dorsselaer, Saskia, additional, Bak, Maarten, additional, Kenis, Gunter, additional, Lin, Bochao D, additional, Luykx, Jurjen J, additional, Rutten, Bart P F, additional, Guloksuz, Sinan, additional, and van Os, Jim, additional

Published
2020
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46. Association of preceding psychosis risk states and non‐psychotic mental disorders with incidence of clinical psychosis in the general population: a prospective study in the NEMESIS‐2 cohort

Author

Guloksuz, Sinan, primary, Pries, Lotta‐Katrin, additional, Have, Margreet, additional, Graaf, Ron, additional, Dorsselaer, Saskia, additional, Klingenberg, Boris, additional, Bak, Maarten, additional, Lin, Bochao D., additional, Eijk, Kristel R., additional, Delespaul, Philippe, additional, Amelsvoort, Therese, additional, Luykx, Jurjen J., additional, Rutten, Bart P.F., additional, and Os, Jim, additional

Published
2020
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48. A new genetic locus for antipsychotic-induced weight gain: A genome-wide study of first-episode psychosis patients using amisulpride (from the OPTiMiSE cohort)

Author

ter Hark, Sophie E, primary, Jamain, Stéphane, additional, Schijven, Dick, additional, Lin, Bochao D, additional, Bakker, Mark K, additional, Boland-Auge, Anne, additional, Deleuze, Jean-François, additional, Troudet, Réjane, additional, Malhotra, Anil K, additional, Gülöksüz, Sinan, additional, Vinkers, Christiaan H, additional, Ebdrup, Bjørn H, additional, Kahn, René S, additional, Leboyer, Marion, additional, and Luykx, Jurjen J, additional

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

Author

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

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

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

Published
2019

50. Assessing causal links between metabolic traits, inflammation and schizophrenia : a univariable and multivariable, bidirectional Mendelian-randomization study

Author

Lin, Bochao D., Alkema, Anne, Peters, Triinu, Zinkstok, Janneke, Libuda, Lars, Hebebrand, Johannes, Antel, Jochen, Hinney, Anke, Cahn, Wiepke, Adan, Roger, Luykx, Jurjen J., Lin, Bochao D., Alkema, Anne, Peters, Triinu, Zinkstok, Janneke, Libuda, Lars, Hebebrand, Johannes, Antel, Jochen, Hinney, Anke, Cahn, Wiepke, Adan, Roger, and Luykx, Jurjen J.

Published
2019

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