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1. The effect of polygenic risk score and childhood adversity on transdiagnostic symptom dimensions at first-episode psychosis: evidence for an affective pathway to psychosis

Author: Luis Alameda, Victoria Rodriguez, Marta Di Forti, Edoardo Spinazzola, Giulia Trotta, Celso Arango, Manuel Arrojo, Miguel Bernardo, Julio Bobes, Lieuwe de Haan, Cristina Marta Del-Ben, Charlotte Gayer-Anderson, Lucia Sideli, Peter B. Jones, James B. Kirkbride, Caterina La Cascia, Giada Tripoli, Laura Ferraro, Daniele La Barbera, Antonio Lasalvia, Sarah Tosato, Pierre-Michel Llorca, Paulo Rossi Menezes, Jim van Os, Bart P. Rutten, Jose Luis Santos, Julio Sanjuán, Jean-Paul Selten, Andrei Szöke, Ilaria Tarricone, Andrea Tortelli, Eva Velthorst, Hannah E. Jongsma, Evangelos Vassos, Diego Quattrone, Robin M. Murray, and Monica Aas
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Abstract Childhood adversity is associated with various clinical dimensions in psychosis; however, how genetic vulnerability shapes the adversity-associated psychopathological signature is yet to be studied. We studied data of 583 First Episode Psychosis (FEP) cases from the EU-GEI FEP case-control study, including Polygenic risk scores for major depressive disorder (MDD-PRS), bipolar disorder (BD-PRS) and schizophrenia (SZ-PRS); childhood adversity measured with the total score of the Childhood Trauma Questionnaire (CTQ); and positive, negative, depressive and manic psychopathological domains from a factor model of transdiagnostic dimensions. Genes and environment interactions were explored as a departure from a multiplicative effect of PRSs and total CTQ on each dimension. Analyses were adjusted for age, sex, 10 PCA, site of recruitment and for medication. A childhood adversity and PRS multiplicative interaction was observed between A) the CTQ and MDD-PRS on the predominance of positive (β = 0.42, 95% CI = [0.155, 0.682], p = 0.004); and depressive (β = 0.33, 95% CI = [0.071, 0.591], p = 0.013) dimensions; B) between the CTQ and BD-PRS on the positive dimension (β = 0.45, 95% CI = [0.106, 0.798], p = 0.010), and C) with the CTQ and SZ-PRS on the positive dimension (β = −0.34, 95% CI = [−0.660, −0.015], p = 0.040). Bonferroni corrected p-value of significance was set at 0.0125. In conclusion, despite being underpowered, this study suggests that genetic liability for MDD and BD may have a moderating effect on the sensibility of childhood adversity on depressive and positive psychotic dimensions. This supports the hypothesis of an affective pathway to psychosis in those exposed to childhood adversity.
Published: 2024
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2. Diminished social motivation in early psychosis is associated with polygenic liability for low vitamin D

Author: Alex Hatzimanolis, Sarah Tosato, Mirella Ruggeri, Doriana Cristofalo, Leonidas Mantonakis, Lida-Alkisti Xenaki, Stefanos Dimitrakopoulos, Mirjana Selakovic, Stefania Foteli, Ioannis Kosteletos, Ilias Vlachos, Rigas-Filippos Soldatos, Nikos Nianiakas, Irene Ralli, Konstantinos Kollias, Angeliki-Aikaterini Ntigrintaki, Pentagiotissa Stefanatou, Robin M. Murray, Evangelos Vassos, and Nikos C. Stefanis
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Abstract Insufficiency of vitamin D levels often occur in individuals with schizophrenia and first-episode psychosis (FEP). However, it is unknown whether this represents a biological predisposition, or it is essentially driven by illness-related alterations in lifestyle habits. Lower vitamin D has also been associated with adverse neurodevelopmental outcomes and predominant negative psychotic symptoms. This study aimed to investigate the contribution of polygenic risk score for circulating 25-hydroxyvitamin D concentration (PRS-vitD) to symptom presentation among individuals with FEP enrolled in the Athens First-Episode Psychosis Research Study (AthensFEP n = 205) and the Psychosis Incident Cohort Outcome Study (PICOS n = 123). The severity of psychopathology was evaluated using the Positive and Negative Syndrome Scale at baseline and follow-up assessments (AthensFEP: 4-weeks follow-up, PICOS: 1-year follow-up). Premorbid intelligence and adjustment domains were also examined as proxy measures of neurodevelopmental deviations. An inverse association between PRS-vitD and severity of negative symptoms, in particular lack of social motivation, was detected in the AthensFEP at baseline (adjusted R 2 = 0.04, p
Published: 2024
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3. Clinical and psychological characteristics associated with negative beliefs and concerns about treatment necessity in rheumatic diseases

Author: Sarah Tosato, Chiara Bonetto, Alice Zanini, Riccardo Bixio, Martina Marchel, Giulio Pacenza, Isotta Galvagni, Doriana Cristofalo, Elena Fracassi, and Antonio Carletto
Subjects: Medicine, Science
Abstract: Abstract Identifying factors that influence problematic beliefs and behaviors related to pharmacotherapy may be useful for clinicians to improve the patients’ adherence. The study aims to assess patients’ beliefs about the necessity and concerns regarding pharmacotherapy in rheumatic diseases and attitude styles, and to investigate the association between clinical factors and negative beliefs about medication. A sample of 712 patients affected by Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis was enrolled. They were assessed using the Beliefs about Medicines Questionnaires-Specific (BMQ), the Simplified Disease Activity Index (SDAI), the Visual Analogue Scale for pain (VAS), the Chalder Fatigue Scale (CFQ) and the Health Assessment Questionnaire-Disability Index (HAQ-DI). The balance between benefits and costs in the BMQ-Specific was positive in the 79.4% of patients, negative in the 12.1% and equal in the 8.6%. SDAI, taking more than 5 medications, taking anti interleukin 6 (Anti-IL6) or biological disease-modifying antirheumatic drugs (bDMARDs), or targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), pain, and fatigue were significantly associated to higher Concerns. Having a longer disease duration was significantly associated with a higher Necessity, together with the current pharmacological treatments and the disability. The multivariate regression models estimated that higher pain and fatigue were associated to higher Concerns (p
Published: 2022
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4. Using brain cell-type-specific protein interactomes to interpret neurodevelopmental genetic signals in schizophrenia

Author: Yu-Han H. Hsu, Greta Pintacuda, Ruize Liu, Eugeniu Nacu, April Kim, Kalliopi Tsafou, Natalie Petrossian, William Crotty, Jung Min Suh, Jackson Riseman, Jacqueline M. Martin, Julia C. Biagini, Daya Mena, Joshua K.T. Ching, Edyta Malolepsza, Taibo Li, Tarjinder Singh, Tian Ge, Shawn B. Egri, Benjamin Tanenbaum, Caroline R. Stanclift, Annie M. Apffel, Steven A. Carr, Monica Schenone, Jake Jaffe, Nadine Fornelos, Hailiang Huang, Kevin C. Eggan, Kasper Lage, Stephan Ripke, Benjamin M. Neale, Aiden Corvin, James T.R. Walters, Kai-How Farh, Peter A. Holmans, Phil Lee, Brendan Bulik-Sullivan, David A. Collier, Tune H. Pers, Ingrid Agartz, Esben Agerbo, Margot Albus, Madeline Alexander, Farooq Amin, Silviu A. Bacanu, Martin Begemann, Richard A. Belliveau, Jr., Judit Bene, Sarah E. Bergen, Elizabeth Bevilacqua, Tim B. Bigdeli, Donald W. Black, Richard Bruggeman, Nancy G. Buccola, Randy L. Buckner, William Byerley, Wiepke Cahn, Guiqing Cai, Dominique Campion, Rita M. Cantor, Vaughan J. Carr, Noa Carrera, Stanley V. Catts, Kimberley D. Chambert, Raymond C.K. Chan, Ronald Y.L. Chan, Eric Y.H. Chen, Wei Cheng, Eric FC. Cheung, Siow Ann Chong, C. Robert Cloninger, David Cohen, Nadine Cohen, Paul Cormican, Nick Craddock, James J. Crowley, David Curtis, Michael Davidson, Kenneth L. Davis, Franziska Degenhardt, Jurgen Del Favero, Ditte Demontis, Dimitris Dikeos, Timothy Dinan, Srdjan Djurovic, Gary Donohoe, Elodie Drapeau, Jubao Duan, Frank Dudbridge, Naser Durmishi, Peter Eichhammer, Johan Eriksson, Valentina Escott-Price, Laurent Essioux, Ayman H. Fanous, Martilias S. Farrell, Josef Frank, Lude Franke, Robert Freedman, Nelson B. Freimer, Marion Friedl, Joseph I. Friedman, Menachem Fromer, Giulio Genovese, Lyudmila Georgieva, Ina Giegling, Paola Giusti-Rodríguez, Stephanie Godard, Jacqueline I. Goldstein, Vera Golimbet, Srihari Gopal, Jacob Gratten, Lieuwe de Haan, Christian Hammer, Marian L. Hamshere, Mark Hansen, Thomas Hansen, Vahram Haroutunian, Annette M. Hartmann, Frans A. Henskens, Stefan Herms, Joel N. Hirschhorn, Per Hoffmann, Andrea Hofman, Mads V. Hollegaard, David M. Hougaard, Masashi Ikeda, Inge Joa, Antonio Julià, René S. Kahn, Luba Kalaydjieva, Sena Karachanak-Yankova, Juha Karjalainen, David Kavanagh, Matthew C. Keller, James L. Kennedy, Andrey Khrunin, Yunjung Kim, Janis Klovins, James A. Knowles, Bettina Konte, Vaidutis Kucinskas, Zita Ausrele Kucinskiene, Hana Kuzelova-Ptackova, Anna K. Kähler, Claudine Laurent, Jimmy Lee, S. Hong Lee, Sophie E. Legge, Bernard Lerer, Miaoxin Li, Tao Li, Kung-Yee Liang, Jeffrey Lieberman, Svetlana Limborska, Carmel M. Loughland, Jan Lubinski, Jouko Lönnqvist, Milan Macek, Patrik K.E. Magnusson, Brion S. Maher, Wolfgang Maier, Jacques Mallet, Sara Marsal, Manuel Mattheisen, Morten Mattingsdal, Robert W. McCarley, Colm McDonald, Andrew M. McIntosh, Sandra Meier, Carin J. Meijer, Bela Melegh, Ingrid Melle, Raquelle I. Mesholam-Gately, Andres Metspalu, Patricia T. Michie, Lili Milani, Vihra Milanova, Younes Mokrab, Derek W. Morris, Ole Mors, Kieran C. Murphy, Robin M. Murray, Inez Myin-Germeys, Bertram Müller-Myhsok, Mari Nelis, Igor Nenadic, Deborah A. Nertney, Gerald Nestadt, Kristin K. Nicodemus, Liene Nikitina-Zake, Laura Nisenbaum, Annelie Nordin, Eadbhard O'Callaghan, Colm O'Dushlaine, F. Anthony O'Neill, Sang-Yun Oh, Ann Olincy, Line Olsen, Jim Van Os, Christos Pantelis, George N. Papadimitriou, Sergi Papiol, Elena Parkhomenko, Michele T. Pato, Tiina Paunio, Milica Pejovic-Milovancevic, Diana O. Perkins, Olli Pietiläinen, Jonathan Pimm, Andrew J. Pocklington, John Powell, Alkes Price, Ann E. Pulver, Shaun M. Purcell, Digby Quested, Henrik B. Rasmussen, Abraham Reichenberg, Mark A. Reimers, Alexander L. Richards, Joshua L. Roffman, Panos Roussos, Douglas M. Ruderfer, Veikko Salomaa, Alan R. Sanders, Ulrich Schall, Christian R. Schubert, Thomas G. Schulze, Sibylle G. Schwab, Edward M. Scolnick, Rodney J. Scott, Larry J. Seidman, Jianxin Shi, Engilbert Sigurdsson, Teimuraz Silagadze, Jeremy M. Silverman, Kang Sim, Petr Slominsky, Jordan W. Smoller, Hon-Cheong So, Chris C.A. Spencer, Eli A. Stahl, Hreinn Stefansson, Stacy Steinberg, Elisabeth Stogmann, Richard E. Straub, Eric Strengman, Jana Strohmaier, T Scott Stroup, Mythily Subramaniam, Jaana Suvisaari, Dragan M. Svrakic, Jin P. Szatkiewicz, Erik Söderman, Srinivas Thirumalai, Draga Toncheva, Sarah Tosato, Juha Veijola, John Waddington, Dermot Walsh, Dai Wang, Qiang Wang, Bradley T. Webb, Mark Weiser, Dieter B. Wildenauer, Nigel M. Williams, Stephanie Williams, Stephanie H. Witt, Aaron R. Wolen, Emily H.M. Wong, Brandon K. Wormley, Hualin Simon Xi, Clement C. Zai, Xuebin Zheng, Fritz Zimprich, Naomi R. Wray, Kari Stefansson, Peter M. Visscher, Rolf Adolfsson, Ole A. Andreassen, Douglas H.R. Blackwood, Elvira Bramon, Joseph D. Buxbaum, Anders D. Børglum, Sven Cichon, Ariel Darvasi, Enrico Domenici, Hannelore Ehrenreich, Tõnu Esko, Pablo V. Gejman, Michael Gill, Hugh Gurling, Christina M. Hultman, Nakao Iwata, Assen V. Jablensky, Erik G. Jönsson, Kenneth S. Kendler, George Kirov, Jo Knight, Todd Lencz, Douglas F. Levinson, Qingqin S. Li, Jianjun Liu, Anil K. Malhotra, Steven A. McCarroll, Andrew McQuillin, Jennifer L. Moran, Preben B. Mortensen, Bryan J. Mowry, Markus M. Nöthen, Roel A. Ophoff, Michael J. Owen, Aarno Palotie, Carlos N. Pato, Tracey L. Petryshen, Danielle Posthuma, Marcella Rietschel, Brien P. Riley, Dan Rujescu, Pak C. Sham, Pamela Sklar, David St Clair, Daniel R. Weinberger, Jens R. Wendland, Thomas Werge, Mark J. Daly, Patrick F. Sullivan, Michael C. O'Donovan, Shengying Qin, Akira Sawa, Rene Kahn, Kyung Sue Hong, Wenzhao Shi, Ming Tsuang, Masanari Itokawa, Gang Feng, Stephen J. Glatt, Xiancang Ma, Jinsong Tang, Yunfeng Ruan, Feng Zhu, Yasue Horiuchi, Byung Dae Lee, Eun-Jeong Joo, Woojae Myung, Kyooseob Ha, Hong-Hee Won, Ji Hyung Baek, Young Chul Chung, Sung-Wan Kim, Agung Kusumawardhani, Wei J. Chen, Hai-Gwo Hwu, Akitoyo Hishimoto, Ikuo Otsuka, Ichiro Sora, Tomoko Toyota, Takeo Yoshikawa, Hiroshi Kunugi, Kotaro Hattori, Sayuri Ishiwata, Shusuke Numata, Tetsuro Ohmori, Makoto Arai, Yuji Ozeki, Kumiko Fujii, Se Joo Kim, Heon-Jeong Lee, Yong Min Ahn, Se Hyun Kim, Kazufumi Akiyama, Kazutaka Shimoda, and Makoto Kinoshita
Subjects: Molecular interaction, Developmental neuroscience, Cellular neuroscience, Proteomics, Science
Abstract: Summary: Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons. The resulting protein network is enriched for common variant risk of schizophrenia in Europeans and East Asians, is down-regulated in layer 5/6 cortical neurons of individuals affected by schizophrenia, and can complement fine-mapping and eQTL data to prioritize additional genes in GWAS loci. A sub-network centered on HCN1 is enriched for common variant risk and contains proteins (HCN4 and AKAP11) enriched for rare protein-truncating mutations in individuals with schizophrenia and bipolar disorder. Our findings showcase brain cell-type-specific interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in schizophrenia and its related disorders.
Published: 2023
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5. Post-migration trajectories and psychopathological vulnerability

Author: I. Tarricone, Ilaria Tarricone, Giuseppe D’Andrea, Hannah E Jongsma, Sarah Tosato, Charlotte Gayer-Anderson, Simona A. Stilo, Federico Suprani, Conrad Iyegbe, Els van der Ven, Diego Quattrone, Marta di Forti, Eva Velthorst, Paulo Rossi Menezes, Celso Arango, and Mara Parel
Subjects: Psychiatry, RC435-571
Abstract: Abstract: Background Psychosis rates are higher among some migrant groups. We hypothesized that psychosis in migrants is associated with cumulative social disadvantage during different phases of migration. Methods We used data from the EUropean Network of National Schizophrenia Networks studying Gene-Environment Interactions (EU-GEI) case-control study. We defined a set of 3 indicators of social disadvantage for each phase: pre-migration, migration, and post-migration. Results 249 cases and 219 controls were assessed. Pre-migration (OR 1.61, 95%CI 1.06-2.44, p=0.027) and postmigration social disadvantages (OR 1.89, 95%CI 1.02-3.51, p=0.044), along with expectations/achievements mismatch (OR 1.14, 95%CI 1.03-1.26, p=0.014) were all significantly associated with psychosis. We found a dose-response effect between number of adversities across all phases and odds of psychosis (≥6: OR 14.09, 95%CI 2.06-96-47, p=0.007). Conclusions The cumulative effect of social disadvantages before, during and after migration was associated with increased odds of psychosis in migrants, independently of ethnicity or length of stay in the country of arrival. Public health initiatives that address the social disadvantages that many migrants face during the whole migration process and post-migration psychological support may be reduce the excess of psychosis in migrants. Disclosure of Interest None Declared
Published: 2023
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6. Depression is associated with increased disease activity and higher disability in a large Italian cohort of patients with rheumatoid arthritis

Author: Sara Pezzato, Chiara Bonetto, Cristian Caimmi, Simona Tomassi, Ilaria Montanari, Maria Giulia Gnatta, Elena Fracassi, Doriana Cristofalo, Maurizio Rossini, Antonio Carletto, and Sarah Tosato
Subjects: Depression, Rheumatoid arthritis, Disease activity, Disability, Diseases of the musculoskeletal system, RC925-935, Immunologic diseases. Allergy, RC581-607
Abstract: Abstract Introduction Depression is a quite common comorbidity in patients with rheumatoid arthritis (RA) and is thought to influence its severity. This study aims to estimate, in a large cohort of Italian patients with RA, the prevalence of depression and to investigate the clinical correlates of depression in terms of disease activity and disability. Methods This is a cross-sectional study enrolling 490 outpatients with RA (80% female, mean age 59.5). The Hospital Anxiety and Depression Scale (HADS) was used to assess the presence of depression with a cut-off of 11. We collected data about disease activity and disability with DAS28, TJC-68, PhGA, PGA, VAS, DAS28, SDAI, CDAI and HAQ. Results Prevalence of depression was 14.3% (95% CI: 11-17%). Depressed patients, when compared with not depressed ones, were found to have higher scores for TJC-68 (p = 0.011), PhGA (p = 0.001), PGA (p = 0.001), VAS (p = 0.001), DAS28 (p = 0.007), SDAI (p = 0.001), CDAI (p = 0.001) and HAQ (p = 0.001). Out of the 70 depressed patients, 30 subjects, already known to be depressed in the past, were still depressed at the time of the assessment, with only 11 (15.7%) under antidepressants. A multivariate analysis showed that male sex, higher PGA score, use of antidepressants and higher HAQ score were significantly associated with an increased risk of depression. Conclusions Our study shows that depression is common in RA and may affect its activity mainly via an alteration in the perception of the disease. Although its important implications, depression is still under-diagnosed and its management is inadequate.
Published: 2021
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7. 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: Diego Quattrone, Ulrich Reininghaus, Alex L. Richards, Giada Tripoli, Laura Ferraro, Andrea Quattrone, Paolo Marino, Victoria Rodriguez, Edoardo Spinazzola, Charlotte Gayer-Anderson, Hannah E. Jongsma, Peter B. Jones, Caterina La Cascia, Daniele La Barbera, Ilaria Tarricone, Elena Bonora, Sarah Tosato, Antonio Lasalvia, Andrei Szöke, Celso Arango, Miquel Bernardo, Julio Bobes, Cristina Marta Del Ben, Paulo Rossi Menezes, Pierre-Michel Llorca, Jose Luis Santos, Julio Sanjuán, Manuel Arrojo, Andrea Tortelli, Eva Velthorst, Steven Berendsen, Lieuwe de Haan, Bart P. F. Rutten, Michael T. Lynskey, Tom P. Freeman, James B. Kirkbride, Pak C. Sham, Michael C. O’Donovan, Alastair G. Cardno, Evangelos Vassos, Jim van Os, Craig Morgan, Robin M. Murray, Cathryn M. Lewis, Marta Di Forti, and EU-GEI collaborators
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: 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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8. Childhood and Adulthood Severe Stressful Experiences and Biomarkers Related to Glucose Metabolism: A Possible Association?

Author: Sarah Tosato, Chiara Bonetto, Nicola Lopizzo, Nadia Cattane, Mara Barcella, Giorgia Turco, Mirella Ruggeri, Stefania Provasi, Simona Tomassi, Paola Dazzan, and Annamaria Cattaneo
Subjects: childhood trauma, glucose, health outcome, insulin, stressful life events, Psychiatry, RC435-571
Abstract: Background: No study investigated the association between stress exposure in different stages of life and metabolic dysfunction.Aim: We explore the association between stress exposure and several biomarkers related to glucose metabolism (insulin, c-peptide, GIP, GLP-1, glucagon) in a group of 72 healthy individuals.Method: We used the Childhood Experience of Care and Abuse-Questionnaire (CECA-Q) and a modified version of the Life Events Scale to define exposure to stress, according to four categories: no exposure to childhood trauma (CT) nor to stressful life events (SLEs) (46%), only to CT (25%), only to SLEs (21%), to both (8%).Results: We found that c-peptide (p = 0.006) and insulin (p = 0.002) levels differed among the four categories: 0.77 ng/ml (SD 0.27) and 0.21 ng/ml (SD 0.06) for none, 0.77 (SD 0.37) and 0.20 (SD 0.08) for only SLEs, 0.88 (SD 0.39) and 0.27 (SD 0.12) for only CT, 1.33 (SD 0.57) and 0.40 (SD 0.28) for both, respectively. The highest levels of biomarkers were found in subjects exposed to both CT and SLEs.Conclusion: Our preliminary results seem to suggest that CT might be specifically associated with a dysfunction of glucose metabolism, which might increase the risk of poorer health outcomes in adulthood. This association seems to be even stronger in individuals additionally exposed to SLEs in adulthood. In conclusion, if confirmed in other studies, subjects exposed to both CT and SLEs appear the most vulnerable individuals, for whom preventative interventions, such as healthy lifestyle education programs, might ameliorate the risk of developing metabolic abnormalities.
Published: 2021
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9. Cannabis and Cognition: Connecting the Dots towards the Understanding of the Relationship

Author: Marco Colizzi, Sarah Tosato, and Mirella Ruggeri
Subjects: delta-9-tetrahydrocannabinol, endocannabinoid system, executive functions, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Several studies have advanced the understanding of the effects of cannabis on cognitive function. A comprehensive reappraisal of such literature may help in drawing conclusions about the potential risks associated with cannabis use. In summary, the evidence suggests that earlier age of use, high-frequency and high-potency cannabis use, as well as sustained use over time and use of synthetic cannabinoids, are all correlated with a higher likelihood of developing potentially severe and persistent executive function impairments. While the exact mechanisms underlying the adverse effects of cannabis on cognition are not completely clear, Magnetic Resonance Imaging (MRI) studies support the presence of both structural and functional alterations associated with cannabis use. Cognitive dysfunction is also a core feature of many neuropsychiatric disorders and care must be taken regarding the effects of cannabis use in these patient populations. Cognitive impairments affect patients’ daily functions, sociability, and long-term outcome, posing elevated economic, social, and clinical burdens. There is, thus, a compelling case for implementing behavioral and cognitive rehabilitation therapies for these patients, as well as investigating the endocannabinoid system in the development of new psychopharmacological treatments.
Published: 2020
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10. Family Burden, Emotional Distress and Service Satisfaction in First Episode Psychosis. Data from the GET UP Trial

Author: Mirella Ruggeri, Antonio Lasalvia, Paolo Santonastaso, Francesca Pileggi, Emanuela Leuci, Maurizio Miceli, Silvio Scarone, Stefano Torresani, Sarah Tosato, Katia De Santi, Doriana Cristofalo, Carla Comacchio, Simona Tomassi, Carla Cremonese, Angelo Fioritti, Giovanni Patelli, Chiara Bonetto, and The GET UP Group
Subjects: early psychosis, relatives, outcomes, pragmatic trial, community psychiatry, Psychology, BF1-990
Abstract: Background: Literature has documented the role of family in the outcome of chronic schizophrenia. In the light of this, family interventions (FIs) are becoming an integral component of treatment for psychosis. The First Episode of Psychosis (FEP) is the period when most of the changes in family atmosphere are observed; unfortunately, few studies on the relatives are available.Objective: To explore burden of care and emotional distress at baseline and at 9-month follow-up and the levels of service satisfaction at follow-up in the two groups of relatives (experimental treatment EXP vs. treatment as usual TAU) recruited in the cluster-randomized controlled GET UP PIANO trial.Methods: The experimental treatment was provided by routine public Community Mental Health Centers (Italian National Health Service) and consisted of Treatment as Usual plus evidence-based additional treatment (Cognitive Behavioral Therapy for psychosis for patients, Family Intervention for psychosis, and Case Management). TAU consisted of personalized outpatient psychopharmacological treatment, combined with non-specific supportive clinical management and informal support/educational sessions for families. The outcomes on relatives were assessed by the Involvement Evaluation Questionnaire (IEQ-EU), the General Health Questionnaire (GHQ-12), and the Verona Service Satisfaction Scale (VSSS-EU). Differences within and between groups were evaluated.Results: At baseline, 75 TAU and 185 EXP caregivers were assessed. In the experimental group 92% of relatives participated in at least 1 family session. At follow-up both groups experienced improvement in all IEQ and GHQ items, but caregivers belonging to the EXP arm experienced a significantly greater change in 10 IEQ items (mainly pertaining to the “Tension” dimension) and in GHQ items. Due to the low sample size, a significant effectiveness was only observed for 2 IEQ items and 1 GHQ-12 item. With respect to VSSS data at follow-up, caregivers in the EXP arm experienced significantly greater satisfaction in 8 items, almost all pertaining to the dimensions “Relatives' Involvement” and “Professionals' Skills and Behavior.”Conclusions: The Family intervention for psychosis delivered in the GET UP PIANO trial reduced family burden of illness and improved emotional distress and satisfaction with services. These results should encourage to promote FIs on caregivers of first-episode psychosis patients.
Published: 2017
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11. Child maltreatment, migration and risk of first-episode psychosis: results from the multinational EU-GEI study

Author: Giuseppe D'Andrea, Jatin Lal, Sarah Tosato, Charlotte Gayer-Anderson, Hannah E. Jongsma, Simona A. Stilo, Els van der Ven, Diego Quattrone, Eva Velthorst, Domenico Berardi, Paulo Rossi Menezes, Celso Arango, Mara Parellada, Antonio Lasalvia, Caterina La Cascia, Laura Ferraro, Daniele La Barbera, Lucia Sideli, Julio Bobes, Miguel Bernardo, Julio Sanjuán, Jose Luis Santos, Manuel Arrojo, Cristina Marta Del-Ben, Giada Tripoli, Pierre-Michel Llorca, Lieuwe de Haan, Jean-Paul Selten, Andrea Tortelli, Andrei Szöke, Roberto Muratori, Bart P. Rutten, Jim van Os, Peter B. Jones, James B. Kirkbride, Robin M. Murray, Marta di Forti, Ilaria Tarricone, Craig Morgan, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, RS: MHeNs - R3 - Neuroscience, MUMC+: MA Psychiatrie (3), Clinical Developmental Psychology, and World Health Organization (WHO) Collaborating Center
Subjects: INVOLVEMENT, childhood trauma, migrants, Child adversity, HISTORIES, INCREASE, PREVALENCE, Psychiatry and Mental health, IMMIGRANT FAMILIES, DISPARITIES, ADVERSITIES, HEALTH, first-episode psychosis, ABUSE, Applied Psychology
Abstract: The EU-GEI Project was funded by grant agreement Health-F2-2010-241909 from the European Community’s Seventh Framework program. The Brazilian study was funded by grant 2012-0417-0 from the São Paulo Research Foundation, D'Andrea, Giuseppe; Lal, Jatin; Tosato, Sarah;Gayer-Anderson, Charlotte;Jongsma, Hannah E.;Stilo, Simona A.; van der Ven, Els;Quattrone, Diego;Velthorst, Eva;Berardi, Domenico;Rossi Menezes, Paulo; Arango, Celso; Parellada, Mara; Lasalvia, Antonio; La Cascia, Caterina; Ferraro, Laura; La Barbera, Daniele; Sideli, Lucia; Bobes, Julio; Bernardo, Miguel; Sanjuan, Julio; Santos, Jose Luis; Arrojo, Manuel; Marta Del-Ben, Cristina; Tripoli, Giada; Llorca, Pierre-Michel; de Haan, Lieuwe; Selten, Jean-Paul; Tortelli, Andrea; Szoke, Andrei; Muratori, Roberto; Rutten, Bart P.; van Os, Jim; Jones, Peter B.; Kirkbride, James B.; Murray, Robin M.; di Forti, Marta; Tarricone, Ilaria; Morgan, Craig
Published: 2022
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12. Classification of first-episode psychosis in a large cohort of patients using support vector machine and multiple kernel learning techniques.

Author: Letizia Squarcina, Umberto Castellani, Marcella Bellani, Cinzia Perlini, Antonio Lasalvia, Nicola Dusi, Chiara Bonetto, Doriana Cristofalo, Sarah Tosato, Gianluca Rambaldelli, Franco Alessandrini, Giada Zoccatelli, Roberto Pozzi Mucelli, Dario Lamonaca, Enrico Ceccato, Francesca Pileggi, Fausto Mazzi, Paolo Santonastaso, Mirella Ruggeri, and Paolo Brambilla
Published: 2017
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13. Exploring the mediation of DNA methylation across the epigenome between childhood adversity and First Episode of Psychosis-findings from the EU-GEI study

Author: Luis Alameda, Zhonghua Liu, Pak C. Sham, Monica Aas, Giulia Trotta, Victoria Rodriguez, Marta Di Forti, Simona A. Stilo, Radhika Kandaswamy, Celso Arango, Manuel Arrojo, Miguel Bernardo, Julio Bobes, Lieuwe de Haan, Cristina Marta Del-Ben, Charlotte Gayer-Anderson, Lucia Sideli, Peter B. Jones, Hannah E. Jongsma, James B. Kirkbride, Caterina La Cascia, Antonio Lasalvia, Sarah Tosato, Pierre-Michel Llorca, Paulo Rossi Menezes, Jim van Os, Diego Quattrone, Bart P. Rutten, Jose Luis Santos, Julio Sanjuán, Jean-Paul Selten, Andrei Szöke, Ilaria Tarricone, Andrea Tortelli, Eva Velthorst, Craig Morgan, Emma Dempster, Eilis Hannon, Joe Burrage, Daniella Dwir, Atheeshaan Arumuham, Jonathan Mill, Robin M. Murray, and Chloe C. Y. Wong
Subjects: BLOOD, FAMOTIDINE, NIZATIDINE, predictive markers, ASSOCIATION, WEIGHT-GAIN, Cellular and Molecular Neuroscience, Psychiatry and Mental health, psychotic disorders, childhood adversity, SCHIZOPHRENIA, RELIABILITY, genetics, OLANZAPINE, Molecular Biology, HISTAMINE H-2-RECEPTOR, GENE-EXPRESSION
Abstract: AbtractStudies conducted in psychotic disorders have shown that DNA-methylation (DNAm) is sensitive to the impact of Childhood Adversity (CA). However, whether it mediates the association between CA and psychosis is yet to be explored. Epigenome wide association studies (EWAS) using the Illumina Infinium-Methylation EPIC array in peripheral blood tissue from 366 First-episode of psychosis and 517 healthy controls was performed. Adversity scores were created for abuse, neglect and composite adversity with the Childhood Trauma Questionnaire (CTQ). Regressions examining (I) CTQ scores with psychosis; (II) with DNAm EWAS level and (III) between DNAm and caseness, adjusted for a variety of confounders were conducted. Divide-Aggregate Composite-null Test for the composite null-hypothesis of no mediation effect was conducted. Enrichment analyses were conducted with missMethyl package and the KEGG database. Our results show that CA was associated with psychosis (Composite: OR = 1.68; p = p < 0.001; neglect: OR = 2.27; p =
Published: 2023
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14. Exploring the mediation of DNA methylation across the epigenome between childhood adversity and First Episode of Psychosis – findings from the EU-GEI study

Author: Luis Alameda, Zhonghua Liu, Pak Sham, AAS Monica, Trotta Giulia, Rodriguez Victoria, Marta di Forti, Stilo Simona, Kandaswamy Radhika, Celso Arango, Manuel Arrojo, Miquel Bernardo, Julio Bobes, Lieuwe de Haan, Cristina Del-Ben, Charlotte Gayer-Anderson, Sideli Lucia, Peter Jones, Hannah Jongsma, James Kirkbride, Caterina La Cascia, Antonio Lasalvia, Sarah Tosato, Pierre Michel Llorca, Paulo Menezes, Jim van Os, Quattrone Diego, Bart Rutten, José Santos, Julio Sanjuan, Jean-Paul Selten, Andrei Szöke, Ilaria Tarricone, Andrea Tortelli, Eva Velthorst, Craig Morgan, Emma Dempster, Eilis Hannon, Joe Burrage, Jonathan Mill, Robin Murray, and Chloe Wong
Abstract: Studies conducted in psychotic disorders have shown that DNA-methylation (DNAm) is sensitive to the impact of Childhood Adversity (CA). However, whether it mediates the association between CA and psychosis is yet to be explored. Epigenome-wide association studies (EWAS) using the Illumina Infinium-Methylation EPIC array in peripheral blood tissue from 366 First-episode of psychosis and 517 healthy controls was performed. Polyvictimization scores were created for abuse, neglect, and composite adversity with the Childhood Trauma Questionnaire (CTQ). Regressions examining (I) CTQ scores with psychosis; (II) with DNAm EWAS level and (III), then between DNAm and caseness, adjusted for a variety of confounders were conducted. Divide-Aggregate Composite-null Test for the composite null hypothesis of no mediation effect was conducted. Enrichment analyses were conducted with missMethyl package and the KEGG database. Our results show that CA was associated with psychosis (Composite: OR = 3.09; p =
Published: 2022
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15. Jumping to conclusions, general intelligence, and psychosis liability: Findings from the multi-centre EU-GEI case-control study

Author: Fabio Seminerio, Andrei Szöke, Antonio Lasalvia, Diego Quattrone, Domenico Berardi, Jean-Paul Selten, Ilaria Tarricone, Peter B. Jones, Graham K. Murray, Miguel Bernardo, José Luis Santos, Pierre-Michel Llorca, Alexander Richards, Caterina La Cascia, Celso Arango, Manuel Arrojo, Victoria Rodriguez, Lieuwe de Haan, Craig Morgan, Crocettarachele Sartorio, Michael Conlon O'Donovan, Andrea Tortelli, Laura Ferraro, Julio Sanjuán, Robin M. Murray, Hannah E. Jongsma, Marta Di Forti, Cristina Marta Del-Ben, Eva Velthorst, Jim van Os, Daniele La Barbera, Bart P. F. Rutten, Julio Bobes, Sarah Tosato, Pak C. Sham, James B. Kirkbride, Paulo Rossi Menezes, Charlotte Gayer-Anderson, Giada Tripoli, Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Tripoli G., Quattrone D., Ferraro L., Gayer-Anderson C., Rodriguez V., La Cascia C., La Barbera D., Sartorio C., Seminerio F., Tarricone I., Berardi D., Szoke A., Arango C., Tortelli A., Llorca P.-M., De Haan L., Velthorst E., Bobes J., Bernardo M., Sanjuan J., Santos J.L., Arrojo M., Del-Ben C.M., Menezes P.R., Selten J.-P., Jones P.B., Jongsma H.E., Kirkbride J.B., Lasalvia A., Tosato S., Richards A., O'donovan M., Rutten B.P.F., Os J.V., Morgan C., Sham P.C., Murray R.M., Murray G.K., Di Forti M., Adult Psychiatry, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, Tripoli, Giada, Quattrone, Diego, Ferraro, Laura, Gayer-Anderson, Charlotte, Rodriguez, Victoria, La Cascia, Caterina, La Barbera, Daniele, Sartorio, Crocettarachele, Seminerio, Fabio, Tarricone, Ilaria, Berardi, Domenico, Szöke, Andrei, Arango, Celso, Tortelli, Andrea, Llorca, Pierre-Michel, de Haan, Lieuwe, Velthorst, Eva, Bobes, Julio, Bernardo, Miguel, Sanjuán, Julio, Santos, Jose Lui, Arrojo, Manuel, Del-Ben, Cristina Marta, Menezes, Paulo Rossi, Selten, Jean-Paul, Jones, Peter B, Jongsma, Hannah E, Kirkbride, James B, Lasalvia, Antonio, Tosato, Sarah, Richards, Alex, O'Donovan, Michael, Rutten, Bart Pf, Os, Jim van, Morgan, Craig, Sham, Pak C, Murray, Robin M, Murray, Graham K, Di Forti, Marta, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, MUMC+: MA Psychiatrie (3), and MUMC+: Hersen en Zenuw Centrum (3)
Subjects: Male, MISCOMPREHENSION, Intelligence, DELÍRIO, 0302 clinical medicine, Cognition, SCHIZOPHRENIA, psychotic-like experience, jumping to conclusions, Applied Psychology, Problem Solving, RISK, education.field_of_study, Middle Aged, 16. Peace & justice, Cognitive bias, 3. Good health, First episode psychosis, IQ, polygenic risk score, psychotic-like experiences, symptom dimensions, Psychiatry and Mental health, BIAS, Schizophrenia, RELIABILITY, Female, Original Article, jumping to conclusion, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Clinical psychology, Adult, Psychosis, Adolescent, DISORDERS, Population, REEXAMINATION, Delusions, 03 medical and health sciences, Young Adult, PEOPLE, medicine, Humans, Cognitive Dysfunction, education, DELUSIONAL IDEATION, Cognitive deficit, business.industry, Case-control study, medicine.disease, First episode psychosi, 030227 psychiatry, Psychotic Disorders, Case-Control Studies, Jumping to conclusions, business, 030217 neurology & neurosurgery
Abstract: This study was funded by the Medical Research Council, the European Community’s Seventh Framework Program grant [agreement HEALTH-F2-2009-241909 (Project EU-GEI)], São Paulo Research Foundation (grant 2012/0417-0), the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King’s College London, the NIHR BRC at University College London and the Wellcome Trust (grant 101272/Z/12/Z)., Tripoli, G., Quattrone, D., Ferraro, L., Gayer-Anderson, C., Rodriguez, V., La Cascia, C., La Barbera, D., Sartorio, C., Seminerio, F., Tarricone, I., Berardi, D., Szöke, A., Arango, C., Tortelli, A., Llorca, P.-M., De Haan, L., Velthorst, E., Bobes, J., Bernardo, M., Sanjuán, J., Santos, J.L., Arrojo, M., Del-Ben, C.M., Menezes, P.R., Selten, J.-P., Jones, P.B., Jongsma, H.E., Kirkbride, J.B., Lasalvia, A., Tosato, S., Richards, A., O'donovan, M., Rutten, B.P.F., Os, J.V., Morgan, C., Sham, P.C., Murray, R.M., Murray, G.K., Di Forti, M.
Published: 2021
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16. The incidence of psychotic disorders among migrants and minority ethnic groups in Europe: findings from the multinational EU-GEI study

Author: Lieuwe de Haan, Jim van Os, Bart P. F. Rutten, Sarah Tosato, Caterina La Cascia, Craig Morgan, Andrei Szöke, Ilaria Tarricone, Antonio Lasalvia, Diego Quattrone, Els van der Ven, Miguel Bernardo, James B. Kirkbride, Peter B. Jones, Eva Velthorst, Julio Sanjuán, Manuel Arrojo, Domenico Berardi, Charlotte Gayer-Anderson, Jean-Paul Selten, Fabian Termorshuizen, Pierre-Michel Llorca, Robin M. Murray, Hannah E Jongsma, Clinical Developmental Psychology, APH - Mental Health, World Health Organization (WHO) Collaborating Center, Termorshuizen F., Van Der Ven E., Tarricone I., Jongsma H.E., Gayer-Anderson C., Lasalvia A., Tosato S., Quattrone D., La Cascia C., Szoke A., Berardi D., Llorca P.-M., De Haan L., Velthorst E., Bernardo M., Sanjuan J., Arrojo M., Murray R.M., Rutten B.P., Jones P.B., Van Os J., Kirkbride J.B., Morgan C., Selten J.-P., Adult Psychiatry, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience, and MUMC+: MA Psychiatrie (3)
Subjects: medicine.medical_specialty, Dopamine, Region of origin, Ethnic group, migration, psychosi, stress, 03 medical and health sciences, Race (biology), 0302 clinical medicine, Epidemiology, medicine, Humans, psychosis, 10. No inequality, race, Minority Groups, Applied Psychology, Transients and Migrants, High rate, Incidence, Incidence (epidemiology), Social environment, PREVALENCE, 030227 psychiatry, 3. Good health, Europe, schizophrenia, Psychiatry and Mental health, Geography, Psychotic Disorders, Multinational corporation, 1ST-CONTACT INCIDENCE, ethnicity, epidemiology, 030217 neurology & neurosurgery, SOCIAL DEFEAT HYPOTHESIS, Demography
Abstract: BackgroundIn Europe, the incidence of psychotic disorder is high in certain migrant and minority ethnic groups (hence: ‘minorities’). However, it is unknown how the incidence pattern for these groups varies within this continent. Our objective was to compare, across sites in France, Italy, Spain, the UK and the Netherlands, the incidence rates for minorities and the incidence rate ratios (IRRs, minorities v. the local reference population).MethodsThe European Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI) study was conducted between 2010 and 2015. We analyzed data on incident cases of non-organic psychosis (International Classification of Diseases, 10th edition, codes F20–F33) from 13 sites.ResultsThe standardized incidence rates for minorities, combined into one category, varied from 12.2 in Valencia to 82.5 per 100 000 in Paris. These rates were generally high at sites with high rates for the reference population, and low at sites with low rates for the reference population. IRRs for minorities (combined into one category) varied from 0.70 (95% CI 0.32–1.53) in Valencia to 2.47 (95% CI 1.66–3.69) in Paris (test for interaction: p = 0.031). At most sites, IRRs were higher for persons from non-Western countries than for those from Western countries, with the highest IRRs for individuals from sub-Saharan Africa (adjusted IRR = 3.23, 95% CI 2.66–3.93).ConclusionsIncidence rates vary by region of origin, region of destination and their combination. This suggests that they are strongly influenced by the social context.
Published: 2020
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17. Neurological Signs at the First Psychotic Episode as Correlates of Long-Term Outcome: Results From the AESOP-10 Study

Author: Margaret Heslin, Craig Morgan, Robin M. Murray, Gillian A. Doody, Kim Donoghue, Naika P Ferruccio, Ben Lomas, Sarah Tosato, Raymond C.K. Chan, Adanna Onyejiaka, Paola Dazzan, Ulrich Reininghaus, Peter B. Jones, Paul Fearon, Tim Croudace, Julia Lappin, and Annalisa Giordano
Subjects: Neurological signs, Adult, Male, Pediatrics, medicine.medical_specialty, Psychosis, Adolescent, AcademicSubjects/MED00810, Population, clinical outcome, Perceptual Disorders, Young Adult, remission, Outcome Assessment, Health Care, medicine, Humans, first-episode psychosis, education, First episode, education.field_of_study, Dyskinesias, business.industry, Remission Induction, Middle Aged, medicine.disease, Health Surveys, United Kingdom, Motor coordination, Psychiatry and Mental health, Psychotic Disorders, Schizophrenia, Cohort, Etiology, Disease Progression, Female, neurological signs, Nervous System Diseases, business, Psychomotor Performance, Follow-Up Studies, Regular Articles
Abstract: Minor neurological signs are subtle deficits in sensory integration, motor coordination, and sequencing of complex motor acts present in excess in the early stages of psychosis. Still, it remains unclear whether at least some of these signs represent trait or state markers for psychosis and whether they are markers of long-term disease outcome of clinical utility. We examined the relationship between neurological function at illness onset assessed with the Neurological Evaluation Scale and subsequent illness course in 233 patients from AESOP-10 (Aetiology and Ethnicity in Schizophrenia and Other Psychoses), a 10-year follow-up study of a population-based cohort of individuals recruited at the time of their first episode of psychosis in the United Kingdom. In 56 of these patients, we also explored changes in neurological function over time. We included a group of 172 individuals without psychosis as controls. After 10 years, 147 (63%) patients had developed a non-remitting course of illness, and 86 (37%) a remitting course. Already at first presentation, patients who developed a non-remitting course had significantly more primary, motor coordination, and total signs than both remitting patients and healthy controls. While Motor Coordination signs did not change over time, rates of Primary, Sensory Integration, and Total signs increased, independently of illness course type. These findings suggest that motor coordination problems could be a useful early, quick, and easily detectable marker of subsequent clinical outcome. With other motor abnormalities, a measure of motor incoordination could contribute to the identification of the most vulnerable individuals, who could benefit from targeted and more assertive treatment approaches.
Published: 2020

18. Coping strategies, emotional distress and perceived disease severity in a cohort of patients with rheumatoid arthritis: a mediation analysis

Author: Sarah Tosato, Chiara Bonetto, Alice Zanini, Ilaria Montanari, Anna Piccinelli, Riccardo Bixio, Maurizio Rossini, Giulio Pacenza, Doriana Cristofalo, Elena Fracassi, and Antonio Carletto
Subjects: HADS, Rheumatology, PGA, Pharmacology (medical), Coping, Disease Severity, Rheumatoid arthritis, Emotional distress
Abstract: Objectives Few data are available on the role of emotional distress as a possible mediator of the relationship between coping strategies and the Patient Global Assessment (PGA). This study aims to investigate, in a large cohort of patients affected by RA, the relationship between specific copying strategies and PGA, and the role of emotional distress as a mediator. Methods A total of 490 patients with RA completed a set of standardized assessments including the self-reported PGA, the Coping Orientation to the Problems Experienced (COPE-NVI) and the Hospital Anxiety and Depression Scale (HADS). A mediation analysis was conducted to investigate the role of emotional distress. Results The effect of coping strategies on the PGA score was significantly mediated by the emotional distress for religious (total effect mediated 42.0%), planning (total effect mediated 17.5%), behavioural disengagement (total effect mediated 10.5%), and focus on and venting of emotions (total effect mediated 9.8%). Seven coping strategies (acceptance, positive reinterpretation and growth, active coping, denial, humour, substance use-mental disengagement) resulted directly associated to PGA total score, but no mediation effect was found. The remaining four coping strategies were not associated to the PGA score. Conclusion This study suggests that coping strategies could be an important factor in the perceived disease severity. Consequently, in order to reduce PGA in patients with RA, a useful tool could be represented by the implementation of psychological interventions aiming to modify the specific coping styles. Moreover, to prevent or treat emotional distress seems to further reduce PGA.
Published: 2022

19. Three-Month Follow-up Study of Mental Health Outcomes After a National COVID-19 Lockdown

Author: Claudia Carmassi, Liliana Dell’Osso, Carlo Antonio Bertelloni, Virginia Pedrinelli, Valerio Dell’Oste, Annalisa Cordone, Mirella Ruggeri, Simone Schimmenti, Chiara Bonetto, and Sarah Tosato
Subjects: Male, Depression, Mood Disorders, SARS-CoV-2, Incidence, COVID-19, Anxiety, Middle Aged, Diagnostic and Statistical Manual of Mental Disorders, Stress Disorders, Post-Traumatic, Psychiatry and Mental health, Cost of Illness, Italy, Communicable Disease Control, Mental Health Recovery, Outcome Assessment, Health Care, Humans, Female, Follow-Up Studies
Published: 2022
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20. Use of multiple polygenic risk scores for distinguishing schizophrenia-spectrum disorder and affective psychosis categories in a first-episode sample; the EU-GEI study

Author: Victoria Rodriguez, Luis Alameda, Diego Quattrone, Giada Tripoli, Charlotte Gayer-Anderson, Edoardo Spinazzola, Giulia Trotta, Hannah E. Jongsma, Simona Stilo, Caterina La Cascia, Laura Ferraro, Daniele La Barbera, Antonio Lasalvia, Sarah Tosato, Ilaria Tarricone, Elena Bonora, Stéphane Jamain, Jean-Paul Selten, Eva Velthorst, Lieuwe de Haan, Pierre-Michel Llorca, Manuel Arrojo, Julio Bobes, Miguel Bernardo, Celso Arango, James Kirkbride, Peter B. Jones, Bart P. Rutten, Alexander Richards, Pak C. Sham, Michael O'Donovan, Jim Van Os, Craig Morgan, Marta Di Forti, Robin M. Murray, Evangelos Vassos, Adult Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Rodriguez, V, Alameda, L, Quattrone, D, Tripoli, G, Gayer-Anderson, C, Spinazzola, E, Trotta, G, Jongsma, HE, Stilo, S, La Cascia, C, Ferraro, L, La Barbera, D, Lasalvia, A, Tosato, S, Tarricone, I, Bonora, E, Jamain, S, Selten, JP, Velthorst, E, de Haan, L, Llorca, PM, Arrojo, M, Bobes, J, Bernardo, M, Arango, C, Kirkbride, J, Jones, PB, Rutten, BP, Richards, A, Sham, PC, O'Donovan, M, Van Os, J, Morgan, C, Di Forti, M, Murray, RM, Vassos, E, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, RS: MHeNs - R3 - Neuroscience, and MUMC+: MA Psychiatrie (3)
Subjects: bipolar disorder, Affective psychosis, diagnosis, GENETIC-RELATIONSHIPS, schizophrenia-spectrum disorder, Psychiatry and Mental health, Affective psychosis, bipolar disorder, diagnosis, genetics, polygenic score, psychosis, psychotic depression, schizophrenia-spectrum disorder, LIABILITY, psychotic depression, genetics, polygenic score, psychosis, GENOME-WIDE ASSOCIATION, Applied Psychology
Abstract: This work was supported by funding from the European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-2010-241909 (Project EU-GEI). (...) CA was supported by the Spanish Ministry of Science and Innovation; Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/024), co-financed by ERDF Funds from the European Commission, ‘A way of making Europe’, CIBERSAM. Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), Fundación Familia Alonso and Fundación Alicia Koplowitz. MB was supported by the Ministry of Economy and Competitivity (PI08/0208; PI11/00325; PI14/00612), Instituto de Salud Carlos III – ERDF Funds from the European Commission, ‘A way of making Europe’, CIBERSAM, by the CERCA Programme/Generalitat de Catalunya and Secretaria d’Universitats i Recerca del Departament d’Economia I Coneixement (2017SGR1355). Departament de Salut de la Generalitat de Catalunya, en la convocatoria corresponent a l’any 2017 de concessió de subvencions del PERIS 2016-2020, modalitat Projectes de recerca orientats a l’atenció primària, amb el codi d’expedient SLT006/17/00345; and grateful for the support of the Institut de Neurociències, Universitat de Barcelona., Rodriguez V., Alameda L., Quattrone D., Tripoli G., Gayer-Anderson C., Spinazzola E., Trotta G., Jongsma H.E., Stilo S., La Cascia C., Ferraro L., La Barbera D., Lasalvia A., Tosato S., Tarricone I., Bonora E., Jamain S., Selten J.-P., Velthorst E., De Haan L., Llorca P.-M., Arrojo M., Bobes J., Bernardo M., Arango C., Kirkbride J., Jones P.B., Rutten B.P., Richards A., Sham P.C., O'Donovan M., Van Os J., Morgan C., Di Forti M., Murray R.M., Vassos E.
Published: 2022
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21. Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders

Author: Gabriëlla A.M. Blokland, Jakob Grove, Chia-Yen Chen, Chris Cotsapas, Stuart Tobet, Robert Handa, David St Clair, Todd Lencz, Bryan J. Mowry, Sathish Periyasamy, Murray J. Cairns, Paul A. Tooney, Jing Qin Wu, Brian Kelly, George Kirov, Patrick F. Sullivan, Aiden Corvin, Brien P. Riley, Tõnu Esko, Lili Milani, Erik G. Jönsson, Aarno Palotie, Hannelore Ehrenreich, Martin Begemann, Agnes Steixner-Kumar, Pak C. Sham, Nakao Iwata, Daniel R. Weinberger, Pablo V. Gejman, Alan R. Sanders, Joseph D. Buxbaum, Dan Rujescu, Ina Giegling, Bettina Konte, Annette M. Hartmann, Elvira Bramon, Robin M. Murray, Michele T. Pato, Jimmy Lee, Ingrid Melle, Espen Molden, Roel A. Ophoff, Andrew McQuillin, Nicholas J. Bass, Rolf Adolfsson, Anil K. Malhotra, Nicholas G. Martin, Janice M. Fullerton, Philip B. Mitchell, Peter R. Schofield, Andreas J. Forstner, Franziska Degenhardt, Sabrina Schaupp, Ashley L. Comes, Manolis Kogevinas, José Guzman-Parra, Andreas Reif, Fabian Streit, Lea Sirignano, Sven Cichon, Maria Grigoroiu-Serbanescu, Joanna Hauser, Jolanta Lissowska, Fermin Mayoral, Bertram Müller-Myhsok, Beata Świątkowska, Thomas G. Schulze, Markus M. Nöthen, Marcella Rietschel, John Kelsoe, Marion Leboyer, Stéphane Jamain, Bruno Etain, Frank Bellivier, John B. Vincent, Martin Alda, Claire O’Donovan, Pablo Cervantes, Joanna M. Biernacka, Mark Frye, Susan L. McElroy, Laura J. Scott, Eli A. Stahl, Mikael Landén, Marian L. Hamshere, Olav B. Smeland, Srdjan Djurovic, Arne E. Vaaler, Ole A. Andreassen, Bernhard T. Baune, Tracy Air, Martin Preisig, Rudolf Uher, Douglas F. Levinson, Myrna M. Weissman, James B. Potash, Jianxin Shi, James A. Knowles, Roy H. Perlis, Susanne Lucae, Dorret I. Boomsma, Brenda W.J.H. Penninx, Jouke-Jan Hottenga, Eco J.C. de Geus, Gonneke Willemsen, Yuri Milaneschi, Henning Tiemeier, Hans J. Grabe, Alexander Teumer, Sandra Van der Auwera, Uwe Völker, Steven P. Hamilton, Patrik K.E. Magnusson, Alexander Viktorin, Divya Mehta, Niamh Mullins, Mark J. Adams, Gerome Breen, Andrew M. McIntosh, Cathryn M. Lewis, David M. Hougaard, Merete Nordentoft, Ole Mors, Preben B. Mortensen, Thomas Werge, Thomas D. Als, Anders D. Børglum, Tracey L. Petryshen, Jordan W. Smoller, Jill M. Goldstein, Stephan Ripke, Benjamin M. Neale, James T.R. Walters, Kai-How Farh, Peter A. Holmans, Phil Lee, Brendan Bulik-Sullivan, David A. Collier, Hailiang Huang, Tune H. Pers, Ingrid Agartz, Esben Agerbo, Margot Albus, Madeline Alexander, Farooq Amin, Silviu A. Bacanu, Richard A. Belliveau, Judit Bene, Sarah E. Bergen, Elizabeth Bevilacqua, Tim B. Bigdeli, Donald W. Black, Richard Bruggeman, Nancy G. Buccola, Randy L. Buckner, William Byerley, Wiepke Cahn, Guiqing Cai, Dominique Campion, Rita M. Cantor, Vaughan J. Carr, Noa Carrera, Stanley V. Catts, Kimberly D. Chambert, Raymond C.K. Chan, Ronald Y.L. Chen, Eric Y.H. Chen, Wei Cheng, Eric F.C. Cheung, Siow Ann Chong, C. Robert Cloninger, David Cohen, Nadine Cohen, Paul Cormican, Nick Craddock, James J. Crowley, David Curtis, Michael Davidson, Kenneth L. Davis, Jurgen Del Favero, Ditte Demontis, Dimitris Dikeos, Timothy Dinan, Gary Donohoe, Elodie Drapeau, Jubao Duan, Frank Dudbridge, Naser Durmishi, Peter Eichhammer, Johan Eriksson, Valentina Escott-Price, Laurent Essioux, Ayman H. Fanous, Martilias S. Farrell, Josef Frank, Lude Franke, Robert Freedman, Nelson B. Freimer, Marion Friedl, Joseph I. Friedman, Menachem Fromer, Giulio Genovese, Lyudmila Georgieva, Paola Giusti-Rodríguez, Stephanie Godard, Jacqueline I. Goldstein, Vera Golimbet, Srihari Gopal, Jacob Gratten, Lieuwe de Haan, Christian Hammer, Mark Hansen, Thomas Hansen, Vahram Haroutunian, Frans A. Henskens, Stefan Herms, Joel N. Hirschhorn, Per Hoffmann, Andrea Hofman, Mads V. Hollegaard, Masashi Ikeda, Inge Joa, Antonio Julià, René S. Kahn, Luba Kalaydjieva, Sena Karachanak-Yankova, Juha Karjalainen, David Kavanagh, Matthew C. Keller, James L. Kennedy, Andrey Khrunin, Yunjung Kim, Janis Klovins, Vaidutis Kucinskas, Zita Ausrele Kucinskiene, Hana Kuzelova-Ptackova, Anna K. Kähler, Claudine Laurent, Jimmy Lee Chee Keong, S. Hong Lee, Sophie E. Legge, Bernard Lerer, Miaoxin Li, Tao Li, Kung-Yee Liang, Jeffrey Lieberman, Svetlana Limborska, Carmel M. Loughland, Jan Lubinski, Jouko Lönnqvist, Milan Macek, Brion S. Maher, Wolfgang Maier, Jacques Mallet, Sara Marsal, Manuel Mattheisen, Morten Mattingsdal, Robert W. McCarley, Colm McDonald, Sandra Meier, Carin J. Meijer, Bela Melegh, Raquelle I. Mesholam-Gately, Andres Metspalu, Patricia T. Michie, Vihra Milanova, Younes Mokrab, Derek W. Morris, Kieran C. Murphy, Inez Myin-Germeys, Mari Nelis, Igor Nenadic, Deborah A. Nertney, Gerald Nestadt, Kristin K. Nicodemus, Liene Nikitina-Zake, Laura Nisenbaum, Annelie Nordin, Eadbhard O’Callaghan, Colm O’Dushlaine, F. Anthony O’Neill, Sang-Yun Oh, Ann Olincy, Line Olsen, Jim Van Os, Christos Pantelis, George N. Papadimitriou, Sergi Papiol, Elena Parkhomenko, Tiina Paunio, Milica Pejovic-Milovancevic, Diana O. Perkins, Olli Pietiläinen, Jonathan Pimm, Andrew J. Pocklington, John Powell, Alkes Price, Ann E. Pulver, Shaun M. Purcell, Digby Quested, Henrik B. Rasmussen, Abraham Reichenberg, Mark A. Reimers, Alexander L. Richards, Joshua L. Roffman, Panos Roussos, Douglas M. Ruderfer, Veikko Salomaa, Ulrich Schall, Christian R. Schubert, Sibylle G. Schwab, Edward M. Scolnick, Rodney J. Scott, Larry J. Seidman, Engilbert Sigurdsson, Teimuraz Silagadze, Jeremy M. Silverman, Kang Sim, Petr Slominsky, Hon-Cheong So, Chris C.A. Spencer, Hreinn Stefansson, Stacy Steinberg, Elisabeth Stogmann, Richard E. Straub, Eric Strengman, Jana Strohmaier, T. Scott Stroup, Mythily Subramaniam, Jaana Suvisaari, Dragan M. Svrakic, Jin P. Szatkiewicz, Erik Söderman, Srinivas Thirumalai, Draga Toncheva, Sarah Tosato, Juha Veijola, John Waddington, Dermot Walsh, Dai Wang, Qiang Wang, Bradley T. Webb, Mark Weiser, Dieter B. Wildenauer, Nigel M. Williams, Stephanie Williams, Stephanie H. Witt, Aaron R. Wolen, Emily H.M. Wong, Brandon K. Wormley, Hualin Simon Xi, Clement C. Zai, Xuebin Zheng, Fritz Zimprich, Naomi R. Wray, Kari Stefansson, Peter M. Visscher, Douglas H.R. Blackwood, Ariel Darvasi, Enrico Domenici, Michael Gill, Hugh Gurling, Christina M. Hultman, Assen V. Jablensky, Kenneth S. Kendler, Jo Knight, Qingqin S. Li, Jianjun Liu, Steven A. McCarroll, Jennifer L. Moran, Michael J. Owen, Carlos N. Pato, Danielle Posthuma, Pamela Sklar, Jens R. Wendland, Mark J. Daly, Michael C. O’Donovan, Peter Donnelly, Ines Barroso, Jenefer M. Blackwell, Matthew A. Brown, Juan P. Casas, Panos Deloukas, Audrey Duncanson, Janusz Jankowski, Hugh S. Markus, Christopher G. Mathew, Colin N.A. Palmer, Robert Plomin, Anna Rautanen, Stephen J. Sawcer, Richard C. Trembath, Ananth C. Viswanathan, Nicholas W. Wood, Gavin Band, Céline Bellenguez, Colin Freeman, Eleni Giannoulatou, Garrett Hellenthal, Richard Pearson, Matti Pirinen, Amy Strange, Zhan Su, Damjan Vukcevic, Cordelia Langford, Hannah Blackburn, Suzannah J. Bumpstead, Serge Dronov, Sarah Edkins, Matthew Gillman, Emma Gray, Rhian Gwilliam, Naomi Hammond, Sarah E. Hunt, Alagurevathi Jayakumar, Jennifer Liddle, Owen T. McCann, Simon C. Potter, Radhi Ravindrarajah, Michelle Ricketts, Avazeh Tashakkori-Ghanbaria, Matthew Waller, Paul Weston, Pamela Whittaker, Sara Widaa, Mark I. McCarthy, Maria J. Arranz, Steven Bakker, Stephan Bender, Benedicto Crespo-Facorro, Jeremy Hall, Conrad Iyegbe, Stephen Lawrie, Kuang Lin, Don H. Linszen, Ignacio Mata, Muriel Walshe, Matthias Weisbrod, Durk Wiersma, Vassily Trubetskoy, Yunpeng Wang, Jonathan R.I. Coleman, Héléna A. Gaspar, Christiaan A. de Leeuw, Jennifer M. Whitehead Pavlides, Maciej Trzaskowski, Enda M. Byrne, Liam Abbott, Huda Akil, Diego Albani, Ney Alliey-Rodriguez, Adebayo Anjorin, Verneri Antilla, Swapnil Awasthi, Judith A. Badner, Marie Bækvad-Hansen, Jack D. Barchas, Nicholas Bass, Michael Bauer, Richard Belliveau, Carsten Bøcker Pedersen, Erlend Bøen, Marco P. Boks, James Boocock, Monika Budde, William Bunney, Margit Burmeister, Jonas Bybjerg-Grauholm, Miquel Casas, Felecia Cerrato, Kimberly Chambert, Alexander W. Charney, Danfeng Chen, Claire Churchhouse, Toni-Kim Clarke, William Coryell, David W. Craig, Cristiana Cruceanu, Piotr M. Czerski, Anders M. Dale, Simone de Jong, Jurgen Del-Favero, J. Raymond DePaulo, Amanda L. Dobbyn, Ashley Dumont, Torbjørn Elvsåshagen, Chun Chieh Fan, Sascha B. Fischer, Matthew Flickinger, Tatiana M. Foroud, Liz Forty, Christine Fraser, Katrin Gade, Diane Gage, Julie Garnham, Claudia Giambartolomei, Marianne Giørtz Pedersen, Jaqueline Goldstein, Scott D. Gordon, Katherine Gordon-Smith, Elaine K. Green, Melissa J. Green, Tiffany A. Greenwood, Weihua Guan, Martin Hautzinger, Urs Heilbronner, Maria Hipolito, Dominic Holland, Laura Huckins, Jessica S. Johnson, Radhika Kandaswamy, Robert Karlsson, Sarah Kittel-Schneider, Anna C. Koller, Ralph Kupka, Catharina Lavebratt, Jacob Lawrence, William B. Lawson, Markus Leber, Phil H. Lee, Shawn E. Levy, Jun Z. Li, Chunyu Liu, Anna Maaser, Donald J. MacIntyre, Pamela B. Mahon, Lina Martinsson, Steve McCarroll, Peter McGuffin, Melvin G. McInnis, James D. McKay, Helena Medeiros, Sarah E. Medland, Fan Meng, Grant W. Montgomery, Thomas W. Mühleisen, Hoang Nguyen, Caroline M. Nievergelt, Annelie Nordin Adolfsson, Evaristus A. Nwulia, Claire O'Donovan, Loes M. Olde Loohuis, Anil P.S. Ori, Lilijana Oruc, Urban Ösby, Amy Perry, Andrea Pfennig, Eline J. Regeer, Céline S. Reinbold, John P. Rice, Fabio Rivas, Margarita Rivera, Euijung Ryu, Cristina Sánchez-Mora, Alan F. Schatzberg, William A. Scheftner, Nicholas J. Schork, Cynthia Shannon Weickert, Tatyana Shehktman, Paul D. Shilling, Claire Slaney, Janet L. Sobell, Christine Søholm Hansen, Anne T. Spijker, Michael Steffens, John S. Strauss, Szabolcs Szelinger, Robert C. Thompson, Thorgeir E. Thorgeirsson, Jens Treutlein, Helmut Vedder, Weiqing Wang, Stanley J. Watson, Thomas W. Weickert, Simon Xi, Wei Xu, Allan H. Young, Peter Zandi, Peng Zhang, Sebastian Zöllner, Abdel Abdellaoui, Tracy M. Air, Till F.M. Andlauer, Silviu-Alin Bacanu, Aartjan T.F. Beekman, Elisabeth B. Binder, Julien Bryois, Henriette N. Buttenschøn, Na Cai, Enrique Castelao, Jane Hvarregaard Christensen, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Gregory E. Crawford, Gail Davies, Ian J. Deary, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Jerome C. Foo, Fernando S. Goes, Lynsey S. Hall, Thomas F. Hansen, Ian B. Hickie, Georg Homuth, Carsten Horn, David M. Howard, Marcus Ising, Rick Jansen, Ian Jones, Lisa A. Jones, Eric Jorgenson, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Dean F. MacKinnon, Robert M. Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Christel M. Middeldorp, Evelin Mihailov, Francis M. Mondimore, Sara Mostafavi, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O'Reilly, Hogni Oskarsson, Jodie N. Painter, Roseann E. Peterson, Wouter J. Peyrot, Giorgio Pistis, Jorge A. Quiroz, Per Qvist, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Stanley I. Shyn, Grant C.B. Sinnamon, Johannes H. Smit, Daniel J. Smith, Katherine E. Tansey, Henning Teismann, Wesley Thompson, Pippa A. Thomson, Matthew Traylor, André G. Uitterlinden, Daniel Umbricht, Albert M. van Hemert, Shantel Marie Weinsheimer, Jürgen Wellmann, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Klaus Berger, Udo Dannlowski, Katharina Domschke, Caroline Hayward, Andrew C. Heath, Stefan Kloiber, Glyn Lewis, Pamela AF. Madden, Patrik K. Magnusson, Preben Bo Mortensen, Michael C. O'Donovan, Sara A. Paciga, Nancy L. Pedersen, David J. Porteous, Catherine Schaefer, Henry Völzke, Marco Bortolato, Janita Bralten, Cynthia M. Bulik, Christie L. Burton, Caitlin E. Carey, Lea K. Davis, Laramie E. Duncan, Howard J. Edenberg, Lauren Erdman, Stephen V. Faraone, Slavina B. Goleva, Wei Guo, Christopher Hübel, Laura M. Huckins, Ekaterina A. Khramtsova, Joanna Martin, Carol A. Mathews, Elise Robinson, Eli Stahl, Barbara E. Stranger, Michela Traglia, Raymond K. Walters, Lauren A. Weiss, Stacey J. Winham, Yin Yao, Kristjar Skajaa, Markus Nöthen, Michael Owen, Robert H. Yolken, Niels Plath, Jonathan Mill, Daniel Geschwind, Psychiatry 1, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Centre of Excellence in Complex Disease Genetics, Research Programme of Molecular Medicine, Research Programs Unit, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, Functional Genomics, Biological Psychology, APH - Mental Health, APH - Methodology, Sociology and Social Gerontology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Blokland, Gabriella AM, Grove, Jakob, Chen, Chia Yen, Cotsapas, Chris, Tobet, Stuart, Handa, Robert, Lee, Sang Hong, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Sex Differences Cross-Disorder Analysis Group of the Psychiatric Genomics Consortium, iPSYCH, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Human genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), Child and Adolescent Psychiatry / Psychology, Adult Psychiatry, ANS - Complex Trait Genetics, and ANS - Mood, Anxiety, Psychosis, Stress & Sleep
Subjects: 0301 basic medicine, Male, Bipolar Disorder, Schizophrenia/genetics, LD SCORE REGRESSION, Genome-wide association study, 0302 clinical medicine, Receptors, SCHIZOPHRENIA, Psychotic Disorders/genetics, KYNURENINE PATHWAY METABOLISM, Genetics, RISK, Sex Characteristics, Vascular Endothelial Growth Factor, Bipolar Disorder/genetics, Major/genetics, Single Nucleotide, AFFECTIVE STIMULI IMPACT, Schizophrenia, Sulfurtransferases, Major depressive disorder, Female, Depressive Disorder, Major/genetics, Bipolar disorder, Locus (genetics), Genomics, Biology, Polymorphism, Single Nucleotide, Article, DYSPHORIC MOOD, 03 medical and health sciences, Sex differences, medicine, Humans, Genetic Predisposition to Disease, ddc:610, Polymorphism, GENOME-WIDE ASSOCIATION, Genotype-by-sex interaction, Biological Psychiatry, Depressive Disorder, Major, Depressive Disorder, GENDER-DIFFERENCES, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], PARAVENTRICULAR NUCLEUS, 3112 Neurosciences, Endothelial Cells, MAJOR DEPRESSION, medicine.disease, Genetic architecture, 030104 developmental biology, Mood, Receptors, Vascular Endothelial Growth Factor, Psychotic Disorders, 3111 Biomedicine, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Contains fulltext : 248656.pdf (Publisher’s version ) (Closed access) BACKGROUND: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. METHODS: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. RESULTS: Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10(-8)), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10(-6)) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10(-7); rs73033497, p = 8.8 × 10(-7); rs7914279, p = 6.4 × 10(-7)), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10(-7)) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10(-7)), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10(-7)) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). CONCLUSIONS: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.
Published: 2022
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22. Lack of support for the genes by early environment interaction hypothesis in the pathogenesis of schizophrenia

Author: Cathryn M. Lewis, Robin M. Murray, Christina M. Hultman, Mirella Ruggeri, Sarah E. Bergen, Michael Conlon O'Donovan, Sarah Tosato, Jiaqi Kou, Charlotte Dennison, Patrick F. Sullivan, Evangelos Vassos, Muriel Walshe, Gerome Breen, James T.R. Walters, Sophie E. Legge, Jessye Maxwell, Elvira Bramon, and Michael John Owen
Subjects: Psychosis, AcademicSubjects/MED00810, Birth weight, Bioinformatics, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Medicine, psychosis, Gene–environment interaction, placenta biology, Gene, 030304 developmental biology, 0303 health sciences, Pregnancy, business.industry, gene environment interaction, obstetric complications, medicine.disease, early life events, Psychiatry and Mental health, Schizophrenia, Cohort, polygenic risk score, business, 030217 neurology & neurosurgery, Regular Articles
Abstract: Ursini et al reported recently that the liability of schizophrenia explained by a polygenic risk score (PRS) derived from the variants most associated with schizophrenia was increased 5-fold in individuals who experienced complications during pregnancy or birth. Follow-up gene expression analysis showed that the genes mapping to the most associated genetic variants are highly expressed in placental tissues. If confirmed, these findings will have major implications in our understanding of the joint effect of genes and environment in the pathogenesis of schizophrenia. We examined the interplay between PRS and obstetric complications (OCs) in 5 independent samples (effective N = 2110). OCs were assessed with the full or modified Lewis-Murray scale, or with birth weight < 2.5 kg as a proxy. In a large cohort we tested whether the pathways from placenta-relevant variants in the original report were associated with case-control status. Unlike in the original study, we did not find significant effect of PRS on the presence of OCs in cases, nor a substantial difference in the association of PRS with case-control status in samples stratified by the presence of OCs. Furthermore, none of the PRS by OCs interactions were significant, nor were any of the biological pathways, examined in the Swedish cohort. Our study could not support the hypothesis of a mediating effect of placenta biology in the pathway from genes to schizophrenia. Methodology differences, in particular the different scales measuring OCs, as well as power constraints for interaction analyses in both studies, may explain this discrepancy.
Published: 2022

23. The Independent Effects of Psychosocial Stressors on Subclinical Psychosis: Findings from the Multinational EU-GEI Study

Author: Andrea Tortelli, Peter B. Jones, Jim van Os, Caterina La Cascia, Bart P. F. Rutten, Eva Velthorst, Baptiste Pignon, Celso Arango, Sarah Tosato, Lieuwe de Haan, Julio Sanjuán, Marion Leboyer, James B. Kirkbride, Antonio Lasalvia, Diego Quattrone, Cristina Marta Del-Ben, Andrei Szöke, Grégoire Baudin, Charlotte Gayer-Anderson, Pierre-Michel Llorca, Paulo Rossi Menezes, Robin M. Murray, Julio Bobes, Hannah E Jongsma, Miguel Bernardo, Mohamed Lajnef, Jean-Paul Selten, Hugo Peyre, Jean-Romain Richard, Franck Schürhoff, Craig Morgan, Marta Di Forti, Ilaria Tarricone, Mauro Braca, Manuel Arrojo, Aziz Ferchiou, Pignon, B., Lajnef, M., Kirkbride, J.B., Peyre, H., Ferchiou, A., Richard, J.-R., Baudin, G., Tosato, S., Jongsma, H., De Haan, L., Tarricone, I., Bernardo, M., Velthorst, E., Braca, M., Arango, C., Arrojo, M., Bobes, J., Del-Ben, C.M., Di Forti, M., Gayer-Anderson, C., Jones, P.B., La Cascia, C., Lasalvia, A., Menezes, P.R., Quattrone, D., Sanjuán, J., Selten, J.-P., Tortelli, A., Llorca, P.-M., Van Os, J., Rutten, B.P.F., Murray, R.M., Morgan, C., Leboyer, M., Szöke, A., Schürhoff, F., Pôle de Psychiatrie [Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital H. Mondor - A. Chenevier, Adult Psychiatry, APH - Mental Health, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Pignon B., Lajnef M., Kirkbride J.B., Peyre H., Ferchiou A., Richard J.-R., Baudin G., Tosato S., Jongsma H., De Haan L., Tarricone I., Bernardo M., Velthorst E., Braca M., Arango C., Arrojo M., Bobes J., Del-Ben C.M., Di Forti M., Gayer-Anderson C., Jones P.B., La Cascia C., Lasalvia A., Menezes P.R., Quattrone D., Sanjuan J., Selten J.-P., Tortelli A., Llorca P.-M., Van Os J., Rutten B.P.F., Murray R.M., Morgan C., Leboyer M., Szoke A., Schurhoff F., Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), and RS: MHeNs - R3 - Neuroscience
Subjects: Male, stressful life events, Schizotypy, positive subclinical symptom, Ethnic group, Social Environment, subclinical psychosis, positive subclinical symptoms, 0302 clinical medicine, Adverse Childhood Experiences, Settore MED/48 -Scienze Infermierist. e Tecn. Neuro-Psichiatriche e Riabilitat, SINTOMAS PSÍQUICOS, subclinical psychosi, 10. No inequality, COMMUNITY ASSESSMENT, Subclinical infection, GENERAL-POPULATION, psychotic symptom, Depression, Confounding, Social Discrimination, depressive subclinical symptom, stressful life event, ETHNIC-GROUPS, 3. Good health, Psychiatry and Mental health, NEIGHBORHOOD CHARACTERISTICS, ADULT PSYCHIATRIC-DISORDERS, psychotic symptoms, Adverse Childhood Experience, Female, psychosocial stress, Psychology, Psychosocial, Human, Clinical psychology, negative subclinical symptom, psychosocial stre, Adult, Psychosis, Sibling, LIFE EVENTS, schizotypy, Psychotic Disorder, 03 medical and health sciences, Community Assessment of Psychic Experiences (CAPE), THREATENING EXPERIENCES, medicine, Humans, European Union, Settore MED/25 - Psichiatria, childhood trauma, Siblings, Stressor, medicine.disease, PERCEIVED DISCRIMINATION, negative subclinical symptoms, 030227 psychiatry, PSYCHOMETRIC PROPERTIES, Psychotic Disorders, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, dis crimination, social capital, depressive subclinical symptoms, Stress, Psychological, 030217 neurology & neurosurgery, Regular Articles, discrimination
Abstract: The influence of psychosocial stressors on psychosis risk has usually been studied in isolation and after the onset of the disorder, potentially ignoring important confounding relationships or the fact that some stressors that may be the consequence of the disorder rather than preexisting. The study of subclinical psychosis could help to address some of these issues. In this study, we investigated whether there was (i) an association between dimensions of subclinical psychosis and several psychosocial stressors including: childhood trauma, self-reported discrimination experiences, low social capital, and stressful life experiences, and (ii) any evidence of environment-environment (ExE) interactions between these factors. Data were drawn from the EUGEI study, in which healthy controls (N = 1497) and siblings of subjects with a psychotic disorder (N = 265) were included in six countries. The association between psychosocial stressors and subclinical psychosis dimensions (positive, negative and depressive dimension as measured by the Community Assessment of Psychic Experiences (CAPE) scale) and possible ExE interactions were assessed using linear regression models. After adjusting for sex, age, ethnicity, country, and control/sibling status, childhood trauma (beta for positive dimension: 0.13, negative: 0.49, depressive: 0.26) and stressful life events (positive: 0.08, negative: 0.16, depressive: 0.17) were associated with the three dimensions. Lower social capital was associated with the negative and depression dimensions (negative: 0.26, depressive: 0.13), and self-reported discrimination experiences with the positive dimension (0.06). Our findings are in favor of independent, cumulative and non-specific influences of social adversities in subclinical psychosis in non-clinical populations, without arguments for E * E interactions. © The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Published: 2021
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24. The relationship of symptom dimensions with premorbid adjustment and cognitive characteristics at first episode psychosis: Findings from the EU-GEI study

Author: James B. Kirkbride, Hannah E. Jongsma, Alastair G. Cardno, Paulo Rossi Menezes, Andrea Quattrone, Pierre-Michel Llorca, Jose Luis Santos, Ilaria Tarricone, F. Seminerio, Charlotte Gayer-Anderson, Lucia Sideli, Roberto Muratori, Daniele La Barbera, G Tripoli, Teresa Sánchez-Gutiérrez, Jim van Os, Bart P. F. Rutten, Miguel Bernardo, Marta Di Forti, Robin M. Murray, Sarah Tosato, Julio Sanjuán, Lieuwe de Haan, Manuel Arrojo, Crocettarachele Sartorio, Eva Velthorst, Andrei Szöke, Antonio Lasalvia, Julio Bobes, Diego Quattrone, Craig Morgan, Ulrich Reininghaus, Victoria Rodriguez, Evangelos Vassos, Jean-Paul Selten, Giovanna Marrazzo, Caterina La Cascia, Celso Arango, Cristina Marta Del-Ben, Andrea Tortelli, Laura Ferraro, Peter B. Jones, RS: MHeNs - R3 - Neuroscience, Psychiatrie & Neuropsychologie, MUMC+: MA Psychiatrie (3), RS: MHeNs - R2 - Mental Health, Università degli studi di Palermo - University of Palermo, Faculty of Health Science, Universidad Internacional de la Rioja (UNIR), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Department of Psychiatry, Psychiatric Genetic Group, Instituto de Investigación Sanitaria de Santiago de Compostela, Complejo Hospitalario Universitario de Santiago de Compostela, Barcelona Clinic Schizophrenia Unit, Department of Medicine, Neuroscience Institute, Hospital clinic, University of Barcelona, IDIBAPS, CIBERSAM, Department of Medicine, Psychiatry Area, School of Medicine, Universidad de Oviedo, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Universidade de São Paulo Medical School (FMUSP), Department of Health Service and Population Research, Institute of Psychiatry, King's College London, Psylife Group, Division of Psychiatry, University College London, 6th Floor, Maple House, Section of Psychiatry, Azienda Ospedaliera Universitaria Integrata di Verona, Università degli studi di Verona = University of Verona (UNIVR), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Department of Preventive Medicine, Faculdade de Medicina, Universidade of São Paulo, Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, South Limburg Mental Health Research and Teaching Network, Maastricht University Medical Centre, Department of Psychiatry, Servicio de Psiquiatría Hospital 'Virgen de la Luz', Universitat de València (UV), Rivierduinen Institute for Mental Health Care, Institut National de la Santé et de la Recherche Médicale (INSERM), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Dapertment of Mental Health and pathological addictions, Bologna Local Health Authority, Etablissement Public de Santé Maison Blanche, Department of Psychiatry, Early Psychosis Section, Amsterdam UMC, University of Amsterdam, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, National Health Service, Villa Betania Institute, Department of Psychiatry, University of Cambridge, Cambridge, UK, Department Psychiatry, Brain Centre Rudolf Magnus, Utrecht University Medical Centre, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Department of Psychiatry, Early Psychosis Section, Academic Medical Centre, University of Amsterdam, Institute of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, University of Leeds, South London and Maudsley NHS Mental Health Foundation Trust, Tournayre, Christophe, Ferraro L., La Cascia C., La Barbera D., Sanchez-Gutierrez T., Tripoli G., Seminerio F., Sartorio C., Marrazzo G., Sideli L., Arango C., Arrojo M., Bernardo M., Bobes J., Del-Ben C.M., Gayer-Anderson C., Jongsma H.E., Kirkbride J.B., Lasalvia A., Tosato S., Llorca P.-M., Menezes P.R., Rutten B.P., Santos J.L., Sanjuan J., Selten J.-P., Szoke A., Tarricone I., Muratori R., Tortelli A., Velthorst E., Rodriguez V., Quattrone A., Jones P.B., Van Os J., Vassos E., Morgan C., de Haan L., Reininghaus U., Cardno A.G., Di Forti M., Murray R.M., Quattrone D., Jones, Peter [0000-0002-0387-880X], Apollo - University of Cambridge Repository, University College of London [London] (UCL), University of Cambridge [UK] (CAM), Adult Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, and Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep
Subjects: Psychosis, First episode psychosis, cognitive domains, Premorbid Adjustment Scale, QUOCIENTE DE INTELIGÊNCIA, Transdiagnostic Premorbid adjustment, NEGATIVE SYMPTOMS, Article, symptom dimensions, premorbid adjustment, WORKING-MEMORY, Secondary analysis, first episode psychosis, 1ST-EPISODE NONAFFECTIVE PSYCHOSIS, Medicine, Scopus, Cognitive domain, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Settore MED/25 - Psichiatria, Biological Psychiatry, Transdiagnostic, business.industry, Working memory, Confounding, Cognitive domains, Cognition, BIPOLAR DISORDER, Symptom dimensions, medicine.disease, GENE-ENVIRONMENT INTERACTIONS, First episode psychosi, CANNABIS USE, Psychiatry and Mental health, Symptom dimension, Perceptual reasoning, JCR, IQ, SOCIAL COGNITION, transdiagnostic, PROCESSING-SPEED, NEURODEVELOPMENTAL TRAJECTORIES, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Premorbid adjustment, business, SCHIZOAFFECTIVE DISORDER, Clinical psychology
Abstract: Premorbid functioning and cognitive measures may reflect gradients of developmental impairment across diagnostic categories in psychosis. In this study, we sought to examine the associations of current cognition and premorbid adjustment with symptom dimensions in a large first episode psychosis (FEP) sample. We used data from the international EU-GEI study. Bifactor modelling of the Operational Criteria in Studies of Psychotic Illness (OPCRIT) ratings provided general and specific symptom dimension scores. Premorbid Adjustment Scale estimated premorbid social (PSF) and academic adjustment (PAF), and WAIS-brief version measured IQ. A MANCOVA model examined the relationship between symptom dimensions and PSF, PAF, and IQ, having age, sex, country, self-ascribed ethnicity and frequency of cannabis use as confounders. In 785 patients, better PSF was associated with fewer negative (B=-0.12, 95% C.I. -0.18, -0.06, p
Published: 2021
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25. Depression is associated with increased disease activity and higher disability in a large Italian cohort of patients with rheumatoid arthritis

Author: S. Tomassi, Antonio Carletto, Maurizio Rossini, Sarah Tosato, Elena Fracassi, Cristian Caimmi, Sara Pezzato, Ilaria Montanari, Chiara Bonetto, Doriana Cristofalo, and Maria Giulia Gnatta
Subjects: Male, medicine.medical_specialty, Multivariate analysis, Diseases of the musculoskeletal system, Disease, Hospital Anxiety and Depression Scale, Arthritis, Rheumatoid, Cohort Studies, Rheumatology, Internal medicine, medicine, Humans, Disabled Persons, Disease activity, Rheumatoid arthritis, Depression (differential diagnoses), Disability, Depression, business.industry, Middle Aged, RC581-607, medicine.disease, Comorbidity, Italy, RC925-935, Cohort, Female, Immunologic diseases. Allergy, business
Abstract: Introduction Depression is a quite common comorbidity in patients with rheumatoid arthritis (RA) and is thought to influence its severity. This study aims to estimate, in a large cohort of Italian patients with RA, the prevalence of depression and to investigate the clinical correlates of depression in terms of disease activity and disability. Methods This is a cross-sectional study enrolling 490 outpatients with RA (80% female, mean age 59.5). The Hospital Anxiety and Depression Scale (HADS) was used to assess the presence of depression with a cut-off of 11. We collected data about disease activity and disability with DAS28, TJC-68, PhGA, PGA, VAS, DAS28, SDAI, CDAI and HAQ. Results Prevalence of depression was 14.3% (95% CI: 11-17%). Depressed patients, when compared with not depressed ones, were found to have higher scores for TJC-68 (p = 0.011), PhGA (p = 0.001), PGA (p = 0.001), VAS (p = 0.001), DAS28 (p = 0.007), SDAI (p = 0.001), CDAI (p = 0.001) and HAQ (p = 0.001). Out of the 70 depressed patients, 30 subjects, already known to be depressed in the past, were still depressed at the time of the assessment, with only 11 (15.7%) under antidepressants. A multivariate analysis showed that male sex, higher PGA score, use of antidepressants and higher HAQ score were significantly associated with an increased risk of depression. Conclusions Our study shows that depression is common in RA and may affect its activity mainly via an alteration in the perception of the disease. Although its important implications, depression is still under-diagnosed and its management is inadequate.
Published: 2021
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26. Correlations between immune and metabolic serum markers and schizophrenia/bipolar disorder polygenic risk score in first‐episode psychosis

Author: Angela Favaro, Sarah Tosato, Emanuela Leuci, Luisella Bocchio-Chiavetto, Giovanni de Girolamo, Antonio Lasalvia, Carlo Maj, Mirella Ruggeri, Roberta Zanardini, and Massimo Gennarelli
Subjects: Adult, Male, Multifactorial Inheritance, medicine.medical_specialty, Psychosis, Bipolar Disorder, Inflammation, Correlation, Young Adult, Immune system, Risk Factors, Internal medicine, first episode psychosis, medicine, Humans, Bipolar disorder, Chemokine CCL4, Biological Psychiatry, business.industry, medicine.disease, Ghrelin, Psychiatry and Mental health, Endocrinology, inflammation, metabolism, polygenic risk score, Case-Control Studies, Schizophrenia, Female, Polygenic risk score, Pshychiatric Mental Health, medicine.symptom, business, Biomarkers, Diagnosis of schizophrenia
Abstract: Aims There is a strong interest in identifying the biological mechanisms involved in the genetic risk for psychotic disorders. In this study, we evaluated the correlation between serum concentrations of specific molecular markers and the genetic component for schizophrenia and bipolar disorder. Methods We analysed the association between the polygenic risk score (PRS) and the serum levels of different inflammatory/metabolic markers in a sample of 81 first-episode psychosis patients (FEP) with a diagnosis of schizophrenia or bipolar disorder and 33 controls. Results A positive correlation of schizophrenia and bipolar disorder PRS with the inflammatory marker C-C Motif Chemokine Ligand 4 serum concentration (ρ = 0.42, P = 1.56 × 10-04 and ρ = 0.40, P = 1.65 × 10-03 , respectively) and a negative correlation with the serum ghrelin content (ρ = - 0.35, P = 4.27 × 10-03 and ρ = - 0.45, P = 6.05 × 10-04 , respectively) were observed. Conclusion These findings provide new insight into the biological underpinnings of the PRS component, thus supporting a role of the genetic liability on the inflammatory and metabolic alterations that characterize psychosis onset.
Published: 2019
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27. Use of multiple Polygenic Risk Scores for distinguishing Schizophrenia-spectrum disorder and Affective psychosis categories; the EUGEI study

Author: Robin M. Murray, Hannah E. Jongsma, Di Forti M, Evangelos Vassos, van os J, Manuel Arrojo, Jean-Paul Selten, Edoardo Spinazzola, Julio Bobes, Laura Ferraro, Ilaria Tarricone, Alameda L, La Barbera D, Pak C. Sham, Rodriguez, Peter B. Jones, Eva Velthorst, Giada Tripoli, Pierre-Michel Llorca, Alexander Richards, C. Arango, Stéphane Jamain, Elena Bonora, Simona A. Stilo, La Cascia C, Antonio Lasalvia, Craig Morgan, M O'Donovan, Diego Quattrone, Charlotte Gayer-Anderson, de Haan L, Miguel Bernardo, Trotta G, Bart P. F. Rutten, Sarah Tosato, and James B. Kirkbride
Subjects: Affective psychosis, Psychosis, Schizophrenia, business.industry, medicine, Polygenic risk score, Psychotic depression, Bipolar disorder, medicine.disease, business, Depression (differential diagnoses), Clinical psychology, Multinomial logistic regression
Abstract: Schizophrenia (SZ), Bipolar Disorder (BD) and Depression (D) run in families. This susceptibility is partly due to hundreds or thousands of common genetic variants, each conferring a fractional risk. The cumulative effects of the associated variants can be summarised as a polygenic risk score (PRS). Using data from the EUGEI case-control study, we aimed to test whether PRSs for three major psychiatric disorders (SZ, BD, D) and for intelligent quotient (IQ) as a neurodevelopmental proxy, can discriminate affective psychosis (AP) from schizophrenia-spectrum disorder (SSD). Participants (573 cases, 1005 controls) of european ancestry from 17 sites as part of the EUGEI study were successfully genotyped following standard quality control procedures. Using standardised PRS for SZ, BD, D, and IQ built from the latest available summary statistics, we performed simple or multinomial logistic regression models adjusted for 10 principal components for the different clinical comparisons. In case-control comparisons PRS-SZ, PRS-BD and PRS-D distributed differentially across psychotic subcategories. In case-case comparison, both PRS-SZ (OR=0.7, 95 %CI 0.53-0.92) and PRS-D (OR=1.29, 95%CI 1.05-1.6) differentiated global AP from SSD; and within AP categories, only PRS-SZ differentiated BD from psychotic depression (OR=2.38, 95%CI 1.32-4.29). Combining PRS for severe psychiatric disorders in prediction models for psychosis phenotypes can increase discriminative ability and improve our understanding of these phenotypes. Our results point towards potential usefulness of PRSs for diagnostic prediction in specific populations such as high-risk or early psychosis phases.
Published: 2021
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28. A Comparison of Ten Polygenic Score Methods for Psychiatric Disorders Applied Across Multiple Cohorts

Author: Guiyan Ni, Jian Zeng, Joana A. Revez, Ying Wang, Zhili Zheng, Tian Ge, Restuadi Restuadi, Jacqueline Kiewa, Dale R. Nyholt, Jonathan R.I. Coleman, Jordan W. Smoller, Jian Yang, Peter M. Visscher, Naomi R. Wray, Stephan Ripke, Benjamin M. Neale, Aiden Corvin, James T.R. Walters, Kai-How Farh, Peter A. Holmans, Phil Lee, Brendan Bulik-Sullivan, David A. Collier, Hailiang Huang, Tune H. Pers, Ingrid Agartz, Esben Agerbo, Margot Albus, Madeline Alexander, Farooq Amin, Silviu A. Bacanu, Martin Begemann, Richard A. Belliveau, Judit Bene, Sarah E. Bergen, Elizabeth Bevilacqua, Tim B. Bigdeli, Donald W. Black, Richard Bruggeman, Nancy G. Buccola, Randy L. Buckner, William Byerley, Wiepke Cahn, Guiqing Cai, Dominique Campion, Rita M. Cantor, Vaughan J. Carr, Noa Carrera, Stanley V. Catts, Kimberley D. Chambert, Raymond C.K. Chan, Ronald Y.L. Chen, Eric Y.H. Chen, Wei Cheng, Eric F.C. Cheung, Siow Ann Chong, C. Robert Cloninger, David Cohen, Nadine Cohen, Paul Cormican, Nick Craddock, James J. Crowley, Michael Davidson, Kenneth L. Davis, Franziska Degenhardt, Jurgen Del Favero, Ditte Demontis, Dimitris Dikeos, Timothy Dinan, Srdjan Djurovic, Gary Donohoe, Elodie Drapeau, Jubao Duan, Frank Dudbridge, Naser Durmishi, Peter Eichhammer, Johan Eriksson, Valentina Escott-Price, Laurent Essioux, Ayman H. Fanous, Martilias S. Farrell, Josef Frank, Lude Franke, Robert Freedman, Nelson B. Freimer, Marion Friedl, Joseph I. Friedman, Menachem Fromer, Giulio Genovese, Lyudmila Georgieva, Ina Giegling, Paola Giusti-Rodríguez, Stephanie Godard, Jacqueline I. Goldstein, Vera Golimbet, Srihari Gopal, Jacob Gratten, Lieuwe de Haan, Christian Hammer, Marian L. Hamshere, Mark Hansen, Thomas Hansen, Vahram Haroutunian, Annette M. Hartmann, Frans A. Henskens, Stefan Herms, Joel N. Hirschhorn, Per Hoffmann, Andrea Hofman, Mads V. Hollegaard, David M. Hougaard, Masashi Ikeda, Inge Joa, Antonio Julià, René S. Kahn, Luba Kalaydjieva, Sena Karachanak-Yankova, Juha Karjalainen, David Kavanagh, Matthew C. Keller, James L. Kennedy, Andrey Khrunin, Yunjung Kim, Janis Klovins, James A. Knowles, Bettina Konte, Vaidutis Kucinskas, Zita Ausrele Kucinskiene, Hana Kuzelova-Ptackova, Anna K. Kähler, Claudine Laurent, Jimmy Lee, S. Hong Lee, Sophie E. Legge, Bernard Lerer, Miaoxin Li, Tao Li, Kung-Yee Liang, Jeffrey Lieberman, Svetlana Limborska, Carmel M. Loughland, Jan Lubinski, Jouko Lönnqvist, Milan Macek, Patrik K.E. Magnusson, Brion S. Maher, Wolfgang Maier, Jacques Mallet, Sara Marsal, Manuel Mattheisen, Morten Mattingsdal, Robert W. McCarley, Colm McDonald, Andrew M. McIntosh, Sandra Meier, Carin J. Meijer, Bela Melegh, Ingrid Melle, Raquelle I. Mesholam-Gately, Andres Metspalu, Patricia T. Michie, Lili Milani, Vihra Milanova, Younes Mokrab, Derek W. Morris, Ole Mors, Kieran C. Murphy, Robin M. Murray, Inez Myin-Germeys, Bertram Müller-Myhsok, Mari Nelis, Igor Nenadic, Deborah A. Nertney, Gerald Nestadt, Kristin K. Nicodemus, Liene Nikitina-Zake, Laura Nisenbaum, Annelie Nordin, Eadbhard O’Callaghan, Colm O’Dushlaine, F. Anthony O’Neill, Sang-Yun Oh, Ann Olincy, Line Olsen, Jim Van Os, Psychosis Endophenotypes International Consortium, Christos Pantelis, George N. Papadimitriou, Sergi Papiol, Elena Parkhomenko, Michele T. Pato, Tiina Paunio, Milica Pejovic-Milovancevic, Diana O. Perkins, Olli Pietiläinen, Jonathan Pimm, Andrew J. Pocklington, John Powell, Alkes Price, Ann E. Pulver, Shaun M. Purcell, Digby Quested, Henrik B. Rasmussen, Abraham Reichenberg, Mark A. Reimers, Alexander L. Richards, Joshua L. Roffman, Panos Roussos, Douglas M. Ruderfer, Veikko Salomaa, Alan R. Sanders, Ulrich Schall, Christian R. Schubert, Thomas G. Schulze, Sibylle G. Schwab, Edward M. Scolnick, Rodney J. Scott, Larry J. Seidman, Jianxin Shi, Engilbert Sigurdsson, Teimuraz Silagadze, Jeremy M. Silverman, Kang Sim, Petr Slominsky, Hon-Cheong So, Chris C.A. Spencer, Eli A. Stahl, Hreinn Stefansson, Stacy Steinberg, Elisabeth Stogmann, Richard E. Straub, Eric Strengman, Jana Strohmaier, T. Scott Stroup, Mythily Subramaniam, Jaana Suvisaari, Dragan M. Svrakic, Jin P. Szatkiewicz, Erik Söderman, Srinivas Thirumalai, Draga Toncheva, Sarah Tosato, Juha Veijola, John Waddington, Dermot Walsh, Dai Wang, Qiang Wang, Bradley T. Webb, Mark Weiser, Dieter B. Wildenauer, Nigel M. Williams, Stephanie Williams, Stephanie H. Witt, Aaron R. Wolen, Emily H.M. Wong, Brandon K. Wormley, Hualin Simon Xi, Clement C. Zai, Xuebin Zheng, Fritz Zimprich, Kari Stefansson, Wellcome Trust Case-Control Consortium, Rolf Adolfsson, Ole A. Andreassen, Douglas H.R. Blackwood, Elvira Bramon, Joseph D. Buxbaum, Anders D. Børglum, Sven Cichon, Ariel Darvasi, Enrico Domenici, Hannelore Ehrenreich, Tõnu Esko, Pablo V. Gejman, Michael Gill, Hugh Gurling, Christina M. Hultman, Nakao Iwata, Assen V. Jablensky, Erik G. Jönsson, Kenneth S. Kendler, George Kirov, Jo Knight, Todd Lencz, Douglas F. Levinson, Qingqin S. Li, Jianjun Liu, Anil K. Malhotra, Steven A. McCarroll, Andrew McQuillin, Jennifer L. Moran, Preben B. Mortensen, Bryan J. Mowry, Markus M. Nöthen, Roel A. Ophoff, Michael J. Owen, Aarno Palotie, Carlos N. Pato, Tracey L. Petryshen, Danielle Posthuma, Marcella Rietschel, Brien P. Riley, Dan Rujescu, Pak C. Sham, Pamela Sklar, David St Clair, Daniel R. Weinberger, Jens R. Wendland, Thomas Werge, Mark J. Daly, Patrick F. Sullivan, Michael C. O’Donovan, Maciej Trzaskowski, Enda M. Byrne, Abdel Abdellaoui, Mark J. Adams, Tracy M. Air, Till F.M. Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Elisabeth B. Binder, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Enrique Castelao, Jane Hvarregaard Christensen, Toni-Kim Clarke, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Gregory E. Crawford, Gail Davies, Ian J. Deary, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Jerome C. Foo, Andreas J. Forstner, Héléna A. Gaspar, Fernando S. Goes, Scott D. Gordon, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Ian B. Hickie, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Howard, Marcus Ising, Rick Jansen, Ian Jones, Lisa A. Jones, Eric Jorgenson, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Peter McGuffin, Sarah E. Medland, Divya Mehta, Christel M. Middeldorp, Evelin Mihailov, Yuri Milaneschi, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Niamh Mullins, Matthias Nauck, Bernard Ng, Michel G. Nivard, Paul F. O’Reilly, Hogni Oskarsson, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Wouter J. Peyrot, Giorgio Pistis, Jorge A. Quiroz, Per Qvist, John P. Rice, Margarita Rivera, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Stanley I. Shyn, Grant C.B. Sinnamon, Johannes H. Smit, Daniel J. Smith, Fabian Streit, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G. Uitterlinden, Daniel Umbricht, Sandra Van der Auwera, Albert M. van Hemert, Alexander Viktorin, Yunpeng Wang, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Yang Wu, Hualin S. Xi, Futao Zhang, Volker Arolt, Bernhard T. Baune, Klaus Berger, Dorret I. Boomsma, Udo Dannlowski, E.J.C. de Geus, J. Raymond DePaulo, Katharina Domschke, Hans J. Grabe, Steven P. Hamilton, Caroline Hayward, Andrew C. Heath, Stefan Kloiber, Glyn Lewis, Susanne Lucae, Pamela A.F. Madden, Patrik K. Magnusson, Nicholas G. Martin, Preben Bo Mortensen, Merete Nordentoft, Sara A. Paciga, Nancy L. Pedersen, Adult Psychiatry, APH - Mental Health, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Ni, Guiyan, Zeng, Jian, Revez, Joana A., Wang, Ying, Zhili, Zheng, Ge, Tian, Restuadi, Restuadi, Kiewa, Jacqueline, Nyholt, Dale R, Coleman, Jonathan RI, Smoller, Jordan W, Lee, S Hong, APH - Methodology, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Econometrics, Psychiatry, Department of Technology and Operations Management, Child and Adolescent Psychiatry / Psychology, Epidemiology, Erasmus MC other, Urology, Internal Medicine, Medical Informatics, Immunology, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), and Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep
Subjects: 0301 basic medicine, Multifactorial Inheritance, medicine.medical_specialty, LDpred2, BF, Genomics, Disease, Major depressive disorder, risk prediction, 03 medical and health sciences, 0302 clinical medicine, MegaPRS, SDG 3 - Good Health and Well-being, medicine, Humans, Genetic Predisposition to Disease, ddc:610, Genetic risk, Psychiatry, Biological Psychiatry, Genetic association, Depressive Disorder, Major, business.industry, Mental Disorders, medicine.disease, Genetic architecture, Polygenic scores, Risk prediction, polygenic scores, PRS-CS, psychiatric disorders, 030104 developmental biology, SBayesR, Schizophrenia, Cohort, Lassosum, RC0321, business, Psychiatric disorders, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: BACKGROUND: Polygenic scores (PGSs), which assess the genetic risk of individuals for a disease, are calculated as a weighted count of risk alleles identified in genome-wide association studies. PGS methods differ in which DNA variants are included and the weights assigned to them; some require an independent tuning sample to help inform these choices. PGSs are evaluated in independent target cohorts with known disease status. Variability between target cohorts is observed in applications to real data sets, which could reflect a number of factors, e.g., phenotype definition or technical factors.METHODS: The Psychiatric Genomics Consortium Working Groups for schizophrenia and major depressive disorder bring together many independently collected case-control cohorts. We used these resources (31,328 schizophrenia cases, 41,191 controls; 248,750 major depressive disorder cases, 563,184 controls) in repeated application of leave-one-cohort-out meta-analyses, each used to calculate and evaluate PGS in the left-out (target) cohort. Ten PGS methods (the baseline PC+T method and 9 methods that model genetic architecture more formally: SBLUP, LDpred2-Inf, LDpred-funct, LDpred2, Lassosum, PRS-CS, PRS-CS-auto, SBayesR, MegaPRS) were compared.RESULTS: Compared with PC+T, the other 9 methods gave higher prediction statistics, MegaPRS, LDPred2, and SBayesR significantly so, explaining up to 9.2% variance in liability for schizophrenia across 30 target cohorts, an increase of 44%. For major depressive disorder across 26 target cohorts, these statistics were 3.5% and 59%, respectively.CONCLUSIONS: Although the methods that more formally model genetic architecture have similar performance, MegaPRS, LDpred2, and SBayesR rank highest in most comparisons and are recommended in applications to psychiatric disorders.
Published: 2021
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29. Migration history and risk of psychosis: results from the multinational EU-GEI study

Author: Iulio Sanjuán, Robin M. Murray, Els van der Ven, James B. Kirkbride, Hannah E Jongsma, Jean-Paul Selten, Manuel Arrojo, Julio Bobes, Andrei Szöke, Cristina Marta Del-Ben, Roberto Muratori, Jim van Os, Mara Parellada, Bart P. F. Rutten, Craig Morgan, Pierre-Michel Llorca, Marta Di Forti, Sarah Tosato, Peter B. Jones, Miguel Bernardo, Ilaria Tarricone, Simona A. Stilo, Jose Luis Santos, Federico Suprani, Conrad Iyegbe, Giuseppe D’Andrea, Eva Velthorst, Domenico Berardi, Paulo Rossi Menezes, Andrea Tortelli, Laura Ferraro, Antonio Lasalvia, Diego Quattrone, Caterina La Cascia, Celso Arango, Lieuwe de Haan, Charlotte Gayer-Anderson, Giada Tripoli, University of Bologna/Università di Bologna, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), University College of London [London] (UCL), University of Cambridge [UK] (CAM), Università degli studi di Verona = University of Verona (UNIVR), King‘s College London, Institute of Psychiatry, Psychology & Neuroscience, King's College London, Columbia University [New York], Department of Psychiatry and Neuropsychology [Maastricht], Maastricht University [Maastricht], VU University Medical Center [Amsterdam], Icahn School of Medicine at Mount Sinai [New York] (MSSM), Universidade de São Paulo = University of São Paulo (USP), Hospital General Universitario 'Gregorio Marañón' [Madrid], Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Università degli studi di Palermo - University of Palermo, Universidad de Oviedo [Oviedo], University of Barcelona, Complejo Hospitalario Universitario de Santiago de Compostela [Saint-Jacques-de-Compostelle, Espagne] (CHUS), Instituto de Investigación Sanitaria de Santiago de Compostela / Health Research Institute of Santiago de Compostela (IDIS), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre d'Investigation Clinique Henri Mondor (CIC Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), University Medical Center [Utrecht], Cambridgeshire & Peterborough NHS Foundation Trust [Cambridge] (CPFT), RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, MUMC+: MA Psychiatrie (3), RS: MHeNs - R3 - Neuroscience, Adult Psychiatry, APH - Mental Health, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Tarricone I., D'Andrea G., Jongsma H.E., Tosato S., Gayer-Anderson C., Stilo S.A., Suprani F., Iyegbe C., Van Der Ven E., Quattrone D., Di Forti M., Velthorst E., Rossi Menezes P., Arango C., Parellada M., Lasalvia A., La Cascia C., Ferraro L., Bobes J., Bernardo M., Sanjuan I., Santos J.L., Arrojo M., Del-Ben C.M., Tripoli G., Llorca P.-M., De Haan L., Selten J.-P., Tortelli A., Szoke A., Muratori R., Rutten B.P., Van Os J., Jones P.B., Kirkbride J.B., Berardi D., Murray R.M., Morgan C., Clinical Developmental Psychology, World Health Organization (WHO) Collaborating Center, and Tournayre, Christophe
Subjects: Psychosis, medicine.medical_specialty, ESTUDOS DE CASOS E CONTROLES, Ethnic group, Logistic regression, IMMIGRANTS, FAMILY-HISTORY, first-generation migrants, Odds, 03 medical and health sciences, 0302 clinical medicine, First-episode psychosi, first-generation migrant, SCHIZOPHRENIA, medicine, migration adversities, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 1ST-EPISODE PSYCHOSIS, INTERNAL MIGRATION, Applied Psychology, Cumulative effect, ComputingMilieux_MISCELLANEOUS, migration history, psychosis risk, business.industry, Public health, migration adversitie, SDG 10 - Reduced Inequalities, First-episode psychosis, medicine.disease, CHILDHOOD TRAUMA, 030227 psychiatry, 3. Good health, ETHNICITY, Psychiatry and Mental health, social disadvantages, Schizophrenia, Multinational corporation, 1ST-CONTACT INCIDENCE, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, MENTAL-HEALTH, SOCIAL DISADVANTAGE, 030217 neurology & neurosurgery, Demography
Abstract: The European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) Project was funded by grant agreement Health-F2-2010-241909 (Project EU-GEI) from the European Community’s Seventh Framework programme., Tarricone, I., D'Andrea, G., Jongsma, H.E., Tosato, S., Gayer-Anderson, C., Stilo, S.A., Suprani, F., Iyegbe, C., Van Der Ven, E., Quattrone, D., Di Forti, M., Velthorst, E., Rossi Menezes, P., Arango, C., Parellada, M., Lasalvia, A., La Cascia, C., Ferraro, L., Bobes, J., Bernardo, M., Sanjuán, I., Santos, J.L., Arrojo, M., Del-Ben, C.M., Tripoli, G., Llorca, P.-M., De Haan, L., Selten, J.-P., Tortelli, A., Szöke, A., Muratori, R., Rutten, B.P., Van Os, J., Jones, P.B., Kirkbride, J.B., Berardi, D., Murray, R.M., Morgan, C.
Published: 2021
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30. Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis

Author: Robin M. Murray, Luis Alameda, Andrea Tortelli, Laura Ferraro, Cristina Marta Del-Ben, Eva Velthorst, Peter B. Jones, Monica Aas, James B. Kirkbride, Pierre-Michel Llorca, Evangelos Vassos, Hannah E. Jongsma, Paola Dazzan, Jean-Paul Selten, Miguel Bernardo, Victoria Rodriguez, Lieuwe de Haan, Marta Di Forti, Jose Luis Santos, Roberto Muratori, Caterina La Cascia, Manuel Arrojo, Pak C. Sham, Jim van Os, Bart P. F. Rutten, Daniele La Barbera, Celso Arango, Ilaria Tarricone, Domenico Berardi, Sarah Tosato, Craig Morgan, Julio Bobes, Paulo Rossi Menezes, Antonella Trotta, Julio Sanjuán, Andrei Szöke, Antonio Lasalvia, Diego Quattrone, Charlotte Gayer-Anderson, Giada Tripoli, Aas M., Alameda L., Di Forti M., Quattrone D., Dazzan P., Trotta A., Ferraro L., Rodriguez V., Vassos E., Sham P., Tripoli G., La Cascia C., La Barbera D., Tarricone I., Muratori R., Berardi D., Lasalvia A., Tosato S., Szoke A., Llorca P.-M., Arango C., Tortelli A., De Haan L., Velthorst E., Bobes J., Bernardo M., Sanjuan J., Santos J.L., Arrojo M., Del-Ben C.M., Menezes P.R., Selten J.-P., Jones P.B., Jongsma H.E., Kirkbride J.B., Rutten B.P.F., Van Os J., Gayer-Anderson C., Murray R.M., Morgan C., Cascia C.L., Barbera D.L., RS: MHeNs - R3 - Neuroscience, Psychiatrie & Neuropsychologie, MUMC+: MA Psychiatrie (3), RS: MHeNs - R2 - Mental Health, MUMC+: Hersen en Zenuw Centrum (3), Adult Psychiatry, APH - Mental Health, ANS - Complex Trait Genetics, and ANS - Mood, Anxiety, Psychosis, Stress & Sleep
Subjects: SCHIZOPHRENIA SPECTRUM, medicine.medical_specialty, GENES, polygenic risk, first-episode psychosi, ILLNESS, interaction contrast ratio, Childhood trauma, DOPAMINE, First episode psychosis, Settore MED/48 -Scienze Infermierist. e Tecn. Neuro-Psichiatriche e Riabilitat, MALTREATMENT, Medicine, first-episode psychosis, ABUSE, Psychiatry, Settore MED/25 - Psichiatria, Applied Psychology, TRAUMA, ENVIRONMENT, business.industry, medicine.disease, schizophrenia, Psychiatry and Mental health, Schizophrenia, RELIABILITY, Polygenic risk score, synergistic effects, business
Abstract: The European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) Project is funded by grant agreement HEALTH-F2-2010-241909 (Project EU-GEI) from the European Community’s Seventh Framework Programme., Aas, M; Alameda, L; Di Forti, M; Quattrone, D; Dazzan, P; Trotta, A; Ferraro, L; Rodriguez, V; Vassos, E; Sham, P; Tripoli, G; La Cascia, C; La Barbera, D; Tarricone, I; Muratori, R; Berardi, D; Lasalvia, A; Tosato, S; Szoke, A; Llorca, PM; Arango, C; Tortelli, A; de Haan, L; Velthorst, E; Bobes, J; Bernardo, M; Sanjuan, J; Santos, JL; Arrojo, M; Del-Ben, CM; Menezes, PR; Selten, JP; Jones, PB; Jongsma, HE; Kirkbride, JB; Rutten, BPF; van Os, J; Gayer-Anderson, C; Murray, RM; Morgan, C
Published: 2021

31. Duration of untreated psychosis in first-episode psychosis is not associated with common genetic variants for major psychiatric conditions: results from the multi-center EU-GEI Study

Author: Olesya Ajnakina, Caterina La Cascia, James B. Kirkbride, Evangelos Vassos, Cristina Marta Del-Ben, Celso Arango, Charlotte Gayer-Anderson, Julio Bobes, Lieuwe de Haan, Jean-Paul Selten, Andrei Szöke, Julio Sanjuán, Miguel Bernardo, Paulo Rossi Menezes, Manuel Arrojo Romero, I. Tarricone, Hannah E. Jongsma, Jim van Os, Bart P. F. Rutten, Jose Luis Santos, Eva Velthorst, Marta Di Forti, Sarah Tosato, Peter B. Jones, Pierre-Michel Llorca, Alexander Richards, Andrea Tortelli, Giuseppe D’Andrea, Victoria Rodriguez, Robin M. Murray, M O'Donovan, Domenico Berardi, Antonio Lasalvia, Diego Quattrone, Adult Psychiatry, APH - Mental Health, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Psychiatrie & Neuropsychologie, MUMC+: MA Psychiatrie (3), RS: MHeNs - R3 - Neuroscience, RS: MHeNs - R2 - Mental Health, MUMC+: Hersen en Zenuw Centrum (3), Ajnakina O., Rodriguez V., Quattrone D., Di Forti M., Vassos E., Arango C., Berardi D., Bernardo M., Bobes J., De Haan L., Del-Ben C.M., Gayer-Anderson C., Jongsma H.E., Lasalvia A., Tosato S., Llorca P.-M., Menezes P.R., Rutten B.P., Santos J.L., Sanjuan J., Selten J.-P., Szoke A., Tarricone I., D'andrea G., Richards A., Tortelli A., Velthorst E., Jones P.B., Arrojo Romero M., La Cascia C., Kirkbride J.B., Van Os J., O'donovan M., and Murray R.M.
Subjects: Bipolar Disorder, Time Factors, Intelligence, Genome-wide association study, DETERMINANTS, psychosi, 0302 clinical medicine, Interquartile range, Settore MED/48 -Scienze Infermierist. e Tecn. Neuro-Psichiatriche e Riabilitat, IMPUTATION, polygenic score, psychosis, 0303 health sciences, Confounding, Europe, Psychiatry and Mental health, genome-wide association studie, Schizophrenia, Major depressive disorder, lipids (amino acids, peptides, and proteins), Case-Control Studie, duration of untreated psychosis, Brazil, Human, Adult, Psychosis, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Time Factor, AcademicSubjects/MED00810, DISORDERS, 1ST EPISODE, ILLNESS, Psychotic Disorder, duration of untreated psychosi, 03 medical and health sciences, Internal medicine, medicine, Humans, Bipolar disorder, GENOME-WIDE ASSOCIATION, Settore MED/25 - Psichiatria, METAANALYSIS, 030304 developmental biology, Depressive Disorder, Major, business.industry, COMPONENTS, TREATMENT DELAY, medicine.disease, TRANSTORNO BIPOLAR, schizophrenia, polygenic scores, Psychotic Disorders, Case-Control Studies, dup, genome-wide association studies, business, 030217 neurology & neurosurgery, Regular Articles, Genome-Wide Association Study
Abstract: The EU-GEI Project is funded by the European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-2010–241909 (Project EU-GEI)., Ajnakina, O., Rodriguez, V., Quattrone, D., Di Forti, M., Vassos, E., Arango, C., Berardi, D., Bernardo, M., Bobes, J., De Haan, L., Del-Ben, C.M., Gayer-Anderson, C., Jongsma, H.E., Lasalvia, A., Tosato, S., Llorca, P.-M., Menezes, P.R., Rutten, B.P., Santos, J.L., Sanjuán, J., Selten, J.-P., Szöke, A., Tarricone, I., D'andrea, G., Richards, A., Tortelli, A., Velthorst, E., Jones, P.B., Arrojo Romero, M., La Cascia, C., Kirkbride, J.B., Van Os, J., O'donovan, M., Murray, R.M.
Published: 2021
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32. A comparison of ten polygenic score methods for psychiatric disorders applied across multiple cohorts

Author: Sarah TOSATO, Tracy Air, Eske Derks, Inez Myin-Germeys, Jonathan Coleman, Per Qvist, Lucía Colodro Conde, Robert Freedman, Donald Black, Guiyan Ni, Glyn Lewis, Bryan Mowry, Ulrich Schall, Kang Sim, Rodney Scott, Joana A. Revez, and Bradley Webb
Subjects: medicine.medical_specialty, Receiver operating characteristic, business.industry, Genome-wide association study, Disease, Explained variation, medicine.disease, Schizophrenia, Cohort, medicine, Major depressive disorder, Psychiatry, business, Genetic association
Abstract: BackgroundPolygenic scores (PGSs), which assess the genetic risk of individuals for a disease, are calculated as a weighted count of risk alleles identified in genome-wide association studies (GWASs). PGS methods differ in which DNA variants are included and the weights assigned to them; some require an independent tuning sample to help inform these choices. PGSs are evaluated in independent target cohorts with known disease status. Variability between target cohorts is observed in applications to real data sets, which could reflect a number of factors, e.g., phenotype definition or technical factors.MethodsThe Psychiatric Genomics Consortium working groups for schizophrenia (SCZ) and major depressive disorder (MDD) bring together many independently collected case- control cohorts. We used these resources (31K SCZ cases, 41K controls; 248K MDD cases, 563K controls) in repeated application of leave-one-cohort-out meta-analyses, each used to calculate and evaluate PGS in the left-out (target) cohort. Ten PGS methods (the baseline PC+T method and nine methods that model genetic architecture more formally: SBLUP, LDpred2-Inf, LDpred-funct, LDpred2, Lassosum, PRS-CS, PRS-CS-auto, SBayesR, MegaPRS) are compared.ResultsCompared to PC+T, the other nine methods give higher prediction statistics, MegaPRS, LDPred2 and SBayesR significantly so, up to 9.2% variance in liability for SCZ across 30 target cohorts, an increase of 44%. For MDD across 26 target cohorts these statistics were 3.5% and 59%, respectively.ConclusionsAlthough the methods that more formally model genetic architecture have similar performance, MegaPRS, LDpred2, and SBayesR rank highest in most comparison and are recommended in applications to psychiatric disorders.
Published: 2020
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33. Obstetric Complications and Polygenic Risk Score: Which Role in Predicting a Severe Short-Term Outcome in Psychosis?

Author: Sarah Tosato, Chiara Bonetto, Evangelos Vassos, Antonio Lasalvia, Katia De Santi, Margherita Gelmetti, Doriana Cristofalo, Alexander Richards, Mirella Ruggeri, and on behalf of the PICOS-Veneto Group
Subjects: Adult, Male, psychosis, polygenic risk score, outcome, obstetric complications, Multifactorial Inheritance, Pediatrics, medicine.medical_specialty, Psychosis, QH426-470, Article, Cohort Studies, Risk Factors, Genetics, medicine, Humans, Risk factor, Genetics (clinical), Framingham Risk Score, business.industry, Patient Acuity, Prognosis, medicine.disease, Treatment Outcome, Clinical research, Psychotic Disorders, Schizophrenia, Cohort, Female, Polygenic risk score, business, Psychopathology
Abstract: Understanding and improving the outcomes of psychosis remains a major challenge for clinical research. Obstetric complications (OCs) as a risk factor for schizophrenia (SZ) have been investigated as a potential predictor of outcomes in relation to illness severity and poorer treatment outcome, but there are less reports on first episode psychosis (FEP) patients. We test whether OCs, collected in a cohort of FEP patients, can predict illness course and psychopathology severity after 2 years from the onset. Moreover, we explore whether the SZ-polygenic risk score (PRS) would predict the illness course and whether the interaction between OCS and PRS shows a significant effect. A cohort of 264 FEP patients were assessed with standardized instruments. OCs were recorded using the Lewis–Murray scale in interviews with the patients’ mothers: 30% of them reported at least one OC. Patients with at least one OC were more likely to have a non-remitting course of illness compared to those without OCs (35.3% vs. 16.3%, p = 0.014). No association between SZ-PRS and course of illness nor evidence for a gene–environment interaction was found. In our sample, poor short-term outcomes were associated with OCs, while SZ-PRS was not a prognostic indicator of poor outcomes.
Published: 2021
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34. Treated Incidence of Psychotic Disorders in the Multinational EU-GEI Study

Author: Hannah E. Jongsma, Charlotte Gayer-Anderson, Antonio Lasalvia, Diego Quattrone, Alice Mulè, Andrei Szöke, Jean-Paul Selten, Caitlin Turner, Celso Arango, Ilaria Tarricone, Domenico Berardi, Andrea Tortelli, Pierre-Michel Llorca, Lieuwe de Haan, Julio Bobes, Miguel Bernardo, Julio Sanjuán, José Luis Santos, Manuel Arrojo, Cristina Marta Del-Ben, Paulo Rossi Menezes, Robin M. Murray, Bart P. Rutten, Peter B. Jones, Jim van Os, Craig Morgan, James B. Kirkbride, Ulrich Reininghaus, Marta Di Forti, Kathryn Hubbard, Stephanie Beards, Simona A. Stilo, Giada Tripoli, Mara Parellada, Pedro Cuadrado, José Juan Rodríguez Solano, Angel Carracedo, Enrique García Bernardo, Laura Roldán, Gonzalo López, Bibiana Cabrera, Esther Lorente-Rovira, Paz Garcia-Portilla, Javier Costas, Estela Jiménez-López, Mario Matteis, Marta Rapado, Emiliano González, Covadonga Martínez, Emilio Sánchez, Mª Soledad Olmeda, Nathalie Franke, Eva Velthorst, Fabian Termorshuizen, Daniella van Dam, Elsje van der Ven, Elles Messchaart, Marion Leboyer, Franck Schürhoff, Jamain, Flora Frijda, Grégoire Baudin, Aziz Ferchiou, Baptiste Pignon, Jean-Romain Richard, Thomas Charpeaud, Anne-Marie Tronche, Daniele La Barbera, Caterina La Cascia, Giovanna Marrazzo, Lucia Sideli, Crocettarachele Sartorio, Laura Ferraro, Fabio Seminerio, Camila Marcelino Loureiro, Rosana Shuhama, Mirella Ruggeri, Sarah Tosato, Chiara Bonetto, Doriana Cristofalo, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience, APH - Mental Health, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Adult Psychiatry, Jongsma, Hannah [0000-0001-6346-5903], Jones, Peter [0000-0002-0387-880X], Apollo - University of Cambridge Repository, Hannah E. Jongsma, Charlotte Gayer-Anderson, Antonio Lasalvia, Diego Quattrone, Alice Mulè, Andrei Szöke, Jean-Paul Selten, Caitlin Turner, Celso Arango, Ilaria Tarricone, Domenico Berardi, Andrea Tortelli, Pierre-Michel Llorca, Lieuwe de Haan, Julio Bobes, Miguel Bernardo, Julio Sanjuán, José Luis Santos, Manuel Arrojo, Cristina Marta Del-Ben, Paulo Rossi Menezes,Robin M. Murray, Bart P. Rutten, Peter B. Jones, Jim van Os, Craig Morgan, James B. Kirkbride, Ulrich Reininghaus, Marta Di Forti, Kathryn Hubbard, Stephanie Beards, Simona A. Stilo, Giada Tripoli, Mara Parellada, Pedro Cuadrado, José Juan Rodríguez Solano, Angel Carracedo, Enrique García Bernardo, Laura Roldán, Gonzalo López, Bibiana Cabrera, Esther Lorente-Rovira, Paz Garcia-Portilla, Javier Costas, Estela Jiménez-López, Mario Matteis, Marta Rapado, Emiliano González, Covadonga Martínez, Emilio Sánchez, Mª Soledad Olmeda, Nathalie Franke, Eva Velthorst, Fabian Termorshuizen, Daniella van Dam, Elsje van der Ven, Elles Messchaart, Marion Leboyer, Franck Schürhoff, Jamain, Flora Frijda, Grégoire Baudin, Aziz Ferchiou, Baptiste Pignon, Jean-Romain Richard, Thomas Charpeaud, Anne-Marie Tronche, Daniele La Barbera, Caterina La Cascia, Giovanna Marrazzo, Lucia Sideli, Crocettarachele Sartorio, Laura Ferraro, Fabio Seminerio, Camila Marcelino Loureiro, Rosana Shuhama, Mirella Ruggeri, Sarah Tosato, Chiara Bonetto, Doriana Cristofalo, Hannah E. Jongsma, Charlotte Gayer-Anderson, Antonio Lasalvia, Diego Quattrone, Alice Mulè, Andrei Szöke, Jean-Paul Selten, Caitlin Turner, Celso Arango, Ilaria Tarricone, Domenico Berardi, Andrea Tortelli, Pierre-Michel Llorca, Lieuwe de Haan, Julio Bobe, Miguel Bernardo, Julio Sanjuán, José Luis Santo, Manuel Arrojo, Cristina Marta Del-Ben, Paulo Rossi Meneze, Robin M. Murray, Bart P. Rutten, Peter B. Jone, Jim van O, Craig Morgan, James B. Kirkbride, Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Dept. of Psychiatry, Adolescent Unit, Hospital General Universitario Gregorio Marañón, 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), iThemba LABS [National Research Foundation], National Research Foundation [South Africa] (NRF), Institute of Human Genetics, Rheinische Friedrich-Wilhelms-Universität Bonn, and iThemba Laboratory for Accelerator Based Science
Subjects: Male, 2.3 Psychological, social and economic factors, SYMPTOMS, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, environmental risk factors, Catchment Area, Health, Risk Factors, SCHIZOPHRENIA, DEPRIVATION, ComputingMilieux_MISCELLANEOUS, health care economics and organizations, Minority Groups, 44 Human Society, Original Investigation, Netherlands, 2 Aetiology, OUTCOMES, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, psychotic disorders, international multisite incidence study, EU-GEI Study, Incidence, Age Factors, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Mental Health, England, Italy, Psychiatry and Mental Health, 4206 Public Health, population characteristics, Female, France, geographic locations, Brazil, Adult, Cross-Cultural Comparison, URBANICITY, education, AGE, Sex Factors, parasitic diseases, Humans, 1ST-EPISODE PSYCHOSIS, RATES, NOTTINGHAM, METAANALYSIS, Publishing, [SCCO.NEUR]Cognitive science/Neuroscience, Prevention, 42 Health Sciences, Psychotic Disorders, Spain, Gene-Environment Interaction
Abstract: Importance: Psychotic disorders contribute significantly to the global disease burden, yet the latest international incidence study of psychotic disorders was conducted in the 1980s. Objectives: To estimate the incidence of psychotic disorders using comparable methods across 17 catchment areas in 6 countries and to examine the variance between catchment areas by putative environmental risk factors. Design, Setting, and Participants: An international multisite incidence study (the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions) was conducted from May 1, 2010, to April 1, 2015, among 2774 individuals from England (2 catchment areas), France (3 catchment areas), Italy (3 catchment areas), the Netherlands (2 catchment areas), Spain (6 catchment areas), and Brazil (1 catchment area) with a first episode of nonorganic psychotic disorders (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] codes F20-F33) confirmed by the Operational Criteria Checklist. Denominator populations were estimated using official national statistics. Exposures: Age, sex, and racial/ethnic minority status were treated as a priori confounders. Latitude, population density, percentage unemployment, owner-occupied housing, and single-person households were treated as catchment area-level exposures. Main Outcomes and Measures: Incidence of nonorganic psychotic disorders (ICD-10 codes F20-F33), nonaffective psychoses (ICD-10 codes F20-F29), and affective psychoses (ICD-10 codes F30-F33) confirmed by the Operational Criteria Checklist. Results: A total of 2774 patients (1196 women and 1578 men; median age, 30.5 years [interquartile range, 23.0-41.0 years]) with incident cases of psychotic disorders were identified during 12.9 million person-years at risk (crude incidence, 21.4 per 100 000 person-years; 95% CI, 19.4-23.4 per 100 000 person-years). A total of 2183 patients (78.7%) had nonaffective psychotic disorders. After direct standardization for age, sex, and racial/ethnic minority status, an 8-fold variation was seen in the incidence of all psychotic disorders, from 6.0 (95% CI, 3.5-8.6) per 100 000 person-years in Santiago, Spain, to 46.1 (95% CI, 37.3-55.0) per 100 000 person-years in Paris, France. Rates were elevated in racial/ethnic minority groups (incidence rate ratio, 1.6; 95% CI, 1.5-1.7), were highest for men 18 to 24 years of age, and were lower in catchment areas with more owner-occupied homes (incidence rate ratio, 0.8; 95% CI, 0.7-0.8). Similar patterns were observed for nonaffective psychoses; a lower incidence of affective psychoses was associated with higher area-level unemployment (incidence rate ratio, 0.3; 95% CI, 0.2-0.5). Conclusions and Relevance: This study confirmed marked heterogeneity in risk for psychotic disorders by person and place, including higher rates in younger men, racial/ethnic minorities, and areas characterized by a lower percentage of owner-occupied houses., The European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) Project is funded by grant agreement HEALTH-F2-2010-241909 (Project EU-GEI) from the European Community’s Seventh Framework Programme. The Brazilian study was funded by grant 2012/0417-0 from the São Paulo Research Foundation. Dr Kirkbride is funded by the Wellcome Trust and grant 101272/Z/13/Z from the Royal Society. Ms Jongsma and Dr Jones are funded by the National Institute of Health Research Collaboration of Leadership in Applied Health Research and Care East of England.
Published: 2018
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35. Epigenetics and gene expression profile in first-episode psychosis: The role of childhood trauma

Author: S. Tomassi and Sarah Tosato
Subjects: Epigenomics, Psychosis, Cognitive Neuroscience, Bioinformatics, Epigenesis, Genetic, 03 medical and health sciences, Behavioral Neuroscience, DISC1, 0302 clinical medicine, microRNA, Gene expression, medicine, Humans, Child Abuse, Epigenetics, Child, Serotonin Plasma Membrane Transport Proteins, biology, Brain-Derived Neurotrophic Factor, Epigenome, DNA Methylation, medicine.disease, 030227 psychiatry, Neuropsychology and Physiological Psychology, Psychotic Disorders, DNA methylation, biology.protein, Cancer research, Gene-Environment Interaction, FKBP5, 030217 neurology & neurosurgery
Abstract: Childhood Trauma (CT) mediation of the epigenome and its impact on gene expression profile could provide a mechanism for the gene-environment interaction underling psychosis. We reviewed the evidence concerning epigenetic and gene expression modifications associated with CT in both First-Episode Psychosis (FEP) and healthy subjects. In order to explore the relative role of psychosis itself in determining these modifications, evidence about FEP and epigenetics/gene expression was also summarized. We performed a systematic search on PubMed, last updated in December 2016. Out of 2966 potentially relevant records, only 41 studies were included. CT resulted associated: in FEP subjects, with global DNA hypo-methylation and reduced BDNF gene-expression; in healthy subjects, with hyper-methylation of SLC6A4, NR3C1, KITLG, and OXTR; hypo-methylation of FKBP5, IL-6, and BDNF; increased IL1B, IL8, and PTGS gene expression; and decreased SLC6A4 gene expression. FEP showed global DNA hypo-methylation; increased methylation and reduced gene expression of GCH1; hyper-expression of MPB, NDEL1, AKT1, and DICER1; and hypo-expression of DROSHA, COMT, and DISC1 in comparison with healthy controls.
Published: 2017
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36. Aggression and violence towards healthcare workers in a psychiatric service in Italy. A retrospective questionnaire-based survey

Author: Sarah Tosato, Andreas Conca, Chiara Bonetto, S. Moser, J.V. Bizzarri, and Daria Piacentino
Subjects: medicine.medical_specialty, Health professionals, business.industry, Aggression, Significant difference, Test (assessment), Questionnaire based survey, Psychiatry and Mental health, Rehabilitation facility, Health care, Medicine, medicine.symptom, business, Psychiatry
Abstract: IntroductionViolence at work is a major concern in healthcare services. Prevention programs have been implemented, albeit being scarce in Italy.Objectives or AimsThe Bolzano psychiatric department adopted a de-escalation model developed by the Institut-für-Professionelles-Deeskalations-Management (ProDeMa®). It includes evaluation, prevention, and practical training aimed at preventing/reducing patients’ aggressive behavior toward healthcare workers.MethodsIn 2015, health professionals were interviewed by using a ProDeMa® 11-item questionnaire that assessed the type and frequency of endured patients’ aggressive behavior, as well as the conditions capable of producing or preventing it. One-way ANOVA with Tukey post-hoc test was used for comparisons.ResultsA total of 165/211 (78%) surveyed workers (mean age ± DE = 44.9 ± 7.7; females = 64.6%) completed the questionnaire, of whom 21% employed at the inpatients unit (INP), 37% at the outpatients unit (OUTP), 42% at the rehabilitation facility (REHAB). The one-year number of verbal aggressions (VA) was 9766, with INP (mean ± SD = 15.2 ± 29.6) vs. OUTP (mean ± SD = 6.2 ± 30.6) vs. REHAB (mean ± SD = 8.4 ± 26.1). The one-year number of physical aggressions (PA) was 1502, with INP (mean ± SD = 3.3 ± 12.2) vs. OUTP (mean ± SD = 0.1 ± 0.5) vs. REHAB (mean ± SD = 0.1 ± 0.7). The one-year number of injuries (IN) was 200, with INP (mean ± SD = 0.5 ± 1.9) vs. OUTP (mean ± SD = 0.1 ± 0.5) vs. REHAB (mean ± SD = 0.1 ± 0.2). ANOVA showed significant differences in terms of mean verbal/physical aggression and injuries among the three workplaces (P-values = 0.000), with post-hoc Tukey test showing a significant difference of INP vs. REHAB and OUTP. The most frequent risk factors identified by the staff for precipitating aggression included rigid rules (15.1%) and inadequate communication (9.1%).ConclusionsThe three types of violence are common in all facilities of our Department.Disclosure of interestThe authors have not supplied their declaration of competing interest.
Published: 2017
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37. Dietary habits and physical activity in first-episode psychosis patients treated in community services. Effect on early anthropometric and cardio-metabolic alterations

Author: Sarah Bissoli, Mirella Ruggeri, Lorenza Lazzarotto, Mariaelena Bertani, Elena Saugo, Francesco Gardellin, Enrico Ceccato, Sara Poli, Doriana Cristofalo, Chiara Bonetto, Michele Pavanati, Sarah Tosato, and Antonio Lasalvia
Subjects: medicine.medical_specialty, Psychosis, First episode psychosis, Mediterranean diet, medicine.medical_treatment, Context (language use), 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Dietary habits, Metabolic patterns, Physical activity, Internal medicine, Heart rate, medicine, Humans, Antipsychotic, Exercise, Biological Psychiatry, Retrospective Studies, business.industry, Cholesterol, Feeding Behavior, Anthropometry, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Blood pressure, chemistry, Psychotic Disorders, business, 030217 neurology & neurosurgery, Social Welfare, Follow-Up Studies
Abstract: People with psychosis often develop metabolic and cardiovascular disorders, due to several factors including unhealthy lifestyle and antipsychotic treatment. This study aims to evaluate in a sample of first episode psychosis (FEP) patients lifestyle factors, with a specific emphasis on dietary habits and physical activity, and cardio-metabolic and anthropometric profile at illness onset and at 9 months. Moreover, this study aims to evaluate the impact of lifestyle factors on short term changes in cardio-metabolic and anthropometric profile. A 9-month follow-up study was conducted on a sample of 96 FEP patients recruited within the context of the GET UP program. Standardised assessments of dietary habits (EPIC) and physical activity (IPAQ) were retrospectively performed at 9 months; cardiovascular measures (blood pressure, heart rate), metabolic parameters (glucose, cholesterol, triglycerides), BMI and antipsychotic treatment were assessed at illness onset and at 9 months. We found that most FEP patients (60%) displayed poor dietary habits, as defined in terms of adherence to the Mediterranean diet. A significant increase for both BMI and cholesterol levels was found in the overall sample over 9 months. However, when considering the effect of lifestyle factors, BMI and total cholesterol were specifically raised in patients with low adherence to Mediterranean diet. The association with antipsychotic medication was found for SGA only, with a significant increase in both BMI and total cholesterol overtime. Our findings confirm the need to implement specific and early strategies to promote healthy lifestyle in people with FEP, since metabolic alterations occur within the first months of treatment.
Published: 2020

38. Pre-training inter-rater reliability of clinical instruments in an international psychosis research project

Author: Steven Berendsen, Pim Kapitein, Frederike Schirmbeck, Mirjam J. van Tricht, Philip McGuire, Craig Morgan, Charlotte Gayer-Anderson, Matthew J. Kempton, Lucia Valmaggia, Diego Quattrone, Marta di Forti, Mark van der Gaag, James B. Kirkbride, Hannah E. Jongsma, Peter B. Jones, Maria Parellada, Celso Arango, Manuel Arrojo, Miguel Bernardo, Julio Sanjuán, José Luis Santos, Andrei Szöke, Andrea Tortelli, Pierre-Michel Llorca, Ilaria Tarricone, Giada Tripoli, Laura Ferraro, Caterina La Cascia, Antonio Lasalvia, Sarah Tosato, Paulo Rossi Menezes, Cristina Marta Del-Ben, Barnaby Nelson, Anita Riecher-Rössler, Rodrigo Bressan, Neus Barrantes-Vidal, Marie-Odile Krebs, Merete Nordentoft, Stephan Ruhrmann, Gabriele Sachs, Bart P.F. Rutten, Jim van Os, Eva Velthorst, Lieuwe de Haan, Maria Calem, Stefania Tognin, Gemma Modinos, Sara Pisani, Tamar C. Kraan, Daniella S. van Dam, Nadine Burger, Patrick McGorry, G. Paul Amminger, Athena Politis, Joanne Goodall, Stefan Borgwardt, Erich Studerus, Ary Gadelha, Elisa Brietzke, Graccielle Asevedo, Elson Asevedo, Andre Zugman, Tecelli Domínguez-Martínez, Manel Monsonet, Lidia Hinojosa, Paula Cristóbal-Narváez, Anna Racioppi, Thomas R. Kwapil, Mathilde Kazes, Claire Daban, Julie Bourgin, Olivier Gay, Célia Mam-Lam-Fook, Dorte Nordholm, Lasse Randers, Kristine Krakauer, Louise Birkedal Glenthøj, Birte Glenthøj, Dominika Gebhard, Julia Arnhold, Joachim Klosterkötter, Iris Lasser, Bernadette Winklbaur, Philippe A. Delespaul, Graduate School, Adult Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Berendsen S., Kapitein P., Schirmbeck F., van Tricht M.J., McGuire P., Morgan C., Gayer-Anderson C., Kempton M.J., Valmaggia L., Quattrone D., di Forti M., van der Gaag M., Kirkbride J.B., Jongsma H.E., Jones P.B., Parellada M., Arango C., Arrojo M., Bernardo M., Sanjuan J., Santos J.L., Szoke A., Tortelli A., Llorca P.-M., Tarricone I., Tripoli G., Ferraro L., La Cascia C., Lasalvia A., Tosato S., Menezes P.R., Del-Ben C.M., Nelson B., Riecher-Rossler A., Bressan R., Barrantes-Vidal N., Krebs M.-O., Nordentoft M., Ruhrmann S., Sachs G., Rutten B.P.F., van Os J., Velthorst E., de Haan L., Calem M., Tognin S., Modinos G., Pisani S., Kraan T.C., van Dam D.S., Burger N., McGorry P., Amminger G.P., Politis A., Goodall J., Borgwardt S., Studerus E., Gadelha A., Brietzke E., Asevedo G., Asevedo E., Zugman A., Dominguez-Martinez T., Monsonet M., Hinojosa L., Cristobal-Narvaez P., Racioppi A., Kwapil T.R., Kazes M., Daban C., Bourgin J., Gay O., Mam-Lam-Fook C., Nordholm D., Randers L., Krakauer K., Glenthoj L.B., Glenthoj B., Gebhard D., Arnhold J., Klosterkotter J., Lasser I., Winklbaur B., Delespaul P.A., RS: MHeNs - R3 - Neuroscience, Psychiatrie & Neuropsychologie, MUMC+: MA Psychiatrie (3), RS: MHeNs - R2 - Mental Health, and MUMC+: Hersen en Zenuw Centrum (3)
Subjects: Research design, Psychosis, INFORMATION, IMPACT, Applied psychology, MEDLINE, Assessor selection, Pre-training inter-rater reliability, Psychosis instruments, 03 medical and health sciences, 0302 clinical medicine, Medicine, Humans, Biological Psychiatry, ComputingMilieux_MISCELLANEOUS, Observer Variation, REPRODUTIBILIDADE DE RESULTADOS, business.industry, Pre-training inter-rater reliability, Reproducibility of Results, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Inter-rater reliability, Assessor selection, TRIALS, Psychotic Disorders, Research Design, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MEASUREMENT ERROR, business, Observer variation, 030217 neurology & neurosurgery, Psychosis instruments
Abstract: International audience
Published: 2019
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39. Schizophrenia polygenic risk score and cannabis use modify psychosis expression in first episode psychosis patients and population controls

Author: Peter B. Jones, Robin M. Murray, Jose Luis Santos, Di Forti M, Ilaria Tarricone, Tom P. Freeman, Bart P. F. Rutten, Sarah Tosato, Giada Tripoli, Craig Morgan, Elena Bonora, James B. Kirkbride, Cathryn M. Lewis, Celso Arango, Pak C. Sham, Charlotte Gayer-Anderson, Julio Bobes, Hannah E. Jongsma, Paolo Marino, Ulrich Reininghaus, Rodriguez, Alastair G. Cardno, van os J, Eva Velthorst, Evangelos Vassos, Michael T. Lynskey, La Barbera D, Miguel Bernardo, Paulo Rossi Menezes, Andrea Tortelli, Laura Ferraro, de Haan L, Pierre-Michel Llorca, Alexander Richards, Del Ben Cm, Andrei Szöke, Antonio Lasalvia, Diego Quattrone, La Cascia C, Julio Sanjuán, and M O'Donovan
Subjects: education.field_of_study, Psychosis, business.industry, Population, Cannabis use, medicine.disease, 030227 psychiatry, 03 medical and health sciences, 0302 clinical medicine, Environmental risk, Schizophrenia, First episode psychosis, Medicine, Polygenic risk score, In patient, business, education, 030217 neurology & neurosurgery, Clinical psychology
Abstract: BackgroundDiagnostic categories within the psychosis spectrum are widely used in clinical practice, however psychosis may occur on a continuum. Therefore, we explored whether the continuous distribution of psychotic symptoms across categories is a function of genetic as well as environmental risk factors, such as polygenic risk scores (PRSs) and cannabis use.MethodsAs part of the EU-GEI study, we genotyped first episode psychosis patients (FEP) and population controls, for whom transdiagnostic dimensions of psychotic symptoms or experiences were generated using item response bi-factor modelling. Linear regression was used, separately in patients and controls, to test the associations between these dimensions and schizophrenia (SZ) PRSs, as well as the combined effect of SZ-PRS and cannabis use on the positive symptom/experience dimensions.ResultsSZ-PRS was associated with negative (B=0.18; 95%CI 0.03 to 0.34) and positive (B=0.19; 95%CI 0.03 to 0.36) symptom dimensions in 617 FEP, and with all the psychotic experience dimensions in 979 controls. The putative effect of SZ-PRS on either symptom or experience dimensions was of a small magnitude. Cannabis use was additionally associated with the positive dimensions both in FEP (B=0.31; 95%CI 0.11 to 0.52) and in controls (B=0.26; 95%CI 0.06 to 0.46), independently from SZ-PRS.ConclusionsWe report two validators to the latent dimensional structure of psychosis. SZ risk variants and cannabis use independently map onto specific dimensions, contributing to variation across the psychosis continuum. Findings support the hypothesis that psychotic experiences have similar biological substrates as clinical disorders.
Published: 2019
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40. The independent and combined influence of schizophrenia polygenic risk score and heavy cannabis use on risk for psychotic disorder: A case-control analysis from the EUGEI study

Author: Manuel Arrojo, Alexander Richards, Jose Luis Santos, Del Ben Cm, Ilaria Tarricone, Wu-Choi B, Domenico Berardi, Laura Ferraro, Julio Sanjuán, M O'Donovan, Peter B. Jones, Andrei Szöke, Diego Quattrone, Julio Bobes, Evangelos Vassos, Rutten Bn, Giada Tripoli, James B. Kirkbride, Miguel Bernardo, Jean-Paul Selten, Pak C. Sham, Celso Arango, Eva Velthorst, Hannah E. Jongsma, Robin M. Murray, Michael T. Lynskey, Di Forti M, La Cascia C, de Haan L, Charlotte Gayer-Anderson, Rodriguez, Sarah Tosato, van os J, Cathryn M. Lewis, Tom P. Freeman, and Craig Morgan
Subjects: medicine.medical_specialty, biology, business.industry, Frequency of use, Cannabis use, biology.organism_classification, medicine.disease, 030227 psychiatry, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Schizophrenia, First episode psychosis, Case control analysis, Medicine, media_common.cataloged_instance, Polygenic risk score, Cannabis, European union, business, Psychiatry, 030217 neurology & neurosurgery, media_common
Abstract: Background: Some recent studies have challenged the direction of causality for the association between cannabis use and psychotic disorder, suggesting that cannabis use initiation is explained by common genetic variants associated with risk of schizophrenia. We used data from the European Union Gene-Environment Interaction consortium (EUGEI) case-control study to test for the independent and combined effect of heavy cannabis use, and of Schizophrenia Polygenic risk score (SZ PRS), on risk for psychotic disorder. Methods: Genome-wide data were obtained from 492 first episode psychosis patients (FEPp) and from 787 controls of European Ancestry, and used to generate SZ PRS from the summary results of an independent meta-analysis. Information on pattern of cannabis use was used to build a 7-level frequency-type composite cannabis use measure that we previously found was a strong predictor of psychotic disorder. Results: SZ PRS did not predict cannabis initiation (b=0.027; p=0.51) or how frequently controls (b=0.027; p=0.06) or FEPp (b=0.006; p=0.91) used it, or the type of cannabis they used (Controls: b = 0.032; p=0.31); FEPp: b= 0.005; p=0.89). The frequency-type composite cannabis use measure (OR=1.32; 95% CI 1.22-1.44) and SZ PRS (OR=2.29; 95%CI 1.71-3.05) showed independent effects from each other on the OR for psychotic disorder. Conclusion: SZ PRS does not predict an individual s propensity to try cannabis, frequency of use, or the potency of the cannabis used. Our findings provide the first evidence that SZ PRS and heavy cannabis use exert effects independent from each other on the risk for psychotic disorder.
Published: 2019
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41. Population-based identity-by-descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia

Author: Eleni Giannoulatou, Nancy Buccola, Tune Pers, Sarah TOSATO, Christos Pantelis, James Walters, Hon-Cheong So, Igor Nenadić, Joseph Buxbaum, Lili Milani, Miloš Milovančević, Naomi Wray, Joanne Knight, Nicholas Wood, Srihari Gopal, Silviu-Alin Bacanu, Colin Palmer, Inez Myin-Germeys, Francis Anthony O'Neill, Matthew A Brown, Sang Hong Lee, Robert Plomin, Peter Visscher, Tracey Petryshen, Preben Bo Mortensen, Thomas Folkmann Hansen, Esben Agerbo, Digby Quested, Jianjun Liu, Engilbert Sigurdsson, Sara Marsal, Céline Bellenguez, Robert Freedman, Panos Deloukas, Ditte Demontis, Donald Black, David Collier, Fritz Zimprich, Clement C Zai, Nakao IWATA, Elvira Bramon, Masashi Ikeda, Andrew McIntosh, Bryan Mowry, Patrik Magnusson, Janis Klovins, Srdjan Djurovic, Jim Van Os, Ulrich Schall, Jan Lubinski, Milica Pejovic Milovancevic, Kang Sim, Rodney Scott, Anders Børglum, Jennifer Moran, Denise Harold, Sergi Papiol, Bradley Webb, Elisabeth Stögmann, Davidson, Michael, Germeys, Inez, Harold, Denise, Connolly, Siobhan, Riley, Brien P, Kendler, Kenneth S, McCarthy, Shane E, McCombie, William R, Richards, Alex, Owen, Michael J, O'Donovan, Michael C, Walters, James, Donohoe, Gary, Gill, Michael, Corvin, Aiden, Morris, Derek W, Lee, SH, Schizophrenia Working Group of the Psychiatric Genomics Consortuim, Wellcome Trust Case Control Consortium, National Institutes of Health, Science Foundation Ireland, Wellcome Trust, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, and Adult Psychiatry
Subjects: Male, Genome-wide association study, WHOLE-GENOME ASSOCIATION, Identity by descent, 0302 clinical medicine, Risk Factors, Databases, Genetic, 2.1 Biological and endogenous factors, GWAS, Exome, Copy-number variation, Aetiology, Genetics (clinical), Exome sequencing, Genetics & Heredity, Psychiatry, Schizophrenia Working Group of the Psychiatric Genomics Consortium, 0303 health sciences, Chromosome Mapping, Middle Aged, Serious Mental Illness, 3. Good health, Psychiatry and Mental health, Mental Health, DISEASES, Female, BURDEN, Sequence Analysis, Life Sciences & Biomedicine, Adult, GENES, DNA Copy Number Variations, Genotype, DISORDERS, Clinical Sciences, Single-nucleotide polymorphism, Computational biology, Biology, IBD mapping, Article, Databases, 03 medical and health sciences, Cellular and Molecular Neuroscience, Genetic, Clinical Research, Exome Sequencing, rare variants, Genetics, Humans, Genetic Predisposition to Disease, AUTISM, Genome‐wide association studies (GWASs), 030304 developmental biology, Genetic association, Science & Technology, risk variants, Prevention, Wellcome Trust Case Control Consortium 2, Human Genome, Haplotype, Neurosciences, DNA, Sequence Analysis, DNA, Brain Disorders, Haplotypes, DE-NOVO MUTATIONS, Case-Control Studies, API, Schizophrenia, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Genome‐wide association studies (GWASs) are highly effective at identifying common risk variants for schizophrenia. Rare risk variants are also important contributors to schizophrenia etiology but, with the exception of large copy number variants, are difficult to detect with GWAS. Exome and genome sequencing, which have accelerated the study of rare variants, are expensive so alternative methods are needed to aid detection of rare variants. Here we re‐analyze an Irish schizophrenia GWAS dataset (n = 3,473) by performing identity‐by‐descent (IBD) mapping followed by exome sequencing of individuals identified as sharing risk haplotypes to search for rare risk variants in coding regions. We identified 45 rare haplotypes (>1 cM) that were significantly more common in cases than controls. By exome sequencing 105 haplotype carriers, we investigated these haplotypes for functional coding variants that could be tested for association in independent GWAS samples. We identified one rare missense variant in PCNT but did not find statistical support for an association with schizophrenia in a replication analysis. However, IBD mapping can prioritize both individual samples and genomic regions for follow‐up analysis but genome rather than exome sequencing may be more effective at detecting risk variants on rare haplotypes. National Institutes of Health, Grant/Award Numbers: R01‐MH041953, R01‐MH083094; Science Foundation Ireland, Grant/Award Numbers: 08/IN.1/B1916, 12/IP/1359, 12/IP/1670; Wellcome Trust, Grant/Award Number: 085475/B/08/Z peer-reviewed
Published: 2019
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42. Classification of first-episode psychosis in a large cohort of patients using support vector machine and multiple kernel learning techniques

Author: Giada Zoccatelli, Doriana Cristofalo, Franco Alessandrini, F Mazzi, Letizia Squarcina, Umberto Castellani, Paolo Santonastaso, Roberto Pozzi-Mucelli, Mirella Ruggeri, Francesca Pileggi, Chiara Bonetto, Marcella Bellani, Gianluca Rambaldelli, Sarah Tosato, Antonio Lasalvia, Nicola Dusi, Dario Lamonaca, Enrico Ceccato, Paolo Brambilla, and Cinzia Perlini
Subjects: Adult, Male, affective psychosis, cortical thickness, frontal, MRI, schizophrenia, temporal cortex, Support Vector Machine, Cognitive Neuroscience, Population, Machine Learning, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, Covariate, Statistics, Humans, Medicine, education, Cerebral Cortex, Temporal cortex, education.field_of_study, Multiple kernel learning, business.industry, Confounding, Pattern recognition, Magnetic Resonance Imaging, 030227 psychiatry, Support vector machine, Psychotic Disorders, Neurology, Kernel (statistics), Female, Artificial intelligence, Affective psychosis, Cortical thickness, Frontal, Schizophrenia, business, 030217 neurology & neurosurgery
Abstract: First episode psychosis (FEP) patients are of particular interest for neuroimaging investigations because of the absence of confounding effects due to medications and chronicity. Nonetheless, imaging data are prone to heterogeneity because for example of age, gender or parameter setting differences. With this work, we wanted to take into account possible nuisance effects of age and gender differences across dataset, not correcting the data as a pre-processing step, but including the effect of nuisance covariates in the classification phase. To this aim, we developed a method which, based on multiple kernel learning (MKL), exploits the effect of these confounding variables with a subject-depending kernel weighting procedure. We applied this method to a dataset of cortical thickness obtained from structural magnetic resonance images (MRI) of 127 FEP patients and 127 healthy controls, who underwent either a 3Tesla (T) or a 1.5T MRI acquisition. We obtained good accuracies, notably better than those obtained with standard SVM or MKL methods, up to more than 80% for frontal and temporal areas. To our best knowledge, this is the largest classification study in FEP population, showing that fronto-temporal cortical thickness can be used as a potential marker to classify patients with psychosis.
Published: 2017
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43. Psychiatric disorders

Author: Simona Tomassi, Ilaria Tarricone, and Sarah Tosato
Subjects: gender, psychiatric disorders, depression, psychosis, peripartum psychiatry, psychiatric disorders, peripartum psychiatry, depression, gender, psychosis
Published: 2019

44. Dimensional structure of first episode psychosis

Author: Carlo Marchesi, Katia De Santi, Carla Comacchio, Emanuela Leuci, Elena Bettini, Massimo Cellini, Paola Rucci, Chiara Bonetto, Jacopo Lenzi, Antonio Lasalvia, Maurizio Miceli, Doriana Cristofalo, Paolo Santonastaso, Giovanni de Girolamo, Angelo Fioritti, Daniela Ghigi, Paolo Ossola, Laura Iozzino, Silvio Scarone, Anna Meneghelli, Matteo Tonna, Sarah Tosato, Francesca Pileggi, Angela Veronese, Stefano Torresani, Armando D'Agostino, Mirella Ruggeri, Tonna M., Ossola P., Marchesi C., Bettini E., Lasalvia A., Bonetto C., Lenzi J., Rucci P., Iozzino L., Cellini M., Comacchio C., Cristofalo D., D'Agostino A., de Girolamo G., De Santi K., Ghigi D., Leuci E., Miceli M., Meneghelli A., Pileggi F., Scarone S., Santonastaso P., Torresani S., Tosato S., Veronese A., Fioritti A., and Ruggeri M.
Subjects: Adult, Male, affective symptoms, dimension, first episode psychosis, negative symptoms, positive symptoms, Psychosis, Psychological intervention, Delusions, law.invention, Young Adult, Randomized controlled trial, Rating scale, law, medicine, Cluster Analysis, Humans, negative symptom, Biological Psychiatry, Depression (differential diagnoses), Randomized Controlled Trials as Topic, Psychiatric Status Rating Scales, Positive and Negative Syndrome Scale, Depression, business.industry, affective symptom, medicine.disease, Diagnostic and Statistical Manual of Mental Disorders, Psychiatry and Mental health, Italy, Psychotic Disorders, first episode psychosi, Female, Pshychiatric Mental Health, medicine.symptom, business, Mania, Clinical psychology, Psychopathology
Abstract: Aim Current diagnostic systems, DSM-5 and ICD-10, still adopt a categorical approach to classify psychotic disorders. The present study was aimed at investigating the structure of psychotic symptomatology in both affective and non-affective psychosis from a dimensional approach. Methods Participants with a first episode psychosis (FEP) were recruited from a cluster-randomized controlled trial (GET-UP PIANO TRIAL), offered to all Community Mental Health Centres (CMHCs) located across two northern Italian regions. After clinical stabilization, patients were assessed with a comprehensive set of psychopathological measures including the Positive and Negative Syndrome Scale, the Hamilton Depression Rating Scale and the Bech-Rafaelsen Mania Rating Scale. A two-step cluster analysis was performed. Results Overall, 257 FEP patients (male, n = 171, 66.5%; mean age = 24.96 ± 4.56) were included in the study. The cluster analysis revealed a robust four-cluster solution: delusional-persecutory (n = 82; 31.9%), depressed (n = 95; 37%), excited (n = 26; 10.1%) and negative-disorganized (n = 54; 21%), thus suggesting a quadripartite structure with both affective and non-affective dimensions. Among non-affective dimensions, negative and disorganization symptoms constituted a unique construct apart from positive symptoms. Conclusions Symptom dimensions may represent a useful tool for dissecting the indistinct and non-specific psychopathology of FEP in order to better target specific interventions.
Published: 2019

45. Pathways to care, DUP, and types of interventions over 5 years following psychosis onset: findings from a naturalistic study conducted in routine generalist mental health services

Author: Katia De Santi, Antonio Lasalvia, Doriana Cristofalo, Luana Ramon, Carla Comacchio, Elisabetta Miglietta, Chiara Bonetto, Mirella Ruggeri, Sarah Tosato, Gioia Zanatta, Carla Cremonese, and S. Petterlini
Subjects: Adult, Male, Mental Health Services, Psychosis, medicine.medical_specialty, Health (social science), Time Factors, Social Psychology, Adolescent, Epidemiology, Psychological interventions, Patterns of care, Psychological intervention, Context (language use), Time-to-Treatment, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Naturalistic observation, Outcome Assessment, Health Care, medicine, Duration of untreated psychosis (DUP), Humans, 030212 general & internal medicine, Practice Patterns, Physicians', Psychiatry, Referral and Consultation, business.industry, Pathways to care, Incidence, medicine.disease, First-episode psychosis (FEP), Mental health, 030227 psychiatry, Psychiatry and Mental health, Italy, Psychotic Disorders, Cohort, dup, Critical Pathways, Female, business
Abstract: To describe pathways to care, duration of untreated psychosis (DUP), and types of interventions provided to first-episode psychosis (FEP) patients by routine Italian mental health services over 5 years since the first service contact. Naturalistic study conducted in Veneto, within the context of the Psychosis Incident Cohort Outcome Study (PICOS). A comprehensive set of measures was used, including schedules designed to collect information on referrals to psychiatric services and on psychological and pharmacological treatments at 1, 2, and 5 years since first service contact. Overall, 397 patients were assessed. Most engaged with services with the help of family members (47.4%) and through emergency routes (60.3%). Those referred by clinicians were more likely to access care in a non-emergency way. Mean DUP was 5.62 months (SD 11.8) and longer DUP was associated with poorer functioning at 2 and 5 years. Interventions provided over 5 years were mainly constituted by antipsychotic medications (95.4% at 1 year; 85.8% at 2 years; 80.6% at 5 years), whereas a lower percentage (69.1% at 1 year; 61.5% at 2 years; 44.9% at 5 years) also received some forms of psychological interventions, mainly consisting of unspecific support sessions. Other structured interventions, such as CBT or family interventions, were seldom provided at each time-point. Mental health services in Veneto seem effective in engaging FEP patients within a short time since illness onset. However, type of care provided does not meet quality standards recommended by treatment guidelines, especially regarding psychological interventions.
Published: 2018

46. Cross-Cultural Issues

Author: Albert Diefenbacher, Adil Qureshi, Sarah Tosato, Nasim Chaudhry, Iris T Graef-Calliess, Mauro Braca, Ilaria Tarricone, Dinesh Bhugra, Silvia Ferrari, Nusrat Husain, Ronald Burian, Marianne Kastrup, Meryam Schouler-Ocak, and Domenico Berardi
Subjects: Ethnic group, Service provider, medicine.disease, computer.software_genre, Mental health, Nursing, Good clinical practice, medicine, Cross-cultural, Psychology, Somatization, computer, Cultural competence, Interpreter
Abstract: Migrants and ethnic minorities are at higher risk to develop mental disorders compared to native population. Culture has an important impact on the symptom presentation, diagnostic process and treatment strategies in all populations. Cultural competence represents good clinical practice and can be defined as a two-way learning encounter where clinician acknowledges the patient’s culture as well as his own cultural values and prejudices. Cultural competent response to the mental health care requires knowledge, skills and attitudes. Both individual and organizational cultural competences are needed to improve the effectiveness of psychiatric treatment. In this chapter, we revised the WPA Guidance on Mental Health and Mental Health Care for Migrants and the EPA Guidance on Mental Health Care for Migrants and list a series of recommendations for policy-makers, service providers and clinicians. Cultural competent experiences in the treatment of somatization and other psychiatric disorders across several countries in Europe are also presented.
Published: 2018
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47. The impact of gender and childhood abuse on age of psychosis onset, psychopathology and needs for care in psychosis patients

Author: Elisabetta Miglietta, Carla Comacchio, Enrico Semrov, Chiara Bonetto, Giovanni Neri, Riccardo Lo Parrino, Sarah Tosato, Antonio Preti, Doriana Cristofalo, Mirella Ruggeri, Antonio Lasalvia, Luca Mesiano, Katia De Santi, Karin Furlato, Giovanni de Girolamo, and Louise M. Howard
Subjects: Adult, Male, First episode psychosis, medicine.medical_specialty, Psychosis, History of childhood, Context (language use), Childhood trauma, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Sex Factors, Adverse Childhood Experiences, medicine, Prevalence, Humans, Age of Onset, Psychiatry, Physical abuse, Biological Psychiatry, Health Services Needs and Demand, business.industry, Childhood abuse, Sexual abuse, Adult Survivors of Child Abuse, Age Factors, Gender, Middle Aged, FEP, medicine.disease, Mental health, 030227 psychiatry, Psychiatry and Mental health, Psychotic Disorders, Female, Age of onset, business, 030217 neurology & neurosurgery, Psychopathology
Abstract: Gender is associated with several features of psychotic disorders, including age of illness onset, symptomatology, a higher prevalence of history of childhood sexual abuse (CSA) and needs for care. Childhood sexual abuse is associated with adverse mental health consequences but as there is a gender difference in stress reactivity, there may be a differential impact of CSA on psychopathology, age of psychosis onset and needs for care in First Episode Psychosis (FEP) patients. We hypothesized that a history of abuse would be associated with lowering of age of onset, increased symptomatology and more unmet needs in women but not men. A total of 444 FEP patients have been recruited within the context of the GET UP trial. Symptomatology has been assessed using the PANSS scale, needs for care with the CAN scale and childhood abuse with the CECA-Q scale. Childhood sexual abuse was more frequent among female patients [22.6% in women vs 11.6% in men (OR = 0.45, p 0.01)], whereas there was no gender difference in the prevalence of childhood physical abuse (29.0% in women vs 31.7% in men). Childhood abuse was associated with higher levels of negative symptoms in both men and women, with a reduced age of onset in women only and little increase in needs for care in both men and women. Our results seem to suggest that childhood sexual abuse in female FEP patients may be linked to a more severe form of psychosis whose presentation is characterized by earlier age of onset and higher levels of negative symptoms and we can also speculate that gender-specific protective factors in women, but not in men, may be outweighed by the consequences of childhood abuse.
Published: 2018
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48. A correction for sample overlap in genome-wide association studies in a polygenic pleiotropy-informed framework

Author: Nicholas Schork, Peter Schofield, Nancy Buccola, Paola Giusti-Rodríguez, Verena Zuber, Sarah TOSATO, Detelina Grozeva, Christos Pantelis, James Walters, Joseph Buxbaum, Miloš Milovančević, Niklas Långström, Gunnar Morken, Julia Newton-Bishop, Pamela Mahon, Inez Myin-Germeys, Sang Hong Lee, Peter Visscher, Lisa Jones, Michael O'Donovan, Bettina Kulle Andreassen, Francis McMahon, Tracey Petryshen, Thomas Folkmann Hansen, Esben Agerbo, Benedicto Crespo-Facorro, Jianjun Liu, Engilbert Sigurdsson, William Coryell, Arnoldo Frigessi, Robert Freedman, Soumya Raychaudhuri, Donald Black, Allan Young, Fritz Zimprich, Clement C Zai, Stéphane Jamain, Nakao IWATA, Pierandrea Muglia, Elvira Bramon, Masashi Ikeda, Andrew McIntosh, Bryan Mowry, Janis Klovins, Paul Tooney, Ulrich Schall, Jan Lubinski, Milica Pejovic Milovancevic, Kang Sim, Rodney Scott, Jennifer Moran, Bradley Webb, Elisabeth Stögmann, Germeys, Inez, LeBlanc, Marissa [0000-0003-2148-2814], Apollo - University of Cambridge Repository, Le Blanc, Marissa, Zuber, Verena, Thompson, Wesley K, Andreassen, Ole A, Frigessi, Arnoldo, Andreassen, Bettina Kulle, Lee, Sang Hong, Schizophrenia and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Adult Psychiatry, and Universidad de Cantabria
Subjects: 0301 basic medicine, False discovery rate, Spurious correlation, Genome-wide association study, VARIANTS, Covariate-modulated false discovery rate, Medical and Health Sciences, Correlation, Pleiotropy, Joint probability distribution, Statistics, Genetics & Heredity, Methodology Article, 11 Medical And Health Sciences, Single Nucleotide, Biological Sciences, Schizophrenia and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium, 3. Good health, Phenotype, Mental Health, Cross-phenotype association, Data integration, Life Sciences & Biomedicine, TRAITS, Biotechnology, STRATEGIES, lcsh:QH426-470, Genotype, Bioinformatics, lcsh:Biotechnology, Sample (statistics), Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, lcsh:TP248.13-248.65, Information and Computing Sciences, Genetics, Humans, Computer Simulation, Polymorphism, METAANALYSIS, Statistical hypothesis testing, Meta-analysis with shared subjects, 08 Information And Computing Sciences, Science & Technology, Human Genome, nutritional and metabolic diseases, 06 Biological Sciences, Brain Disorders, lcsh:Genetics, 030104 developmental biology, Biotechnology & Applied Microbiology, Case-Control Studies, Genome-Wide Association Study
Abstract: BACKGROUND: There is considerable evidence that many complex traits have a partially shared genetic basis, termed pleiotropy. It is therefore useful to consider integrating genome-wide association study (GWAS) data across several traits, usually at the summary statistic level. A major practical challenge arises when these GWAS have overlapping subjects. This is particularly an issue when estimating pleiotropy using methods that condition the significance of one trait on the signficance of a second, such as the covariate-modulated false discovery rate (cmfdr). RESULTS: We propose a method for correcting for sample overlap at the summary statistic level. We quantify the expected amount of spurious correlation between the summary statistics from two GWAS due to sample overlap, and use this estimated correlation in a simple linear correction that adjusts the joint distribution of test statistics from the two GWAS. The correction is appropriate for GWAS with case-control or quantitative outcomes. Our simulations and data example show that without correcting for sample overlap, the cmfdr is not properly controlled, leading to an excessive number of false discoveries and an excessive false discovery proportion. Our correction for sample overlap is effective in that it restores proper control of the false discovery rate, at very little loss in power. CONCLUSIONS: With our proposed correction, it is possible to integrate GWAS summary statistics with overlapping samples in a statistical framework that is dependent on the joint distribution of the two GWAS. Verena Zuber is supported by the Wellcome Trust and the Royal Society (Grant Number 204623/Z/16/Z) and the UK Medical Research Council (Grant Number MC_UU_00002/7).
Published: 2018
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49. AB0397 Prevalence and factors associated with depression among patients affected by chronic inflammatory arthritis: preliminary results of a single-centre experience in italy

Author: Alessandro Giollo, Chiara Bonetto, S. Pezzato, M.L. Marognolli, Sarah Tosato, M.G. Gnatta, Antonio Carletto, Federica Martinis, Doriana Cristofalo, S. Tomassi, Cristian Caimmi, and Elena Fracassi
Subjects: 030203 arthritis & rheumatology, 0301 basic medicine, medicine.medical_specialty, business.industry, Inflammatory arthritis, Arthritis, medicine.disease, Hospital Anxiety and Depression Scale, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Internal medicine, Cohort, medicine, History of depression, Anxiety, medicine.symptom, business, Disease burden, Depression (differential diagnoses)
Abstract: Background Depression and anxiety disorders are more common in chronic inflammatory arthritides (CIA) than in the general population.1 In rheumatoid arthritis (RA), depressive and anxiety symptoms have been associated with disease activity and pain perception,1 physical disability,2 health care costs,3 and mortality.4 To our knowledge, data on the prevalence of depression in Italian patients with RA are scarce. Objectives To estimate the prevalence and factors associated with depression among patients affected by RA. Methods During an one year period, patients affected by RA have been consecutively enrolled. For each patient demographics and disease characteristics were recorded; the Hospital Anxiety and Depression Scale (HADS) was administered. HADS is a validate questionnaire to assess depressive and anxiety symptoms in patients affected by somatic disorders admitted to general hospital. An HADS ≥11 was considered diagnostic for depression. Results The table summarises the main results. We recruited 231 patients affected by RA, finding a prevalence of depression of 13.9% (95% CI 9.4%–18.3%). Overall, patients with depression, when compared with patients without, were older, more frequently females, with a lower education, higher physician global assessment and patient global assessment, more comorbidities. In particular, they had any cardiovascular, neurologic or musculoskeletal issue (p=0.018, p=0.032, p=0.014, respectively) and more often used glucocorticoids or NSAIDs. Conversely, no association was found between depressive symptoms and the use of biologic therapies or the presence of inflammatory markers. Interestingly, a positive history of depression was present only in few patients with an HADS ≥11. Conclusions These preliminary results suggest that more than one every seven patients with RA could suffer from depression, thus depression might be undiagnosed in a significant number of patients. Comorbidities, anti-inflammatory medications and both physician- and patient- driven evaluation of disease burden were the most striking factors associated with depression in this cohort of patients with RA. References [1] Kojima M, et al. Arthritis and rheumatism2009Aug 15;61(8):1018–24. [2] Peck JR, et al. Arthritis and rheumatism1989Sep;32(9):1100–6. [3] Joyce AT, et al. J Rheumatol2009Apr;36(4):743–52. [4] Ang DC, et al. J Rheumatol2005Jun;32(6):1013–9. Disclosure of Interest None declared
Published: 2018
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50. Prevalence of non-psychotic disorders in ultra-high risk individuals and transition to psychosis: A systematic review

Author: Giuseppe Maina, Umberto Albert, S. Tomassi, Sarah Tosato, Albert, Umberto, Tomassi, Simona, Maina, Giuseppe, and Tosato, Sarah
Subjects: Risk, Prevalence rates, Psychosis, Transition rates, Ultra-high risk, Psychiatry and Mental Health, Biological Psychiatry, medicine.medical_specialty, prevalence rates, Prevalence, Psychosi, Comorbidity, Ultra high risk, ultra-high risk, 03 medical and health sciences, 0302 clinical medicine, psychosis, transition rates, Intervention (counseling), medicine, Humans, Psychiatry, Psychiatric Status Rating Scales, business.industry, Transition rate, Mental Disorders, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Psychotic Disorders, Prevalence rate, Disease Progression, business, 030217 neurology & neurosurgery
Abstract: Despite the growing interest in the prodromes of psychosis, the proper identification of those Ultra High Risk (UHR) subjects who will convert to psychosis remains an unresolved issue. It remains to be fully understood whether the risk of transition to psychosis is incremented by the concomitant presence of non-psychotic symptoms. We performed a systematic review in order to estimate: prevalence rates of non-psychotic disorders in UHR individuals and whether any comorbid disorder impacts on the risk of transition to frank psychosis. The review was conducted using the PRISMA guidelines by searching PubMed until August 2017. The inclusion criteria were: studies with appropriate definition of UHR/ ARMS (At Risk Mental States for psychosis); cross-sectional design (for prevalence rates) or longitudinal design (for transition rates to psychosis); adolescents and/or adults; specified instrument/interview for the diagnosis of mental disorder/symptoms. We included 46 English-language articles. We found that non-psychotic symptoms are a prevalent concern in UHR individuals, and this is true for all comorbid disorders examined. None of the mental disorder examined appear to be a marker for transition to psychosis. Our systematic review found that the great majority of UHR individuals actually has a highly prevalent clearly defined, above-the-threshold mental disorder that should constitute the primary focus of intervention.
Published: 2018

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