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2. Metabolic activity of CYP2C19 and CYP2D6 on antidepressant response from 13 clinical studies using genotype imputation: a meta-analysis

Author

Li, Danyang, Pain, Oliver, Fabbri, Chiara, Wong, Win Lee Edwin, Lo, Chris Wai Hang, Ripke, Stephan, Cattaneo, Annamaria, Souery, Daniel, Dernovsek, Mojca Z., Henigsberg, Neven, Hauser, Joanna, Lewis, Glyn, Mors, Ole, Perroud, Nader, Rietschel, Marcella, Uher, Rudolf, Maier, Wolfgang, Baune, Bernhard T., Biernacka, Joanna M., Bondolfi, Guido, Domschke, Katharina, Kato, Masaki, Liu, Yu-Li, Serretti, Alessandro, Tsai, Shih-Jen, Weinshilboum, Richard, McIntosh, Andrew M., and Lewis, Cathryn M.

Published
2024
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3. Correction: Metabolic activity of CYP2C19 and CYP2D6 on antidepressant response from 13 clinical studies using genotype imputation: a meta-analysis

Author

Li, Danyang, Pain, Oliver, Fabbri, Chiara, Wong, Win Lee Edwin, Lo, Chris Wai Hang, Ripke, Stephan, Cattaneo, Annamaria, Souery, Daniel, Dernovsek, Mojca Z., Henigsberg, Neven, Hauser, Joanna, Lewis, Glyn, Mors, Ole, Perroud, Nader, Rietschel, Marcella, Uher, Rudolf, Maier, Wolfgang, Baune, Bernhard T., Biernacka, Joanna M., Bondolfi, Guido, Domschke, Katharina, Kato, Masaki, Liu, Yu-Li, Serretti, Alessandro, Tsai, Shih-Jen, Weinshilboum, Richard, McIntosh, Andrew M., and Lewis, Cathryn M.

Published
2024
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4. Metabolic activity of CYP2C19 and CYP2D6 on antidepressant response from 13 clinical studies using genotype imputation: a meta-analysis

Author

Danyang Li, Oliver Pain, Chiara Fabbri, Win Lee Edwin Wong, Chris Wai Hang Lo, Stephan Ripke, Annamaria Cattaneo, Daniel Souery, Mojca Z. Dernovsek, Neven Henigsberg, Joanna Hauser, Glyn Lewis, Ole Mors, Nader Perroud, Marcella Rietschel, Rudolf Uher, Wolfgang Maier, Bernhard T. Baune, Joanna M. Biernacka, Guido Bondolfi, Katharina Domschke, Masaki Kato, Yu-Li Liu, Alessandro Serretti, Shih-Jen Tsai, Richard Weinshilboum, the GSRD Consortium, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Andrew M. McIntosh, and Cathryn M. Lewis

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract Cytochrome P450 enzymes including CYP2C19 and CYP2D6 are important for antidepressant metabolism and polymorphisms of these genes have been determined to predict metabolite levels. Nonetheless, more evidence is needed to understand the impact of genetic variations on antidepressant response. In this study, individual clinical and genetic data from 13 studies of European and East Asian ancestry populations were collected. The antidepressant response was clinically assessed as remission and percentage improvement. Imputed genotype was used to translate genetic polymorphisms to metabolic phenotypes (poor, intermediate, normal, and rapid+ultrarapid) of CYP2C19 and CYP2D6. CYP2D6 structural variants cannot be imputed from genotype data, limiting the determination of metabolic phenotypes, and precluding testing for association with response. The association of CYP2C19 metabolic phenotypes with treatment response was examined using normal metabolizers as the reference. Among 5843 depression patients, a higher remission rate was found in CYP2C19 poor metabolizers compared to normal metabolizers at nominal significance but did not survive after multiple testing correction (OR = 1.46, 95% CI [1.03, 2.06], p = 0.033, heterogeneity I2 = 0%, subgroup difference p = 0.72). No metabolic phenotype was associated with percentage improvement from baseline. After stratifying by antidepressants primarily metabolized by CYP2C19, no association was found between metabolic phenotypes and antidepressant response. Metabolic phenotypes showed differences in frequency, but not effect, between European- and East Asian-ancestry studies. In conclusion, metabolic phenotypes imputed from genetic variants using genotype were not associated with antidepressant response. CYP2C19 poor metabolizers could potentially contribute to antidepressant efficacy with more evidence needed. Sequencing and targeted pharmacogenetic testing, alongside information on side effects, antidepressant dosage, depression measures, and diverse ancestry studies, would more fully capture the influence of metabolic phenotypes.

Published
2024
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7. Telomere length and mitochondrial DNA copy number in association with trauma-focused psychotherapy efficacy

Author

Baune, Bernhard T., Minelli, Alessandra, Serretti, Alessandro, Dierssen, Mara, Maron, Eduard, Potier, Marie-Claude, Gennarelli, Massimo, van Westrhenen, Roos, Squassina, Alessio, Stacey, David, Mehta, Divja, Janzing, JoostG. E., Ebert, Bjarke, Fabbri, Chiara, Lio’, Pietro, Rybakowski, Filip, Pisanu, Claudia, Meloni, Anna, Bortolomasi, Marco, Zampieri, Elisa, Congiu, Donatella, Lana, Beatrice, Manchia, Mirko, Meattini, Mattia, and Paribello, Pasquale

Published
2025
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9. Multimodal brain-derived subtypes of Major depressive disorder differentiate patients for anergic symptoms, immune-inflammatory markers, history of childhood trauma and treatment-resistance

Author

Colombo, Federica, Calesella, Federico, Bravi, Beatrice, Fortaner-Uyà, Lidia, Monopoli, Camilla, Tassi, Emma, Carminati, Matteo, Zanardi, Raffaella, Bollettini, Irene, Poletti, Sara, Lorenzi, Cristina, Spadini, Sara, Brambilla, Paolo, Serretti, Alessandro, Maggioni, Eleonora, Fabbri, Chiara, Benedetti, Francesco, and Vai, Benedetta

Published
2024
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13. Correction: Metabolic activity of CYP2C19 and CYP2D6 on antidepressant response from 13 clinical studies using genotype imputation: a meta-analysis

Author

Danyang Li, Oliver Pain, Chiara Fabbri, Win Lee Edwin Wong, Chris Wai Hang Lo, Stephan Ripke, Annamaria Cattaneo, Daniel Souery, Mojca Z. Dernovsek, Neven Henigsberg, Joanna Hauser, Glyn Lewis, Ole Mors, Nader Perroud, Marcella Rietschel, Rudolf Uher, Wolfgang Maier, Bernhard T. Baune, Joanna M. Biernacka, Guido Bondolfi, Katharina Domschke, Masaki Kato, Yu-Li Liu, Alessandro Serretti, Shih-Jen Tsai, Richard Weinshilboum, the GSRD Consortium, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Andrew M. McIntosh, and Cathryn M. Lewis

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Published
2024
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14. Precision Medicine in Antidepressants Treatment

Author

Tsermpini, Evangelia Eirini, Serretti, Alessandro, Dolžan, Vita, Michel, Martin C., Editor-in-Chief, Barrett, James E., Editorial Board Member, Centurión, David, Editorial Board Member, Flockerzi, Veit, Editorial Board Member, Geppetti, Pierangelo, Editorial Board Member, Hofmann, Franz B., Editorial Board Member, Meier, Kathryn Elaine, Editorial Board Member, Page, Clive P., Editorial Board Member, Wang, KeWei, Editorial Board Member, Cascorbi, Ingolf, editor, and Schwab, Matthias, editor

Published
2023
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16. Polygenic scores of subcortical brain volumes as possible modulators of treatment response in depression

Author

Potier, Marie-Claude, van Westrhenen, Roos, Rybakowski, Filip, Mehta, Divya, Dierssen, Mara, Janzing, Joost G.E., Liò, Pietro, Oliva, Vincenzo, Martone, Alfonso, Fanelli, Giuseppe, Domschke, Katharina, Minelli, Alessandra, Gennarelli, Massimo, Martini, Paolo, Bortolomasi, Marco, Maron, Eduard, Squassina, Alessio, Pisanu, Claudia, Kasper, Siegfried, Zohar, Joseph, Souery, Daniel, Montgomery, Stuart, Albani, Diego, Forloni, Gianluigi, Ferentinos, Panagiotis, Rujescu, Dan, Mendlewicz, Julien, De Ronchi, Diana, Baune, Bernhard T., Serretti, Alessandro, and Fabbri, Chiara

Published
2024
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22. Multi-omics data integration methods and their applications in psychiatric disorders

Author

Sathyanarayanan, Anita, Mueller, Tamara T., Ali Moni, Mohammad, Schueler, Katja, Baune, Bernhard T., Lio, Pietro, Mehta, Divya, Baune, Bernhard T, Dierssen, Mara, Ebert, Bjarke, Fabbri, Chiara, Fusar-Poli, Paolo, Gennarelli, Massimo, Harmer, Catherine, Howes, Oliver D., Janzing, Joost G.E., Maron, Eduard, Minelli, Alessandra, Nonell, Lara, Pisanu, Claudia, Potier, Marie-Claude, Rybakowski, Filip, Serretti, Alessandro, Squassina, Alessio, Stacey, David, van Westrhenen, Roos, and Xicota, Laura

Published
2023
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26. Multilingualism and international mental health research–The barriers for non-native speakers of English

Author

de Girolamo, Giovanni, primary, Calza, Stefano, additional, Clerici, Massimo, additional, D’Agostino, Armando, additional, De Ronchi, Diana, additional, Fagiolini, Andrea, additional, Nicolò, Giuseppe, additional, Nobile, Maria, additional, Raballo, Andrea, additional, Rucci, Paola, additional, Serretti, Alessandro, additional, Starace, Fabrizio, additional, Tiraboschi, Pietro, additional, and Brambilla, Paolo, additional

Published
2024
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28. The link between cognition and somatic conditions related to insulin resistance in the UK Biobank study cohort: a systematic review

Author

Fanelli, Giuseppe, Mota, Nina Roth, Salas-Salvadó, Jordi, Bulló, Mònica, Fernandez-Aranda, Fernando, Camacho-Barcia, Lucía, Testa, Giulia, Jiménez-Murcia, Susana, Bertaina-Anglade, Valérie, Franke, Barbara, Poelmans, Geert, van Gils, Veerle, Jansen, Willemijn J., Vos, Stephanie J.B., Wimberley, Theresa, Dalsgaard, Søren, Barta, Csaba, Serretti, Alessandro, Fabbri, Chiara, and Bralten, Janita

Published
2022
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31. Is emotion dysregulation correlated to depressive and manic symptoms of bipolar disorder? Results from a systematic review and network meta-analysis

Author

V. Oliva, M. De Prisco, G. Fico, A. Murru, M. Fornaro, A. Serretti, J. Radua, and E. Vieta

Subjects
Psychiatry, RC435-571
Abstract

Introduction Emotion dysregulation (ED) is a multidimensional construct involving the lack of awareness, understanding and acceptance of emotions, a reduced access to adaptive and appropriate strategies to modulate the intensity or duration of emotional responses, and the inability to control behaviors in accordance with desired goals when experiencing negative emotions. ED is outlined in the general population and several psychiatric disorders, including bipolar disorder (BD), and influences its clinical course and management, quality of life, and daily social functioning. Objectives The objective of this systematic review was to examine the correlations between maladaptive (i.e., positive and negative rumination, negative focus, risk taking behaviors, suppression, and dampening) and adaptive (i.e., cognitive reframing, adaptive coping, and acceptance) strategies of emotion regulation (ER) and depressive and manic symptoms of BD. Methods We searched the literature from inception to April 12, 2022, and included studies focusing on ER/ED assessed with a validated scale. We conducted multiple pairwise meta-analyses for correlations between ED dimension (or overall ED) and the measures of depressive and manic symptoms of BD, and separate Bayesian network meta-analyses to examine which aspects of emotion regulation were most closely associated with depressive and manic symptoms of BD. The Pearson’s r coefficients were adjusted using sample-size weights and Fisher’s r-to-z transformed was conducted. Results A total of 13,826 records was identified and, after duplicate removal and title/abstract evaluation, 442 were explored at the full text. Sixteen studies were finally included. Results from pairwise meta-analyses are shown in Figure 1, results from network meta-analyses in Figure 2 and 3. Both depressive and manic BD symptomatology were found to be related to maladaptive ER strategies, with the only difference of positive rumination, associated only to manic symptoms. Negative rumination and risk-taking behaviors were the strategies more correlated to both manic and depressive symptoms, as confirmed by both pairwise metanalyses and network metanalyses. On the other hand, depressive symptomatology appeared more correlated with decreased adaptive strategies than manic symptomatology. Image: Image 2: Image 3: Conclusions ED has a significant correlation with BD symptomatology, therefore it should be explicitly considered during clinical assessment, diagnosis, and intervention on BD, and specific treatments should be implemented. More studies, and with longitudinal design, are needed to better explore these associations and their causal direction. In addition, future studies should mainly focus on the complex interactions between cognitive, social, and cultural aspects, and biological correlates to improve knowledge on a topic that is still poorly investigated. Disclosure of Interest V. Oliva: None Declared, M. De Prisco: None Declared, G. Fico Grant / Research support from: “La Caixa” Foundation (ID 100010434 - fellowship code LCF/BQ/DR21/11880019), Consultant of: Angelini, Janssen-Cilag and Lundbeck, A. Murru Grant / Research support from: Spanish Ministry of Science and Innovation (PI19/00672) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), Consultant of: Angelini, Idorsia, Lundbeck, Pfizer, Takeda, M. Fornaro: None Declared, A. Serretti Consultant of: Abbott, Abbvie, Angelini, AstraZeneca, Clinical Data, Boehringer, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Innovapharma, Italfarmaco, Janssen, Lundbeck, Naurex, Pfizer, Polifarma, Sanofi, Servier, and Taliaz, J. Radua Grant / Research support from: Spanish Ministry of Science and Innovation (PI19/00394, CPII19/00009) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER) and the Instituto de Salud Carlos III, E. Vieta Grant / Research support from: Spanish Ministry of Science and Innovation (PI18/00805, PI21/00787) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM); the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2017 SGR 1365), the CERCA Programme, and the Departament de Salut de la Generalitat de Catalunya for the PERIS grant SLT006/17/00357. Thanks the support of the European Union Horizon 2020 research and innovation program (EU.3.1.1. Understanding health, wellbeing and disease: Grant No 754907 and EU.3.1.3. Treating and managing disease: Grant No 945151), Consultant of: AB-Biotics, AbbVie, Angelini, Biogen, Boehringer-Ingelheim, Celon Pharma, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, Janssen, Lundbeck, Medincell, Novartis, Orion Corporation, Organon, Otsuka, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris

Published
2023
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32. Does bipolar disorder differ from other mental illnesses in terms of emotion dysregulation? A systematic review and meta-analysis

Author

M. De Prisco, V. Oliva, G. Fico, J. Radua, I. Grande, N. Roberto, G. Anmella, D. Hidalgo-Mazzei, M. Fornaro, A. de Bartolomeis, A. Serretti, E. Vieta, and A. Murru

Subjects
Psychiatry, RC435-571
Abstract

Introduction Emotion regulation (ER) is the ability to assess, monitor, or modify emotional reactions to achieve a goal (Gross. Psychological inquiry 2015; 26 1-26). When ER strategies are rigidly or maladaptively applied, emotional dysregulation (ED) can occur (Thompson. Development and psychopathology 2019; 31 805-815). ED is common in people diagnosed with bipolar disorder (BD), but it can also be described in other clinical populations given its transdiagnostic nature. Numerous aspects of ED have been described in BD (De Prisco et al. Neuroscience & Biobehavioral Reviews 2022; 104914), but it is unclear whether these manifest similarly in other conditions such as major depressive disorder (MDD) or borderline personality disorder (BPD), or whether they are specific to BD. Objectives The objective of this systematic review and meta-analysis is to examine the literature comparing BD with other psychiatric disorders in terms of ED, focusing on those studies using validated clinical tools. Methods A systematic search from inception to April 28th, 2022, was conducted exploring the PubMed/MEDLINE,EMBASE, Scopus, and PsycINFO databases. Those studies providing quantitative data on ED in people diagnosed with BD and compared with clinical groups were eligible for inclusion. No restriction about age, sample size, or language were applied. Random effect meta-analyses were conducted, and effect sizes were calculated as standardized mean differences (SMD). Results A total of 3,239 records was identified and, after duplicate removal and title/abstract evaluation, 112 were explored at the full text. Twenty-nine studies were finally included, and it was possible to perform a meta-analysis with twenty-two (145 comparisons) of them. Only studies comparing BD with MDD, and BPD provided sufficient data to perform a meta-analysis. People with BD did not differ from people with MDD in most of the comparisons considered. However, BD patients presented higher positive rumination (two comparisons: SMD=0.46; CI=0.27, 0.64; p=8.5e-07; I2=0%; and SMD=0.34; CI=0.15, 0.52; p=2.7e-04; I2=0%) and risk-taking behaviors (SMD=0.48; CI=0.27, 0.69; p=8.11e-06; I2=0%). In contrast, people with BPD displayed an overall higher degree of ED (SMD=-1.22; CI=-1.94, -0.5; p=9.1e-04; I2= 90.7) and used fewer adaptive ER strategies. Additionally, higher levels of self-blaming (SMD=-0.80; CI=-1.11, -0.50; p=2.68e-07; I2=0) and impulsive behavior (SMD=-0.76; CI=-0.89, -0.63; p=5.4e-29; I2=0) were observed. Image: Image 2: Conclusions ED is a trans-diagnostic construct that spans a continuum of different psychiatric disorders. Outlining the specific clinical features of one disorder versus another may help future research to increase our knowledge of these issues and develop new treatment strategies to reduce the clinical burden of these patients. Disclosure of Interest M. De Prisco: None Declared, V. Oliva: None Declared, G. Fico Grant / Research support from: “La Caixa” Foundation (ID 100010434 - fellowship code LCF/BQ/DR21/11880019), Consultant of: Angelini, Janssen-Cilag and Lundbeck, J. Radua Grant / Research support from: Spanish Ministry of Science and Innovation (PI19/00394, CPII19/00009) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER) and the Instituto de Salud Carlos III, I. Grande Grant / Research support from: Spanish Ministry of Science and Innovation (MCIN) (PI19/00954) integrated into the Plan Nacional de I+D+I and cofinanced by the ISCIII-Subdirección General de Evaluación y el Fondos Europeos de la Unión Europea (FEDER, FSE, Next Generation EU/Plan de Recuperación Transformación y Resiliencia_PRTR ); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM); and the the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2017 SGR 1365), CERCA Programme / Generalitat de Catalunya as well as the Fundació Clínic per la Recerca Biomèdica (Pons Bartran 2022-FRCB_PB1_2022), Consultant of: ADAMED, Angelini, Casen Recordati, Ferrer, Janssen Cilag, and Lundbeck, Lundbeck-Otsuka, Luye, SEI Healthcare, N. Roberto: None Declared, G. Anmella Grant / Research support from: Rio Hortega 2021 grant (CM21/00017) from the Spanish Ministry of Health financed by the Instituto de Salud Carlos III (ISCIII) and co-financed by the Fondo Social Europeo Plus (FSE+), Consultant of: Janssen-Cilag, Lundbeck, Lundbeck/Otsuka, and Angelini, D. Hidalgo-Mazzei Grant / Research support from: Juan Rodés JR18/00021 granted by the Instituto de Salud Carlos III (ISCIII), M. Fornaro: None Declared, A. de Bartolomeis Consultant of: Janssen, Lundbeck, and Otsuka and lecture fees for educational meeting from Chiesi, Lundbeck, Roche, Sunovion, Vitria, Recordati, Angelini and Takeda; he has served on advisory boards for Eli Lilly, Jansen, Lundbeck, Otsuka, Roche, and Takeda, Chiesi, Recordati, Angelini, Vitria, A. Serretti Consultant of: Abbott, Abbvie, Angelini, AstraZeneca, Clinical Data, Boehringer, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Innovapharma, Italfarmaco, Janssen, Lundbeck, Naurex, Pfizer, Polifarma, Sanofi, Servier, and Taliaz, E. Vieta Grant / Research support from: Spanish Ministry of Science and Innovation (PI18/00805, PI21/00787) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM); the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2017 SGR 1365), the CERCA Programme, and the Departament de Salut de la Generalitat de Catalunya for the PERIS grant SLT006/17/00357. Thanks the support of the European Union Horizon 2020 research and innovation program (EU.3.1.1. Understanding health, wellbeing and disease: Grant No 754907 and EU.3.1.3. Treating and managing disease: Grant No 945151), Consultant of: AB-Biotics, AbbVie, Angelini, Biogen, Boehringer-Ingelheim, Celon Pharma, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, Janssen, Lundbeck, Medincell, Novartis, Orion Corporation, Organon, Otsuka, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris, A. Murru Grant / Research support from: Spanish Ministry of Science and Innovation (PI19/00672) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), Consultant of: Angelini, Idorsia, Lundbeck, Pfizer, Takeda

Published
2023
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35. Expert consensus recommendations on the use of randomized clinical trials for drug approval in psychiatry- comparing trial designs

Author

Similon, Miriam von Mücke, Paasche, Cecilia, Krol, Fas, Lerer, Bernard, Goodwin, Guy M., Berk, Michael, Meyer-Lindenberg, Andreas, Ketter, Terence A., Yatham, Lakshmi N., Goldberg, Joseph F., Malhi, Gin S., El-Mallakh, Rif, Licht, Rasmus W., Young, Allan H., Kapczinski, Flavio, Swartz, Marnina, Hagin, Michal, Torrent, Carla, Serretti, Alessandro, Yildiz, Ayşegül, Martínez-Arán, Anabel, Strejilevich, Sergio, Rybakowski, Janusz, Sani, Gabriele, Grunze, Heinz, Vázquez, Gustavo, Pinto, Ana Gonzales, Azorin, Jean Michel, Nolen, Willem, Sentissi, Othman, López-Jaramillo, Carlos, Frey, Benicio N., Nierenberg, Andrew, Parker, Gordon, Bond, David J, Cohen, Adam, Tortorella, Alfonso, Perugi, Giulio, Vieta, Eduard, and Popovic, Dina

Published
2022
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36. Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Author

Trubetskoy, Vassily, Pardiñas, Antonio F., Qi, Ting, Panagiotaropoulou, Georgia, Awasthi, Swapnil, Bigdeli, Tim B., Bryois, Julien, Chen, Chia-Yen, Dennison, Charlotte A., Hall, Lynsey S., Lam, Max, Watanabe, Kyoko, Frei, Oleksandr, Ge, Tian, Harwood, Janet C., Koopmans, Frank, Magnusson, Sigurdur, Richards, Alexander L., Sidorenko, Julia, Wu, Yang, Zeng, Jian, Grove, Jakob, Kim, Minsoo, Li, Zhiqiang, Voloudakis, Georgios, Zhang, Wen, Adams, Mark, Agartz, Ingrid, Atkinson, Elizabeth G., Agerbo, Esben, Al Eissa, Mariam, Albus, Margot, Alexander, Madeline, Alizadeh, Behrooz Z., Alptekin, Köksal, Als, Thomas D., Amin, Farooq, Arolt, Volker, Arrojo, Manuel, Athanasiu, Lavinia, Azevedo, Maria Helena, Bacanu, Silviu A., Bass, Nicholas J., Begemann, Martin, Belliveau, Richard A., Bene, Judit, Benyamin, Beben, Bergen, Sarah E., Blasi, Giuseppe, Bobes, Julio, Bonassi, Stefano, Braun, Alice, Bressan, Rodrigo Affonseca, Bromet, Evelyn J., Bruggeman, Richard, Buckley, Peter F., Buckner, Randy L., Bybjerg-Grauholm, Jonas, Cahn, Wiepke, Cairns, Murray J., Calkins, Monica E., Carr, Vaughan J., Castle, David, Catts, Stanley V., Chambert, Kimberley D., Chan, Raymond C. K., Chaumette, Boris, Cheng, Wei, Cheung, Eric F. C., Chong, Siow Ann, Cohen, David, Consoli, Angèle, Cordeiro, Quirino, Costas, Javier, Curtis, Charles, Davidson, Michael, Davis, Kenneth L., de Haan, Lieuwe, Degenhardt, Franziska, DeLisi, Lynn E., Demontis, Ditte, Dickerson, Faith, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Duan, Jubao, Ducci, Giuseppe, Dudbridge, Frank, Eriksson, Johan G., Fañanás, Lourdes, Faraone, Stephen V., Fiorentino, Alessia, Forstner, Andreas, Frank, Josef, Freimer, Nelson B., Fromer, Menachem, Frustaci, Alessandra, Gadelha, Ary, Genovese, Giulio, Gershon, Elliot S., Giannitelli, Marianna, Giegling, Ina, Giusti-Rodríguez, Paola, Godard, Stephanie, Goldstein, Jacqueline I., González Peñas, Javier, González-Pinto, Ana, Gopal, Srihari, Gratten, Jacob, Green, Michael F., Greenwood, Tiffany A., Guillin, Olivier, Gülöksüz, Sinan, Gur, Raquel E., Gur, Ruben C., Gutiérrez, Blanca, Hahn, Eric, Hakonarson, Hakon, Haroutunian, Vahram, Hartmann, Annette M., Harvey, Carol, Hayward, Caroline, Henskens, Frans A., Herms, Stefan, Hoffmann, Per, Howrigan, Daniel P., Ikeda, Masashi, Iyegbe, Conrad, Joa, Inge, Julià, Antonio, Kähler, Anna K., Kam-Thong, Tony, Kamatani, Yoichiro, Karachanak-Yankova, Sena, Kebir, Oussama, Keller, Matthew C., Kelly, Brian J., Khrunin, Andrey, Kim, Sung-Wan, Klovins, Janis, Kondratiev, Nikolay, Konte, Bettina, Kraft, Julia, Kubo, Michiaki, Kučinskas, Vaidutis, Kučinskiene, Zita Ausrele, Kusumawardhani, Agung, Kuzelova-Ptackova, Hana, Landi, Stefano, Lazzeroni, Laura C., Lee, Phil H., Legge, Sophie E., Lehrer, Douglas S., Lencer, Rebecca, Lerer, Bernard, Li, Miaoxin, Lieberman, Jeffrey, Light, Gregory A., Limborska, Svetlana, Liu, Chih-Min, Lönnqvist, Jouko, Loughland, Carmel M., Lubinski, Jan, Luykx, Jurjen J., Lynham, Amy, Macek, Jr, Milan, Mackinnon, Andrew, Magnusson, Patrik K. E., Maher, Brion S., Maier, Wolfgang, Malaspina, Dolores, Mallet, Jacques, Marder, Stephen R., Marsal, Sara, Martin, Alicia R., Martorell, Lourdes, Mattheisen, Manuel, McCarley, Robert W., McDonald, Colm, McGrath, John J., Medeiros, Helena, Meier, Sandra, Melegh, Bela, Melle, Ingrid, Mesholam-Gately, Raquelle I., Metspalu, Andres, Michie, Patricia T., Milani, Lili, Milanova, Vihra, Mitjans, Marina, Molden, Espen, Molina, Esther, Molto, María Dolores, Mondelli, Valeria, Moreno, Carmen, Morley, Christopher P., Muntané, Gerard, Murphy, Kieran C., Myin-Germeys, Inez, Nenadić, Igor, Nestadt, Gerald, Nikitina-Zake, Liene, Noto, Cristiano, Nuechterlein, Keith H., O’Brien, Niamh Louise, O’Neill, F. Anthony, Oh, Sang-Yun, Olincy, Ann, Ota, Vanessa Kiyomi, Pantelis, Christos, Papadimitriou, George N., Parellada, Mara, Paunio, Tiina, Pellegrino, Renata, Periyasamy, Sathish, Perkins, Diana O., Pfuhlmann, Bruno, Pietiläinen, Olli, Pimm, Jonathan, Porteous, David, Powell, John, Quattrone, Diego, Quested, Digby, Radant, Allen D., Rampino, Antonio, Rapaport, Mark H., Rautanen, Anna, Reichenberg, Abraham, Roe, Cheryl, Roffman, Joshua L., Roth, Julian, Rothermundt, Matthias, Rutten, Bart P. F., Saker-Delye, Safaa, Salomaa, Veikko, Sanjuan, Julio, Santoro, Marcos Leite, Savitz, Adam, Schall, Ulrich, Scott, Rodney J., Seidman, Larry J., Sharp, Sally Isabel, Shi, Jianxin, Siever, Larry J., Sigurdsson, Engilbert, Sim, Kang, Skarabis, Nora, Slominsky, Petr, So, Hon-Cheong, Sobell, Janet L., Söderman, Erik, Stain, Helen J., Steen, Nils Eiel, Steixner-Kumar, Agnes A., Stögmann, Elisabeth, Stone, William S., Straub, Richard E., Streit, Fabian, Strengman, Eric, Stroup, T. Scott, Subramaniam, Mythily, Sugar, Catherine A., Suvisaari, Jaana, Svrakic, Dragan M., Swerdlow, Neal R., Szatkiewicz, Jin P., Ta, Thi Minh Tam, Takahashi, Atsushi, Terao, Chikashi, Thibaut, Florence, Toncheva, Draga, Tooney, Paul A., Torretta, Silvia, Tosato, Sarah, Tura, Gian Battista, Turetsky, Bruce I., Üçok, Alp, Vaaler, Arne, van Amelsvoort, Therese, van Winkel, Ruud, Veijola, Juha, Waddington, John, Walter, Henrik, Waterreus, Anna, Webb, Bradley T., Weiser, Mark, Williams, Nigel M., Witt, Stephanie H., Wormley, Brandon K., Wu, Jing Qin, Xu, Zhida, Yolken, Robert, Zai, Clement C., Zhou, Wei, Zhu, Feng, Zimprich, Fritz, Atbaşoğlu, Eşref Cem, Ayub, Muhammad, Benner, Christian, Bertolino, Alessandro, Black, Donald W., Bray, Nicholas J., Breen, Gerome, Buccola, Nancy G., Byerley, William F., Chen, Wei J., Cloninger, C. Robert, Crespo-Facorro, Benedicto, Donohoe, Gary, Freedman, Robert, Galletly, Cherrie, Gandal, Michael J., Gennarelli, Massimo, Hougaard, David M., Hwu, Hai-Gwo, Jablensky, Assen V., McCarroll, Steven A., Moran, Jennifer L., Mors, Ole, Mortensen, Preben B., Müller-Myhsok, Bertram, Neil, Amanda L., Nordentoft, Merete, Pato, Michele T., Petryshen, Tracey L., Pirinen, Matti, Pulver, Ann E., Schulze, Thomas G., Silverman, Jeremy M., Smoller, Jordan W., Stahl, Eli A., Tsuang, Debby W., Vilella, Elisabet, Wang, Shi-Heng, Xu, Shuhua, Adolfsson, Rolf, Arango, Celso, Baune, Bernhard T., Belangero, Sintia Iole, Børglum, Anders D., Braff, David, Bramon, Elvira, Buxbaum, Joseph D., Campion, Dominique, Cervilla, Jorge A., Cichon, Sven, Collier, David A., Corvin, Aiden, Curtis, David, Forti, Marta Di, Domenici, Enrico, Ehrenreich, Hannelore, Escott-Price, Valentina, Esko, Tõnu, Fanous, Ayman H., Gareeva, Anna, Gawlik, Micha, Gejman, Pablo V., Gill, Michael, Glatt, Stephen J., Golimbet, Vera, Hong, Kyung Sue, Hultman, Christina M., Hyman, Steven E., Iwata, Nakao, Jönsson, Erik G., Kahn, René S., Kennedy, James L., Khusnutdinova, Elza, Kirov, George, Knowles, James A., Krebs, Marie-Odile, Laurent-Levinson, Claudine, Lee, Jimmy, Lencz, Todd, Levinson, Douglas F., Li, Qingqin S., Liu, Jianjun, Malhotra, Anil K., Malhotra, Dheeraj, McIntosh, Andrew, McQuillin, Andrew, Menezes, Paulo R., Morgan, Vera A., Morris, Derek W., Mowry, Bryan J., Murray, Robin M., Nimgaonkar, Vishwajit, Nöthen, Markus M., Ophoff, Roel A., Paciga, Sara A., Palotie, Aarno, Pato, Carlos N., Qin, Shengying, Rietschel, Marcella, Riley, Brien P., Rivera, Margarita, Rujescu, Dan, Saka, Meram C., Sanders, Alan R., Schwab, Sibylle G., Serretti, Alessandro, Sham, Pak C., Shi, Yongyong, St Clair, David, Stefánsson, Hreinn, Stefansson, Kari, Tsuang, Ming T., van Os, Jim, Vawter, Marquis P., Weinberger, Daniel R., Werge, Thomas, Wildenauer, Dieter B., Yu, Xin, Yue, Weihua, Holmans, Peter A., Pocklington, Andrew J., Roussos, Panos, Vassos, Evangelos, Verhage, Matthijs, Visscher, Peter M., Yang, Jian, Posthuma, Danielle, Andreassen, Ole A., Kendler, Kenneth S., Owen, Michael J., Wray, Naomi R., Daly, Mark J., Huang, Hailiang, Neale, Benjamin M., Sullivan, Patrick F., Ripke, Stephan, Walters, James T. R., and O’Donovan, Michael C.

Published
2022
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39. Identifying the Common Genetic Basis of Antidepressant Response

Author

Oliver Pain, Karen Hodgson, Vassily Trubetskoy, Stephan Ripke, Victoria S. Marshe, Mark J. Adams, Enda M. Byrne, Adrian I. Campos, Tania Carrillo-Roa, Annamaria Cattaneo, Thomas D. Als, Daniel Souery, Mojca Z. Dernovsek, Chiara Fabbri, Caroline Hayward, Neven Henigsberg, Joanna Hauser, James L. Kennedy, Eric J. Lenze, Glyn Lewis, Daniel J. Müller, Nicholas G. Martin, Benoit H. Mulsant, Ole Mors, Nader Perroud, David J. Porteous, Miguel E. Rentería, Charles F. Reynolds, III, Marcella Rietschel, Rudolf Uher, Eleanor M. Wigmore, Wolfgang Maier, Naomi R. Wray, Katherine J. Aitchison, Volker Arolt, Bernhard T. Baune, Joanna M. Biernacka, Guido Bondolfi, Katharina Domschke, Masaki Kato, Qingqin S. Li, Yu-Li Liu, Alessandro Serretti, Shih-Jen Tsai, Gustavo Turecki, Richard Weinshilboum, Andrew M. McIntosh, Cathryn M. Lewis, Siegfried Kasper, Joseph Zohar, Stuart Montgomery, Diego Albani, Gianluigi Forloni, Panagiotis Ferentinos, Dan Rujescu, Julien Mendlewicz, Manuel Mattheisen, Maciej Trzaskowski, Abdel Abdellaoui, Esben Agerbo, Tracy M. Air, Till F.M. Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Tim B. Bigdeli, Elisabeth B. Binder, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Enrique Castelao, Jane Hvarregaard Christensen, Toni-Kim Clarke, Jonathan R.I. Coleman, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E. Crawford, Gail Davies, Ian J. Deary, Franziska Degenhardt, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Jerome C. Foo, Andreas J. Forstner, Josef Frank, Héléna A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hickie, Per Hoffmann, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Hougaard, David M. Howard, Marcus Ising, Rick Jansen, Ian Jones, Lisa A. Jones, Eric Jorgenson, James A. Knowles, 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, Lili Milani, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Niamh Mullins, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O’Reilly, Hogni Oskarsson, Michael J. Owen, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Wouter J. Peyrot, Giorgio Pistis, Danielle Posthuma, Jorge A. Quiroz, Per Qvist, John P. Rice, Brien P. Riley, Margarita Rivera, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Jianxin Shi, Stanley I. Shyn, Engilbert Sigurdsson, Grant C.B. Sinnamon, Johannes H. Smit, Daniel J. Smith, Hreinn Stefansson, Stacy Steinberg, Fabian Streit, Jana Strohmaier, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, André G. Uitterlinden, Daniel Umbricht, Sandra Van der Auwera, Albert M. van Hemert, Alexander Viktorin, Peter M. Visscher, Yunpeng Wang, Bradley T. Webb, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Stephanie H. Witt, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Klaus Berger, Dorret I. Boomsma, Sven Cichon, Udo Dannlowski, E.J.C. de Geus, J. Raymond DePaulo, Enrico Domenici, Tõnu Esko, Hans J. Grabe, Steven P. Hamilton, Andrew C. Heath, Kenneth S. Kendler, Stefan Kloiber, Susanne Lucae, Pamela A.F. Madden, Patrik K. Magnusson, Andres Metspalu, Preben Bo Mortensen, Bertram Müller-Myhsok, Merete Nordentoft, Markus M. Nöthen, Michael C. O’Donovan, Sara A. Paciga, Nancy L. Pedersen, Brenda W.J.H. Penninx, Roy H. Perlis, James B. Potash, Martin Preisig, Catherine Schaefer, Thomas G. Schulze, Jordan W. Smoller, Kari Stefansson, Henning Tiemeier, Henry Völzke, Myrna M. Weissman, Thomas Werge, Douglas F. Levinson, Gerome Breen, Anders D. Børglum, and Patrick F. Sullivan

Subjects
Antidepressant response, Depression, Genetics, GWAS, MDD, Polygenic score, Psychiatry, RC435-571
Abstract

Background: Antidepressants are a first-line treatment for depression. However, only a third of individuals experience remission after the first treatment. Common genetic variation, in part, likely regulates antidepressant response, yet the success of previous genome-wide association studies has been limited by sample size. This study performs the largest genetic analysis of prospectively assessed antidepressant response in major depressive disorder to gain insight into the underlying biology and enable out-of-sample prediction. Methods: Genome-wide analysis of remission (nremit = 1852, nnonremit = 3299) and percentage improvement (n = 5218) was performed. Single nucleotide polymorphism–based heritability was estimated using genome-wide complex trait analysis. Genetic covariance with eight mental health phenotypes was estimated using polygenic scores/AVENGEME. Out-of-sample prediction of antidepressant response polygenic scores was assessed. Gene-level association analysis was performed using MAGMA and transcriptome-wide association study. Tissue, pathway, and drug binding enrichment were estimated using MAGMA. Results: Neither genome-wide association study identified genome-wide significant associations. Single nucleotide polymorphism–based heritability was significantly different from zero for remission (h2 = 0.132, SE = 0.056) but not for percentage improvement (h2 = −0.018, SE = 0.032). Better antidepressant response was negatively associated with genetic risk for schizophrenia and positively associated with genetic propensity for educational attainment. Leave-one-out validation of antidepressant response polygenic scores demonstrated significant evidence of out-of-sample prediction, though results varied in external cohorts. Gene-based analyses identified ETV4 and DHX8 as significantly associated with antidepressant response. Conclusions: This study demonstrates that antidepressant response is influenced by common genetic variation, has a genetic overlap schizophrenia and educational attainment, and provides a useful resource for future research. Larger sample sizes are required to attain the potential of genetics for understanding and predicting antidepressant response.

Published
2022
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41. Identifying the Common Genetic Basis of Antidepressant Response

Author

Kasper, Siegfried, Zohar, Joseph, Souery, Daniel, Montgomery, Stuart, Albani, Diego, Forloni, Gianluigi, Ferentinos, Panagiotis, Rujescu, Dan, Mendlewicz, Julien, Wray, Naomi R., Ripke, Stephan, Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Adams, Mark J., Agerbo, Esben, Air, Tracy M., Andlauer, Till F.M., Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T.F., Bigdeli, Tim B., Binder, Elisabeth B., Bryois, Julien, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Coleman, Jonathan R.I., Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Deary, Ian J., Degenhardt, Franziska, Derks, Eske M., Direk, Nese, Dolan, Conor V., Dunn, Erin C., Eley, Thalia C., Escott-Price, Valentina, Hassan Kiadeh, Farnush Farhadi, Finucane, Hilary K., Foo, Jerome C., Forstner, Andreas J., Frank, Josef, Gaspar, Héléna A., Gill, Michael, Goes, Fernando S., Gordon, Scott D., Grove, Jakob, Hall, Lynsey S., Hansen, Christine Søholm, Hansen, Thomas F., Herms, Stefan, Hickie, Ian B., Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Hougaard, David M., Howard, David M., Ising, Marcus, Jansen, Rick, Jones, Ian, Jones, Lisa A., Jorgenson, Eric, Knowles, James A., Kohane, Isaac S., Kraft, Julia, Kretzschmar, Warren W., Kutalik, Zoltán, Li, Yihan, Lind, Penelope A., MacIntyre, Donald J., MacKinnon, Dean F., Maier, Robert M., Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E., Mehta, Divya, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mondimore, Francis M., Montgomery, Grant W., Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G., Nyholt, Dale R., O’Reilly, Paul F., Oskarsson, Hogni, Owen, Michael J., Painter, Jodie N., Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Peterson, Roseann E., Peyrot, Wouter J., Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A., Qvist, Per, Rice, John P., Riley, Brien P., Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C., Shen, Ling, Shi, Jianxin, Shyn, Stanley I., Sigurdsson, Engilbert, Sinnamon, Grant C.B., Smit, Johannes H., Smith, Daniel J., Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, André G., Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M., Viktorin, Alexander, Visscher, Peter M., Wang, Yunpeng, Webb, Bradley T., Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T., Berger, Klaus, Boomsma, Dorret I., Cichon, Sven, Dannlowski, Udo, de Geus, E.J.C., DePaulo, J. Raymond, Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Grabe, Hans J., Hamilton, Steven P., Hayward, Caroline, Heath, Andrew C., Kendler, Kenneth S., Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S., Lucae, Susanne, Madden, Pamela A.F., Magnusson, Patrik K., Martin, Nicholas G., McIntosh, Andrew M., Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, Nöthen, Markus M., O’Donovan, Michael C., Paciga, Sara A., Pedersen, Nancy L., Penninx, Brenda W.J.H., Perlis, Roy H., Porteous, David J., Potash, James B., Preisig, Martin, Rietschel, Marcella, Schaefer, Catherine, Schulze, Thomas G., Smoller, Jordan W., Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Weissman, Myrna M., Werge, Thomas, Lewis, Cathryn M., Levinson, Douglas F., Breen, Gerome, Børglum, Anders D., Sullivan, Patrick F., Pain, Oliver, Hodgson, Karen, Marshe, Victoria S., Campos, Adrian I., Carrillo-Roa, Tania, Cattaneo, Annamaria, Als, Thomas D., Dernovsek, Mojca Z., Fabbri, Chiara, Henigsberg, Neven, Hauser, Joanna, Kennedy, James L., Lenze, Eric J., Müller, Daniel J., Mulsant, Benoit H., Perroud, Nader, Rentería, Miguel E., Reynolds, Charles F., III, Wigmore, Eleanor M., Aitchison, Katherine J., Biernacka, Joanna M., Bondolfi, Guido, Kato, Masaki, Liu, Yu-Li, Serretti, Alessandro, Tsai, Shih-Jen, Turecki, Gustavo, and Weinshilboum, Richard

Published
2022
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44. Transcriptional biomarkers of response to pharmacological treatments in severe mental disorders: A systematic review

Author

Pisanu, Claudia, Severino, Giovanni, De Toma, Ilario, Dierssen, Mara, Fusar-Poli, Paolo, Gennarelli, Massimo, Lio, Pietro, Maffioletti, Elisabetta, Maron, Eduard, Mehta, Divya, Minelli, Alessandra, Potier, Marie-Claude, Serretti, Alessandro, Stacey, David, van Westrhenen, Roos, Xicota, Laura, Baune, Bernhard T, and Squassina, Alessio

Published
2022
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45. A meta-analysis of polygenic risk scores for mood disorders, neuroticism, and schizophrenia in antidepressant response

Author

Fanelli, Giuseppe, Domschke, Katharina, Minelli, Alessandra, Gennarelli, Massimo, Martini, Paolo, Bortolomasi, Marco, Maron, Eduard, Squassina, Alessio, Kasper, Siegfried, Zohar, Joseph, Souery, Daniel, Montgomery, Stuart, Albani, Diego, Forloni, Gianluigi, Ferentinos, Panagiotis, Rujescu, Dan, Mendlewicz, Julien, De Ronchi, Diana, Baune, Bernhard T, Serretti, Alessandro, and Fabbri, Chiara

Published
2022
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46. Insulinopathies of the brain? Genetic overlap between somatic insulin-related and neuropsychiatric disorders

Author

Giuseppe Fanelli, Barbara Franke, Ward De Witte, I. Hyun Ruisch, Jan Haavik, Veerle van Gils, Willemijn J. Jansen, Stephanie J. B. Vos, Lars Lind, Jan K. Buitelaar, Tobias Banaschewski, Søren Dalsgaard, Alessandro Serretti, Nina Roth Mota, Geert Poelmans, and Janita Bralten

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract The prevalence of somatic insulinopathies, like metabolic syndrome (MetS), obesity, and type 2 diabetes mellitus (T2DM), is higher in Alzheimer’s disease (AD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD). Dysregulation of insulin signalling has been implicated in these neuropsychiatric disorders, and shared genetic factors might partly underlie this observed multimorbidity. We investigated the genetic overlap between AD, ASD, and OCD with MetS, obesity, and T2DM by estimating pairwise global genetic correlations using the summary statistics of the largest available genome-wide association studies for these phenotypes. Having tested these hypotheses, other potential brain “insulinopathies” were also explored by estimating the genetic relationship of six additional neuropsychiatric disorders with nine insulin-related diseases/traits. Stratified covariance analyses were then performed to investigate the contribution of insulin-related gene sets. Significant negative genetic correlations were found between OCD and MetS (r g = −0.315, p = 3.9 × 10−8), OCD and obesity (r g = −0.379, p = 3.4 × 10−5), and OCD and T2DM (r g = −0.172, p = 3 × 10−4). Significant genetic correlations with insulin-related phenotypes were also found for anorexia nervosa (AN), attention-deficit/hyperactivity disorder (ADHD), major depressive disorder, and schizophrenia (p

Published
2022
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47. Age as a moderating factor of treatment resistance in depression

Author

Alexander Kautzky, Lucie Bartova, Gernot Fugger, Markus Dold, Daniel Souery, Stuart Montgomery, Joseph Zohar, Julien Mendlewicz, Chiara Fabbri, Alessandro Serretti, Dan Rujescu, and Siegfried Kasper

Subjects
treatment-resistant depression, antidepressant, sold age, Psychiatry, RC435-571
Abstract

Abstract Background Treatment-resistant depression (TRD) is an important clinical challenge and may present differently between age groups. Methods A total of 893 depressed patients recruited within the framework of the European research consortium “Group for the Studies of Resistant Depression” were assessed by generalized linear models regarding age effects (both as numerical and factorial predictors) on treatment outcome, number of lifetime depressive episodes, hospitalization time, and duration of the current episode. Effects of age as numerical predictor on the severity of common depressive symptoms, measured with Montgomery–Åsberg Depression Rating Scale (MADRS) for two-time points, were assessed by linear mixed models, respectively, for patients showing TRD and treatment response. A corrected p threshold of 0.001 was applied. Results Overall symptom load reflected by MADRS (p 4) for these items both before and after treatment (all p ≤ 0.001). Conclusions In this naturalistic sample of severely ill depressed patients, antidepressant treatment protocols were equally effective in addressing TRD in old age. However, specific symptoms such as sadness, appetite, and concentration showed an age-dependent presentation, impacting residual symptoms in severely affected TRD patients and calling for a precision approach by a better integration of age profiles in treatment recommendations.

Published
2023
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48. Shared genetics linking sociability with the brain's default mode network.

Author

Fanelli, Giuseppe, primary, Robinson, Jamie, additional, Fabbri, Chiara, additional, Bralten, Janita, additional, Mota, Nina Roth, additional, Arenella, Martina, additional, Sprooten, Emma, additional, Franke, Barbara, additional, Kas, Martien, additional, Andlauer, Till FM, additional, and Serretti, Alessandro, additional

Published
2024
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