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71 results on '"Stanley V. Catts"'

1. Reducing long-term antipsychotic use: a therapeutic dead end?

Author

Catts SV and O'Toole BI

Subjects
Humans, Antipsychotic Agents, Schizophrenia
Abstract

Competing Interests: Declaration of interestS.V.C. has received funding for acting in the role of an advisory board member, as a sponsored educational speaker, and for research projects from the following pharmaceutical companies: Janssen-Cilag Pty Ltd, Eli Lilly Australia Pty Ltd, Lundbeck Australia Pty Ltd, Novartis Pharmaceuticals Australia Pty Ltd, Pfizer Australia Pty Ltd, Bristol-Myers Squibb Pty Ltd, Sanofi-Aventis Australia Pty Ltd, Hospira Australia Pty Ltd, and AstraZeneca Pty Ltd. He is also a Trustee for the Psychosis Australia Trust and the Queensland Schizophrenia Research Foundation, and a board member of Clearthinking Queensland Ltd.

Published
2017
Full Text
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2. Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Author

Dick Schijven, Merel C. Postema, Masaki Fukunaga, Junya Matsumoto, Kenichiro Miura, Sonja M. C. de Zwarte, Neeltje E. M. van Haren, Wiepke Cahn, Hilleke E. Hulshoff Pol, René S. Kahn, Rosa Ayesa-Arriola, Víctor Ortiz-García de la Foz, Diana Tordesillas-Gutierrez, Javier Vázquez-Bourgon, Benedicto Crespo-Facorro, Dag Alnæs, Andreas Dahl, Lars T. Westlye, Ingrid Agartz, Ole A. Andreassen, Erik G. Jönsson, Peter Kochunov, Jason M. Bruggemann, Stanley V. Catts, Patricia T. Michie, Bryan J. Mowry, Yann Quidé, Paul E. Rasser, Ulrich Schall, Rodney J. Scott, Vaughan J. Carr, Melissa J. Green, Frans A. Henskens, Carmel M. Loughland, Christos Pantelis, Cynthia Shannon Weickert, Thomas W. Weickert, Lieuwe de Haan, Katharina Brosch, Julia-Katharina Pfarr, Kai G. Ringwald, Frederike Stein, Andreas Jansen, Tilo T. J. Kircher, Igor Nenadić, Bernd Krämer, Oliver Gruber, Theodore D. Satterthwaite, Juan Bustillo, Daniel H. Mathalon, Adrian Preda, Vince D. Calhoun, Judith M. Ford, Steven G. Potkin, Jingxu Chen, Yunlong Tan, Zhiren Wang, Hong Xiang, Fengmei Fan, Fabio Bernardoni, Stefan Ehrlich, Paola Fuentes-Claramonte, Maria Angeles Garcia-Leon, Amalia Guerrero-Pedraza, Raymond Salvador, Salvador Sarró, Edith Pomarol-Clotet, Valentina Ciullo, Fabrizio Piras, Daniela Vecchio, Nerisa Banaj, Gianfranco Spalletta, Stijn Michielse, Therese van Amelsvoort, Erin W. Dickie, Aristotle N. Voineskos, Kang Sim, Simone Ciufolini, Paola Dazzan, Robin M. Murray, Woo-Sung Kim, Young-Chul Chung, Christina Andreou, André Schmidt, Stefan Borgwardt, Andrew M. McIntosh, Heather C. Whalley, Stephen M. Lawrie, Stefan du Plessis, Hilmar K. Luckhoff, Freda Scheffler, Robin Emsley, Dominik Grotegerd, Rebekka Lencer, Udo Dannlowski, Jesse T. Edmond, Kelly Rootes-Murdy, Julia M. Stephen, Andrew R. Mayer, Linda A. Antonucci, Leonardo Fazio, Giulio Pergola, Alessandro Bertolino, Covadonga M. Díaz-Caneja, Joost Janssen, Noemi G. Lois, Celso Arango, Alexander S. Tomyshev, Irina Lebedeva, Simon Cervenka, Carl M. Sellgren, Foivos Georgiadis, Matthias Kirschner, Stefan Kaiser, Tomas Hajek, Antonin Skoch, Filip Spaniel, Minah Kim, Yoo Bin Kwak, Sanghoon Oh, Jun Soo Kwon, Anthony James, Geor Bakker, Christian Knöchel, Michael Stäblein, Viola Oertel, Anne Uhlmann, Fleur M. Howells, Dan J. Stein, Henk S. Temmingh, Ana M. Diaz-Zuluaga, Julian A. Pineda-Zapata, Carlos López-Jaramillo, Stephanie Homan, Ellen Ji, Werner Surbeck, Philipp Homan, Simon E. Fisher, Barbara Franke, David C. Glahn, Ruben C. Gur, Ryota Hashimoto, Neda Jahanshad, Eileen Luders, Sarah E. Medland, Paul M. Thompson, Jessica A. Turner, Theo G. M. van Erp, Clyde Francks, Neurology, and Child and Adolescent Psychiatry / Psychology

Subjects
subcortical, Neuroinformatics, Multidisciplinary, All institutes and research themes of the Radboud University Medical Center, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Schizophrenia, brain imaging, cortical, asymmetry
Abstract

Contains fulltext : 291574.pdf (Publisher’s version ) (Open Access) Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.

Published
2023

3. 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

4. White Matter Disruptions in Schizophrenia Are Spatially Widespread and Topologically Converge on Brain Network Hubs

Author

Stanley V. Catts, Chad A. Bousman, Alex Fornito, Paul Klauser, Simon T.E. Baker, Patricia T. Michie, Rhoshel K. Lenroot, Bryan J. Mowry, Carmel M. Loughland, Andrew Zalesky, Cynthia Shannon Weickert, Luca Cocchi, Vaughan J. Carr, Thomas W. Weickert, Janice M. Fullerton, Christos Pantelis, Ulrich Schall, Frans Henskens, Paul E. Rasser, and Vanessa Cropley

Subjects
Adult, Male, Adolescent, Schizoaffective disorder, Corpus callosum, Gyrus Cinguli, Corpus Callosum, White matter, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Thalamus, Neural Pathways, Fractional anisotropy, mental disorders, Connectome, medicine, Humans, Cingulum (brain), Aged, Cerebral Cortex, Regular Article, Middle Aged, medicine.disease, White Matter, 030227 psychiatry, Psychiatry and Mental health, Diffusion Tensor Imaging, medicine.anatomical_structure, Psychotic Disorders, Schizophrenia, Female, Nerve Net, Psychology, Neuroscience, 030217 neurology & neurosurgery, Diffusion MRI
Abstract

White matter abnormalities associated with schizophrenia have been widely reported, although the consistency of findings across studies is moderate. In this study, neuroimaging was used to investigate white matter pathology and its impact on whole-brain white matter connectivity in one of the largest samples of patients with schizophrenia. Fractional anisotropy (FA) and mean diffusivity (MD) were compared between patients with schizophrenia or schizoaffective disorder (n = 326) and age-matched healthy controls (n = 197). Between-group differences in FA and MD were assessed using voxel-based analysis and permutation testing. Automated whole-brain white matter fiber tracking and the network-based statistic were used to characterize the impact of white matter pathology on the connectome and its rich club. Significant reductions in FA associated with schizophrenia were widespread, encompassing more than 40% (234ml) of cerebral white matter by volume and involving all cerebral lobes. Significant increases in MD were also widespread and distributed similarly. The corpus callosum, cingulum, and thalamic radiations exhibited the most extensive pathology according to effect size. More than 50% of cortico-cortical and cortico-subcortical white matter fiber bundles comprising the connectome were disrupted in schizophrenia. Connections between hub regions comprising the rich club were disproportionately affected. Pathology did not differ between patients with schizophrenia and schizoaffective disorder and was not mediated by medication. In conclusion, although connectivity between cerebral hubs is most extensively disturbed in schizophrenia, white matter pathology is widespread, affecting all cerebral lobes and the cerebellum, leading to disruptions in the majority of the brain's fiber bundles.

Published
2021

5. 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

6. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Author

James McKay, Frank Bellivier, Mark A. Frye, Bertram Müller-Myhsok, Fermín Mayoral, I. Nicol Ferrier, Marion Leboyer, Fabian Streit, Dan J. Stein, James L. Kennedy, Christine Søholm Hansen, Scott D. Gordon, Beata Świątkowska, Valentina Escott-Price, Michael Bauer, Lina Martinsson, Donald J. MacIntyre, Oleksandr Frei, Daniel J. Smith, Sara A. Paciga, Takeo Saito, Jennifer L. Moran, Verneri Antilla, C Pantelis, Tomas Olsson, Swapnil Awasthi, Lena Backlund, Eirini Maratou, Martin Schalling, John B. Vincent, Niamh Mullins, Sarah E. Bergen, Niamh L. O'Brien, Marco P. Boks, Carsten Bøcker Pedersen, Mikael Landén, Franziska Degenhardt, Hang Zhou, Margarita Rivera, Andrew M. McIntosh, Manuel Mattheisen, Shawn Levy, Roy H. Perlis, John P. Rice, Sigurdur H. Magnusson, Amanda Dobbyn, Michael Conlon O'Donovan, Julien Bryois, Wolfgang Maier, John-Anker Zwart, J. Raymond DePaulo, Martin Alda, Laura G. Sloofman, Friederike Sophie David, James A. Knowles, Aiden Corvin, Thomas G. Schulze, Markus M. Nöthen, Nolan Kamitaki, Nina Dalkner, Brandon J. Coombes, Gustavo Turecki, Allan H. Young, Caroline M. Nievergelt, Patricia T. Michie, Ingrid Agartz, Towfique Raj, Diego Albani, Maria Grigoroiu-Serbanescu, Bernhard T. Baune, Kyooseob Ha, Vincent Millischer, Engilbert Sigurdsson, Eva C. Beins, Nicholas G. Martin, Gulja Babadjanova, Josef Frank, Eva Z. Reininghaus, Patrick F. Sullivan, Ian R. Gizer, Guy A. Rouleau, Carmel M. Loughland, Christine Lochner, Thorsten M. Kranz, Amy Perry, Arne E. Vaaler, Mariam M. Al Eissa, Simon Xi, Claire O'Donovan, Josep Antoni Ramos-Quiroga, Ketil J. Oedegaard, Helmut Vedder, Carol A. Mathews, Panagiotis Ferentinos, Tim B. Bigdeli, Derek W. Morris, Per Hoffmann, Mark Hyman Rapaport, Peter P. Zandi, Michael John Owen, Douglas M. Ruderfer, Anders D. Børglum, Catharina Lavebratt, Thorgeir E. Thorgeirsson, Paul A. Tooney, Michiaki Kubo, Steven A. Kushner, Jan Hillert, Loes M. Olde Loohuis, Anastasia Antoniou, Murielle Brum, Chikashi Terao, Nathaniel W. McGregor, Fabio Rivas, James B. Potash, Kevin S. O’Connell, Susanne Lucae, Brian M. Schilder, Katrin Gade, Stephan Ripke, Kristina Adorjan, Kari Stefansson, Tiffany A. Greenwood, Panos Roussos, Sarah Kittel-Schneider, Steven A. McCarroll, Sergi Papiol, Heon Jeong Lee, Assen Jablensky, Liliya Abramova, Dennis Hellgren, Jonas Bybjerg-Grauholm, Martin Lundberg, Hong-Hee Won, William Byerley, Lars Alfredsson, Joel Gelernter, Andrew McQuillin, Claire Slaney, Marta Ribasés, Stephanie H. Witt, Yoichiro Kamatani, Kyung Sue Hong, Marie Bækvad-Hansen, María Soler Artigas, Julie M. Cunningham, Fanny Senner, Stacy Steinberg, Paul D. Shilling, Nakao Iwata, Eystein Stordal, Armin Birner, Sarah E. Medland, Miquel Casas, Ben Michael Brumpton, Erlend Bøen, Bryan J. Mowry, Jolanta Lissowska, Francis J. McMahon, Howard J. Edenberg, Grant W. Montgomery, John I. Nurnberger, Stéphane Jamain, Claudio Toma, Ney Alliey-Rodriguez, Ole Mors, Micha Gawlik, David Curtis, Catrin Lewis, Evangelia-Eirini Tsermpini, Georgia Panagiotaropoulou, Marcella Rietschel, Jessica Yang, Ian Jones, Eduard Vieta, Ole A. Andreassen, Richard M. Myers, Dimitris Dikeos, Melissa J. Green, Janet L. Sobell, Maria Koromina, Piotr M. Czerski, Lilijana Oruc, Sven Cichon, Udo Dannlowski, Bruno Etain, Monika Budde, Alessia Fiorentino, Naomi R. Wray, Qingqin S. Li, Murray J. Cairns, Jonathan R. I. Coleman, Jose Guzman-Parra, Andreas J. Forstner, Hannah Young, Alfredo B. Cuellar-Barboza, Julian Roth, Torbjørn Elvsåshagen, Zhen Qiao, Thomas Werge, Athanassios Douzenis, Cristiana Cruceanu, Rolf Adolfsson, Peter Holmans, Vaughan J. Carr, Thomas W. Weickert, Masashi Ikeda, Joanna M. Biernacka, Lea Sirignano, Adam X. Maihofer, Ralph W. Kupka, John Strauss, Anders M. Dale, Elliot S. Gershon, Jakob Grove, Arianna Di Florio, Helena Medeiros, Ingrid Melle, Preben Bo Mortensen, Kristi Krebs, Saskia P. Hagenaars, Liz Forty, Stanley V. Catts, David M. Hougaard, Marianne Giørtz Pedersen, Andreas Reif, Toni-Kim Clarke, Anne T. Spijker, Danielle Posthuma, Manolis Kogevinas, Michael Boehnke, Rosa Bosch, Gerome Breen, Benjamin M. Neale, Jessica S. Johnson, Katherine Gordon-Smith, Cristina Sánchez-Mora, Alexander W. Charney, Henry R. Kranzler, Digby Quested, René S. Kahn, Lili Milani, Merete Nordentoft, Nathalie Brunkhorst-Kanaan, Laura M. Huckins, James T.R. Walters, Sigrid Børte, Antonio F. Pardiñas, Kristian Hveem, Julie Garnham, Jacob Lawrence, Vassily Trubetskoy, Rodney J. Scott, Nicholas Bass, Carlos N. Pato, Andrea Pfennig, Wei Xu, Calwing Liao, Nicholas John Craddock, Thomas Damm Als, Christina M. Hultman, Fernando S. Goes, Adebayo Anjorin, Evgenia Porichi, Frans Henskens, Nelson B. Freimer, Janice M. Fullerton, Cathryn M. Lewis, Srdjan Djurovic, Roel A. Ophoff, Phil Lee, Peter McGuffin, Gunnar Morken, George P. Patrinos, Alessandro Serretti, Cynthia Shannon Weickert, Pablo Cervantes, Bendik S. Winsvold, Tatiana Foroud, Tõnu Esko, Ulrich Schall, Michele T. Pato, Ji Hyun Baek, John R. Kelsoe, Olav B. Smeland, Janos Kalman, Eva C. Schulte, Joanna Hauser, Urs Heilbronner, Magnús Haraldsson, Martin Hautzinger, Lea Zillich, Eline J. Regeer, Douglas Blackwood, Laura J. Scott, Jordan W. Smoller, Michael J. Gandal, Marquis P. Vawter, Philip B. Mitchell, Ole Kristian Drange, Peter R. Schofield, Susanne Bengesser, Stefan Herms, George Kirov, Markus Leber, Louise Frisén, Thomas W. Mühleisen, Susan L. McElroy, Irwin D. Waldman, Wade H. Berrettini, Sally I. Sharp, Minsoo Kim, Lisa Jones, Eli A. Stahl, Hreinn Stefansson, Esben Agerbo, Dolores Malaspina, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Human genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), APH - Digital Health, Mullins N., Forstner A.J., O'Connell K.S., Coombes B., Coleman J.R.I., Qiao Z., Als T.D., Bigdeli T.B., Borte S., Bryois J., Charney A.W., Drange O.K., Gandal M.J., Hagenaars S.P., Ikeda M., Kamitaki N., Kim M., Krebs K., Panagiotaropoulou G., Schilder B.M., Sloofman L.G., Steinberg S., Trubetskoy V., Winsvold B.S., Won H.-H., Abramova L., Adorjan K., Agerbo E., Al Eissa M., Albani D., Alliey-Rodriguez N., Anjorin A., Antilla V., Antoniou A., Awasthi S., Baek J.H., Baekvad-Hansen M., Bass N., Bauer M., Beins E.C., Bergen S.E., Birner A., Bocker Pedersen C., Boen E., Boks M.P., Bosch R., Brum M., Brumpton B.M., Brunkhorst-Kanaan N., Budde M., Bybjerg-Grauholm J., Byerley W., Cairns M., Casas M., Cervantes P., Clarke T.-K., Cruceanu C., Cuellar-Barboza A., Cunningham J., Curtis D., Czerski P.M., Dale A.M., Dalkner N., David F.S., Degenhardt F., Djurovic S., Dobbyn A.L., Douzenis A., Elvsashagen T., Escott-Price V., Ferrier I.N., Fiorentino A., Foroud T.M., Forty L., Frank J., Frei O., Freimer N.B., Frisen L., Gade K., Garnham J., Gelernter J., Giortz Pedersen M., Gizer I.R., Gordon S.D., Gordon-Smith K., Greenwood T.A., Grove J., Guzman-Parra J., Ha K., Haraldsson M., Hautzinger M., Heilbronner U., Hellgren D., Herms S., Hoffmann P., Holmans P.A., Huckins L., Jamain S., Johnson J.S., Kalman J.L., Kamatani Y., Kennedy J.L., Kittel-Schneider S., Knowles J.A., Kogevinas M., Koromina M., Kranz T.M., Kranzler H.R., Kubo M., Kupka R., Kushner S.A., Lavebratt C., Lawrence J., Leber M., Lee H.-J., Lee P.H., Levy S.E., Lewis C., Liao C., Lucae S., Lundberg M., MacIntyre D.J., Magnusson S.H., Maier W., Maihofer A., Malaspina D., Maratou E., Martinsson L., Mattheisen M., McCarroll S.A., McGregor N.W., McGuffin P., McKay J.D., Medeiros H., Medland S.E., Millischer V., Montgomery G.W., Moran J.L., Morris D.W., Muhleisen T.W., O'Brien N., O'Donovan C., Olde Loohuis L.M., Oruc L., Papiol S., Pardinas A.F., Perry A., Pfennig A., Porichi E., Potash J.B., Quested D., Raj T., Rapaport M.H., DePaulo J.R., Regeer E.J., Rice J.P., Rivas F., Rivera M., Roth J., Roussos P., Ruderfer D.M., Sanchez-Mora C., Schulte E.C., Senner F., Sharp S., Shilling P.D., Sigurdsson E., Sirignano L., Slaney C., Smeland O.B., Smith D.J., Sobell J.L., Soholm Hansen C., Soler Artigas M., Spijker A.T., Stein D.J., Strauss J.S., Swiatkowska B., Terao C., Thorgeirsson T.E., Toma C., Tooney P., Tsermpini E.-E., Vawter M.P., Vedder H., Walters J.T.R., Witt S.H., Xi S., Xu W., Yang J.M.K., Young A.H., Young H., Zandi P.P., Zhou H., Zillich L., Adolfsson R., Agartz I., Alda M., Alfredsson L., Babadjanova G., Backlund L., Baune B.T., Bellivier F., Bengesser S., Berrettini W.H., Blackwood D.H.R., Boehnke M., Borglum A.D., Breen G., Carr V.J., Catts S., Corvin A., Craddock N., Dannlowski U., Dikeos D., Esko T., Etain B., Ferentinos P., Frye M., Fullerton J.M., Gawlik M., Gershon E.S., Goes F.S., Green M.J., Grigoroiu-Serbanescu M., Hauser J., Henskens F., Hillert J., Hong K.S., Hougaard D.M., Hultman C.M., Hveem K., Iwata N., Jablensky A.V., Jones I., Jones L.A., Kahn R.S., Kelsoe J.R., Kirov G., Landen M., Leboyer M., Lewis C.M., Li Q.S., Lissowska J., Lochner C., Loughland C., Martin N.G., Mathews C.A., Mayoral F., McElroy S.L., McIntosh A.M., McMahon F.J., Melle I., Michie P., Milani L., Mitchell P.B., Morken G., Mors O., Mortensen P.B., Mowry B., Muller-Myhsok B., Myers R.M., Neale B.M., Nievergelt C.M., Nordentoft M., Nothen M.M., O'Donovan M.C., Oedegaard K.J., Olsson T., Owen M.J., Paciga S.A., Pantelis C., Pato C., Pato M.T., Patrinos G.P., Perlis R.H., Posthuma D., Ramos-Quiroga J.A., Reif A., Reininghaus E.Z., Ribases M., Rietschel M., Ripke S., Rouleau G.A., Saito T., Schall U., Schalling M., Schofield P.R., Schulze T.G., Scott L.J., Scott R.J., Serretti A., Shannon Weickert C., Smoller J.W., Stefansson H., Stefansson K., Stordal E., Streit F., Sullivan P.F., Turecki G., Vaaler A.E., Vieta E., Vincent J.B., Waldman I.D., Weickert T.W., Werge T., Wray N.R., Zwart J.-A., Biernacka J.M., Nurnberger J.I., Cichon S., Edenberg H.J., Stahl E.A., McQuillin A., Di Florio A., Ophoff R.A., Andreassen O.A., IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Etain, Bruno

Subjects
Multifactorial Inheritance, Bipolar Disorder, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Medizin, Genome-wide association study, Major Histocompatibility Complex/genetics, Major Histocompatibility Complex, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, MESH: Bipolar Disorder, Chromosomes, Human, Spectrum disorder, Genetics, 0303 health sciences, Bipolar Disorder/genetics, MESH: Genetic Predisposition to Disease, MESH: Case-Control Studies, Phenotype, Schizophrenia, Synaptic signaling, Case-Control Studie, Human, Quantitative Trait Loci, Biology, MESH: Phenotype, MESH: Chromosomes, Human, Article, 03 medical and health sciences, MESH: Major Histocompatibility Complex, SDG 3 - Good Health and Well-being, ddc:570, medicine, Humans, Genetic Predisposition to Disease, Bipolar disorder, Multifactorial Inheritance/genetics, MESH: Genome, Human, 030304 developmental biology, MESH: Humans, Genome, Human, Risk Factor, Chromosomes, Human/genetics, Mental illness, medicine.disease, MESH: Quantitative Trait Loci, Human genetics, Psychologie, Case-Control Studies, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, MESH: Genome-Wide Association Study, Expression quantitative trait loci, MESH: Multifactorial Inheritance, Quantitative Trait Loci/genetics, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

International audience; Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

Published
2021

7. Increased power by harmonizing structural MRI site differences with the ComBat batch adjustment method in ENIGMA

Author

Raquel E. Gur, Geor Bakker, Erick J. Canales-Rodríguez, Edith Pomarol-Clotet, Cynthia Shannon Weickert, Neda Jahanshad, Ulrich Schall, Theodore D. Satterthwaite, Vince D. Calhoun, Aleix Solanes, Frans Henskens, Antonin Skoch, Sara Llufriu, Anthony A. James, Michael Stäblein, Aurora Bonvino, Kun Yang, Cyril Höschl, Christos Pantelis, Carlos López-Jaramillo, Stefan Ehrlich, S. Sarró, Stefan Kaiser, Udo Dannlowski, Fengmei Fan, Wenhao Jiang, Paul E. Rasser, Patricia T. Michie, Julian A Pineda-Zapata, Zhiren Wang, Russell T. Shinohara, Eduard Vieta, Rodney J. Scott, Tilo Kircher, Andrea Weideman, Melissa J. Green, Nicola G. Cascella, Jason M. Bruggemann, Dominik Grotegerd, Viola Oertel, Janice M. Fullerton, Theo G.M. van Erp, Stanley V. Catts, Hong Xiang, Murray J. Cairns, Jingxu Chen, Paul M. Thompson, Adrian Preda, Elisabeth Solana, Fleur M. Howells, Godfrey D. Pearlson, Anne Uhlmann, Peter Kochunov, Christian Knöchel, Fabrizio Piras, Fude Yang, Je-Yeon Yun, Yunlong Tan, Henk Temmingh, Covadonga M. Díaz-Caneja, Peter J. McKenna, Carmel M. Loughland, Alexander Tomyshev, Kang Sim, Joost Janssen, Kaleda Vg, Ruben C. Gur, Akira Sawa, Ana M. Díaz-Zuluaga, Annabella Di Giorgio, Nerisa Banaj, Jessica A. Turner, Vanessa Cropley, Gavin Cooper, Raymond Salvador, Marc L. Seal, Rhoshel K. Lenroot, Stefan S. du Plessis, Yoichiro Takayanagi, Federica Piras, Jun Soo Kwon, Dan J. Stein, Anton Albajes-Eizagirre, David C. Glahn, Vaughan J. Carr, Thomas W. Weickert, Francesca Assogna, Lydia Fortea, Joaquim Radua, Igor Nenadic, Alessandro Bertolino, Margaret D. King, Eloy Martinez-Heras, Gianfranco Spalletta, Paul A. Tooney, Tim Hahn, Hua Guo, Stefan Borgwardt, Yann Quidé, Bryan J. Mowry, Shuping Tan, Axel Krug, Therese van Amelsvoort, Elliot Hong, Irina V. Lebedeva, David Tomecek, Daniel H. Wolf, Celso Arango, Clara Alloza, Matthias Kirschner, Dana Nguyen, Kaiser, Stefan, Psychiatrie & Neuropsychologie, MUMC+: MA Med Staf Spec Psychiatrie (9), and RS: MHeNs - R2 - Mental Health

Subjects
Male, Computer science, Image Processing, Medical and Health Sciences, 0302 clinical medicine, Computer-Assisted, Image Processing, Computer-Assisted, ENIGMA Consortium collaborators, Cerebral Cortex, 05 social sciences, Brain, Middle Aged, Magnetic Resonance Imaging, 3. Good health, Mental Health, Neurology, Schizophrenia, Biomedical Imaging, Female, Algorithms, Adult, medicine.medical_specialty, Mega-analysis, Cognitive Neuroscience, Neuroimaging, SURFACE-BASED ANALYSIS, 050105 experimental psychology, Article, Cortical thickness, lcsh:RC321-571, 03 medical and health sciences, Young Adult, Physical medicine and rehabilitation, Meta-Analysis as Topic, medicine, Humans, 0501 psychology and cognitive sciences, Cortical surface, ddc:610, Gray matter, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Neurology & Neurosurgery, Volume, Psychology and Cognitive Sciences, Neurosciences, medicine.disease, Brain Disorders, Data set, 030217 neurology & neurosurgery, Diagnosis of schizophrenia
Abstract

Altres ajuts: SRB: The Australian Schizophrenia Research Bank (ASRB) was supported by the National Health and Medical Research Council of Australia (NHMRC) (Enabling Grant, ID 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation and the Schizophrenia Research Institute. Chief Investigators for ASRB were Carr, V., Schall, U., Scott, R., Jablensky, A., Mowry, B., Michie, P., Catts, S., Henskens, F., Pantelis, C. We thank Loughland, C., the ASRB Manager, and acknowledge the help of Jason Bridge for ASRB database queries. CP was supported by NHMRC Senior Principal Research Fellowships (IDs: 628386 & 1105825); GC was supported by the Schizophrenia Research Institute utilizing infrastructure funding from the New South Wales Ministry of Health and New South Wales Ministry of Trade and Investment (Australia); JMF was supported by NHMRC project grant (1063960) and the Janette Mary O'Neil Research Fellowship; MJG was supported by NHMRC as an R.D. Wright Biomedical Career Development Fellow (1061875). MJC was supported by NHMRC Senior Research Fellowship (1121474). CASSI: CSW is funded by the NSW Ministry of Health, Office of Health and Medical Research. CSW is a recipient of a National Health and Medical Research Council (Australia) Principal Research Fellowship (PRF) (#1117079). CIAM: The CIAM study (FMH - PI) was supported by the University Research Committee, University of Cape Town and South African funding bodies National Research Foundation and Medical Research Council. COBRE: The COBRE dataset and investigators were supported by NIH grants R01EB006841 & P20GM103472, as well as NSF grant 1539067. JT (senior author) and VDC are supported by 5R01MH094524. JMS is supported by R01 AA021771 and P50 AA022534. EONCKS: This work was supported by a New Partnership for Africa's Development (NEPAD) grant through the Department of Science and Technology of South Africa, the Medical Research Council of South Africa (grant number 65174). ESO: The ESO study was funded by NPU I - LO1611 and Ministry of Health, Czech Republic - Conceptual Development of Research Organization 00023001 (IKEM). FIDMAG/Project: This work was supported by the Catalan Government and several grants from the Instituto de Salud Carlos III and co-funded by European Union (ERDF/ESF, 'Investing in your future'): Miguel Servet Research Contracts and Research Project Grants. FOR2107 Marburg: The FOR2107 Marburg study was funded by the German Research Foundation (DFG), Tilo Kircher (speaker FOR2107; DFG grant numbers KI588/14-1, KI588/14-2), Axel Krug (KR 3822/5-1, KR 3822/7-2), Igor Nenadic (NE 2254/1-2), Carsten Konrad (KO 4291/3-1). FOR2107 Muenster: The FOR2107 Muenster study was funded by the German Research Foundation (DFG, grant FOR2107 DA1151/5-1 and DA1151/5-2 to UD) and the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Münster (grant Dan3/012/17 to UD). TH was supported by grants from the German Research Foundation (DFG grants HA7070/2-2, HA7070/3, HA7070/4). Frankfurt: MRI was performed at the Frankfurt Brain Imaging Center, supported by the German Research Council (DFG) and the German Ministry for Education and Research (BMBF; Brain Imaging Center Frankfurt/Main, DLR 01GO0203). GIPSI: This study was supported by Colciencias PRISMA-U.T. Huilong1 & Huilong2: This study was funded by the National Natural Science Foundation of China (81761128021; 31671145; 81401115; 81401133), Beijing Municipal Science and Technology Commission grant (Z141107002514016) and Beijing Natural Science Foundation(7162087, Beijing Municipal Administration of Hospitals Clinical medicine Development of special funding (XMLX201609; zylx201409). IGP: This study was funded by Project Grants from the Australian National Health and Medical Research Council of Australia (NHMRC; APP630471 and APP1081603), the Macquarie University's Australian Research Council Centre of Excellence in Cognition and its Disorders (CE110001021). Johns Hopkins: Supported by National Institutes of Health Grant Nos. MH-092443, MH-094268 (Silvio O. Conte Center), MH-105660, and MH-107730; foundation grants from Stanley, RUSK/S-R, and NARSAD/Brain and Behavior Research Foundation. Madrid: Supported by the Spanish Ministry of Science, Innovation and Universities, Instituto de Salud Carlos III, co-financed by ERDF Funds from the European Commission, "A way of making Europe", CIBERSAM. Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds and European Union Seventh Framework Program and H2020 Program; Fundación Familia Alonso, Fundación Alicia Koplowitz and Fundación Mutua Madrileña. MPRC1 & MPRC2: Support was received from NIH grants U01MH108148, 2R01EB015611, R01MH112180, R01DA027680, R01MH085646, P50MH103222 and T32MH067533, a State of Maryland contract (M00B6400091) and NSF grant (1620457). OLIN: The Olin study was supported by NIH grants R37MH43375 and R01MH074797. Oxford: The Oxford study MRC G0500092. SLF Rome: Support from the Italian Ministry of Health grants RC-12-13-14-15-16-17-18-19/A. RSCZ: RSCZ data collection was supported by RFBR 15-06-05758 grant. SCORE: This study was supported in part by grant 3232BO_119382 from the Swiss National Science Foundation. We thank the FePsy (Frueherkennung von Psychosen; early detection of psychosis) Study Group from the University of Basel, Department of Psychiatry, Switzerland, for the recruitment of the study participants. The FePsy Study was supported in part by grant No. SNF 3200-057216/1, ext./2, ext./3. Singapore: This study was supported by research grants from the National Healthcare Group, Singapore (SIG/05004; SIG/11003), and the Singapore Bioimaging Consortium (RP C-009/2006) research grants awarded to KS. SNUH: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (Grant no. 2013R1A2A1A03071089 and 2017M3C7A1029610). UCISZ: The UCISZ study was supported by the National Institutes of Mental Health grant number R21MH097196 to TGMvE. UCISZ data were processed by the UCI High Performance Computing cluster supported by Joseph Farran, Harry Mangalam, and Adam Brenner and the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1 TR000153. UNIBA: The UNIBA study was supported by grant funding from the Italian Ministry of Health (PE-2011-02347951). UNIMAAS: The study was supported by Dutch Organization for Health Research and Development (ZonMw 91112002) and a personal grant to Thérèse van Amelsvoort (ZonMw-VIDI: 91712394). The data was collected in a clinical trial registered in the Dutch clinical trial registry under ID: NTR5094 (http://www.trialregister.nl). UPenn: This study was supported by the National Institute of Mental Health grants MH064045, MH 60722, MH019112, MH085096 (DHW), and R01MH112847 (RTS and TDS). Zurich: This study was supported by the Swiss National Science Foundation (105314_140351 to S.K.). Matthias Kirschner acknowledges support from the National Bank Fellowship (McGill University) and the Swiss National Foundation (P2SKP3_178175). Research reported in this publication was also supported by the following National Institutes of Health grants: U54 EB020403 to PMT, R01 MH116147, U24 RR21992, R21MH097196, and TR000153 to TGMvE, S10 OD023696 and R01EB015611 to PK, T32 AG058507and 5T32 MH073526 to CRKC, R01 MH117601 to NJ, ENIGMA's NIH Big Data to Knowledge (BD2K) initiative U54 EB020403, ENIGMA Sex Differences R01MH116147, and ENIGMA-COINSTAC: Advanced World-wide Transdiagnostic Analysis of Valence System Brain Circuits R01MH121246. A common limitation of neuroimaging studies is their small sample sizes. To overcome this hurdle, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium combines neuroimaging data from many institutions worldwide. However, this introduces heterogeneity due to different scanning devices and sequences. ENIGMA projects commonly address this heterogeneity with random-effects meta-analysis or mixed-effects mega-analysis. Here we tested whether the batch adjustment method, ComBat, can further reduce site-related heterogeneity and thus increase statistical power. We conducted random-effects meta-analyses, mixed-effects mega-analyses and ComBat mega-analyses to compare cortical thickness, surface area and subcortical volumes between 2897 individuals with a diagnosis of schizophrenia and 3141 healthy controls from 33 sites. Specifically, we compared the imaging data between individuals with schizophrenia and healthy controls, covarying for age and sex. The use of ComBat substantially increased the statistical significance of the findings as compared to random-effects meta-analyses. The findings were more similar when comparing ComBat with mixed-effects mega-analysis, although ComBat still slightly increased the statistical significance. ComBat also showed increased statistical power when we repeated the analyses with fewer sites. Results were nearly identical when we applied the ComBat harmonization separately for cortical thickness, cortical surface area and subcortical volumes. Therefore, we recommend applying the ComBat function to attenuate potential effects of site in ENIGMA projects and other multi-site structural imaging work. We provide easy-to-use functions in R that work even if imaging data are partially missing in some brain regions, and they can be trained with one data set and then applied to another (a requirement for some analyses such as machine learning).

Published
2020

8. Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects

Author

Patricia T. Michie, Franziska Degenhardt, Brandon Wormley, Paola Giusti-Rodríguez, Mark J. Daly, Raquelle I. Mesholam-Gately, Ingrid Melle, Sibylle G. Schwab, Andrew McQuillin, Benjamin M. Neale, Joshua L. Roffman, Abraham Reichenberg, Pamela Sklar, Diana O. Perkins, Jennifer L. Moran, Donald W. Black, Per Hoffmann, A. Hofman, Hailiang Huang, John L. Waddington, Giulio Genovese, Aaron R. Wolen, Deborah L. Levy, David Curtis, Digby Quested, Carlos N. Pato, Nicholas John Craddock, Stephanie Williams, Kung Yee Liang, Zhouzhi Wang, Tracey L. Petryshen, Ann E. Pulver, Randy L. Buckner, Stephan Ripke, Roel A. Ophoff, Danielle Posthuma, Lili Milani, Jacques Mallet, Menachem Fromer, Christian R. Marshall, Jaana Suvisaari, Jana Strohmaier, Richard Bruggeman, Marcella Rietschel, Ayman H. Fanous, Andrew M. McIntosh, James T.R. Walters, Dimitris Dikeos, Panos Roussos, Veikko Salomaa, Aiden Corvin, Carin J. Meijer, Tiina Paunio, Assen Jablensky, Sarah E. Bergen, Nancy G. Buccola, Annelie Nordin, Wolfgang Maier, Srdjan Djurovic, Naomi R. Wray, Aniket Shetty, Joel Eriksson, Dan Rujescu, Jouko Lönnqvist, Brian Kelly, Wenting Wu, Alexander Richards, Frans Henskens, Rich Belliveau, Bryan J. Mowry, Elodie Drapeau, Andreas J. Forstner, Silviu Alin Bacanu, Jubao Duan, Tõnu Esko, Bernard Lerer, Carmel M. Loughland, Olli Pietiläinen, Michael Conlon O'Donovan, Shaun M. Purcell, Michael Gill, Thomas G. Schulze, Douglas S. Greer, Stephen W. Scherer, Eli A. Stahl, Markus M. Nöthen, Guiqing Cai, William M. Brandler, Kristin K. Nicodemus, Dominique Campion, David A. Collier, Farooq Amin, Joel N. Hirschhorn, Robin M. Murray, Timothy G. Dinan, Mark Reimers, Murray J. Cairns, Rodney J. Scott, Aarno Palotie, Robert Freedman, Nelson B. Freimer, Joshua R. Atkins, Gary Donohoe, Ann Olincy, Jonathan Sebat, Colm McDonald, Srinivas Thirumalai, John Powell, Jo Knight, Vahram Haroutunian, Dieter B. Wildenauer, Tim B. Bigdeli, Lieuwe de Haan, Peter Eichhammer, James J. Crowley, Lynn E. DeLisi, Ulrich Schall, Rolf Adolfsson, Marcelo Bertalan, Thomas Hansen, Eric Strengman, Michael Davidson, Dheeraj Malhotra, Manuel Mattheisen, Jeffrey A. Lieberman, Benedicto Crespo-Facorro, Stephanie Godard, Edward M. Scolnick, Jonathan Pimm, Bertram Müller-Myhsok, Qingqin Li, Michele T. Pato, Wiepke Cahn, Christos Pantelis, Ingrid Agartz, Brendan Bulik-Sullivan, Madhusudan Gujral, Martilias S. Farrell, Brady J. Maher, Laurent Essioux, Karin V Fuentes Fajarado, Andres Metspalu, Stephanie H. Witt, Patrick F. Sullivan, Mark Weiser, Younes Mokrab, Kai How Farh, Line Olsen, Dermot Walsh, Peter Holmans, Hugh Gurling, Joseph I. Friedman, Andrew Pocklington, Daniel P. Howrigan, Lude Franke, Tune H. Pers, Larry J. Seidman, Pablo V. Gejman, Dalila Pinto, Michael John Owen, Inez Myin-Germeys, Steven A. McCarroll, Wei Cheng, Jackie Goldstein, C. Robert Cloninger, Elliot S. Gershon, Deborah A. Nertney, Thomas Werge, Noa Carrera, Kieran C. Murphy, Rita M. Cantor, Ariel Darvasi, Mark Hansen, Annette M. Hartmann, Ole A. Andreassen, Bradley T. Webb, Henrik B. Rasmussen, David Cohen, Elvira Bramon, Erik G. Jönsson, Vaughan J. Carr, Pui Y. Lee, Masashi Ikeda, Daniele Merico, Danny Antaki, Brien P. Riley, Stefan Herms, Igor Nenadic, Bettina Konte, Kimberley D. Chambert, Jurgen Del Favero, George Kirov, Matthew C. Keller, Jacob Gratten, Douglas F. Levinson, Luba Kalaydjieva, Bhooma Thiruvahindrapuram, Alan R. Sanders, Sang-Yun Oh, Alkes L. Price, Vihra Milanova, Juha Veijola, Erik Söderman, Dragan M. Svrakic, David H. Kavanagh, Patrik K. E. Magnusson, Douglas Blackwood, Nakao Iwata, Jim van Os, Jeremy M. Silverman, Elena Parkhomenko, Kenneth L. Davis, Jing Qin Wu, Eadbhard O'Callaghan, Chris C. A. Spencer, Juha Karjalainen, Anna K. Kähler, Clement C. Zai, Nigel Williams, Joseph D. Buxbaum, Jin P. Szatkiewicz, Laura Nisenbaum, Sang Hong Lee, Yunjung Kim, Colm O'Dushlaine, René S. Kahn, Morten Mattingsdal, Inge Joa, Marian L. Hamshere, Frank Dudbridge, Ina Giegling, Sandra Meier, Derek W. Morris, Robert W. McCarley, Douglas M. Ruderfer, Paul Cormican, Lyudmila Georgieva, Sven Cichon, Josef Frank, Jianxin Shi, George N. Papadimitriou, Kenneth S. Kendler, Margot Albus, Enrico Domenici, Claudine Laurent, Francis A. O'Neill, Adam Savitz, Jordan W. Smoller, James L. Kennedy, Peter M. Visscher, Valentina Escott-Price, Christina M. Hultman, T. Scott Stroup, Elizabeth Bevilacqua, James A. Knowles, William Byerley, Paul A. Tooney, Madeline Alexander, Stanley V. Catts, David St Clair, Sophie E. Legge, Gerald Nestadt, Michelle S. Maile, Perceptual and Cognitive Neuroscience (PCN), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Stem Cell Aging Leukemia and Lymphoma (SALL), Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, MUMC+: Hersen en Zenuw Centrum (3), MUMC+: MA Psychiatrie (3), Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, APH - Mental Health, ANS - Complex Trait Genetics, Adult Psychiatry, Other departments, Marshall, Christian R, Howrigan, Daniel P, Merico, Daniele, Thiruvahindrapuram, Bhooma, Lee, S Hong, Sebat, Jonathan, Psychosis Endophenotypes International Consortium, CNV and Schizophrenia Working Groups of the Psychiatric Genomics Consortium, CNV, Schizophrenia Working Grp, Psychosis Endophenotypes, Rehabilitation Medicine, and Child and Adolescent Psychiatry / Psychology

Subjects
0301 basic medicine, Male, 16P11.2, Duplication, Autism, Rearrangement, Genome-wide association study, Copy number variant, Gene, Medical and Health Sciences, 0302 clinical medicine, DUPLICATIONS, Risk Factors, Gene duplication, Genotype, Disorder, Copy-number variation, Genetics, Genetics & Heredity, RISK, copy number variation, REARRANGEMENTS, Biological Sciences, 16p11.2, 3. Good health, Phenotype, Female, Risk, CNVS, Genetic Markers, genetic etiology, CNV and Schizophrenia Working Groups of the Psychiatric Genomics Consortium, DNA Copy Number Variations, DISORDERS, CNV, Non-allelic homologous recombination, PHENOTYPES, Biology, 03 medical and health sciences, SDG 3 - Good Health and Well-being, genomics, Journal Article, Humans, Comparative Study, Genetic Predisposition to Disease, AUTISM, Psychosis Endophenotypes International Consortium, MUTATIONS, Case-control study, Odds ratio, R1, GENE, 030104 developmental biology, genetics research, Genetic marker, Genetic Loci, Case-Control Studies, Mutation, Schizophrenia, Human medicine, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study
Abstract

Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 x 10(-15)), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 x 10(-6)). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 x 10(-11)) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 x 10(-5)). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination. Refereed/Peer-reviewed

Published
2017

9. A quantitative review of the postmortem evidence for decreased cortical N-methyl-d-aspartate receptor expression levels in schizophrenia: How can we link molecular abnormalities to mismatch negativity deficits?

Author

Vibeke S. Catts, Yan Ling Lai, Stanley V. Catts, Cyndi Shannon Weickert, and Thomas W. Weickert

Subjects
0301 basic medicine, Mismatch negativity, Receptor expression, Neuroscience(all), Gene Expression, Prefrontal Cortex, Receptors, N-Methyl-D-Aspartate, 03 medical and health sciences, Glutamatergic, 0302 clinical medicine, medicine, Animals, Humans, RNA, Messenger, Receptor, Prefrontal cortex, General Neuroscience, Glutamate receptor, NMDA receptor, medicine.disease, Meta-analysis, 030104 developmental biology, Neuropsychology and Physiological Psychology, nervous system, Schizophrenia, Models, Animal, Evoked Potentials, Auditory, Autopsy, Glutamate, Psychology, Neuroscience, 030217 neurology & neurosurgery
Abstract

Evidence suggests that anomalous mismatch negativity (MMN) in schizophrenia is related to glutamatergic abnormalities, possibly involving N-methyl-d-aspartate (NMDA) receptors. Decreased cortical expressions of NMDA receptor subunits have been observed in schizophrenia, though not consistently. To aid with integration and interpretation of previous work, we performed a meta-analysis of effect sizes of mRNA or protein levels of the obligatory NR1 subunit in prefrontal cortex from people with schizophrenia. In schizophrenia compared to unaffected controls the pooled effect size was −0.64 (95% confidence interval: −1.08 to −0.20) for NR1 mRNA reduction and −0.44 (95% confidence interval: −0.80 to −0.07) for NR1 protein reduction. These results represent the first step to a deeper understanding of the region-specific, cell-specific, and stage-specific NMDA receptor hypofunction in schizophrenia, which could be linked to mismatch negativity deficits via transgenic and pharmacological animal models.

Published
2016
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10. Endogenous testosterone levels are associated with neural activity in men with schizophrenia during facial emotion processing

Author

Cynthia Shannon Weickert, Thomas W. Weickert, Ans Vercammen, Rhoshel K. Lenroot, Raquel E. Gur, Stanley V. Catts, Christopher J. White, and Ellen Ji

Subjects
Adult, Male, medicine.medical_specialty, Inferior frontal gyrus, Endogeny, Neuropsychological Tests, behavioral disciplines and activities, Young Adult, Behavioral Neuroscience, Internal medicine, mental disorders, medicine, Humans, Testosterone, Facial emotion processing, Psychiatry, Brain Mapping, Sex Characteristics, medicine.diagnostic_test, Brain, Cognition, Testosterone (patch), Middle Aged, medicine.disease, Magnetic Resonance Imaging, Pathophysiology, Facial Expression, Oxygen, Endocrinology, Psychotic Disorders, Schizophrenia, Face, Female, Schizophrenic Psychology, Psychology, Functional magnetic resonance imaging, Facial Recognition, Photic Stimulation
Abstract

Growing evidence suggests that testosterone may play a role in the pathophysiology of schizophrenia given that testosterone has been linked to cognition and negative symptoms in schizophrenia. Here, we determine the extent to which serum testosterone levels are related to neural activity in affective processing circuitry in men with schizophrenia. Functional magnetic resonance imaging was used to measure blood-oxygen-level-dependent signal changes as 32 healthy controls and 26 people with schizophrenia performed a facial emotion identification task. Whole brain analyses were performed to determine regions of differential activity between groups during processing of angry versus non-threatening faces. A follow-up ROI analysis using a regression model in a subset of 16 healthy men and 16 men with schizophrenia was used to determine the extent to which serum testosterone levels were related to neural activity. Healthy controls displayed significantly greater activation than people with schizophrenia in the left inferior frontal gyrus (IFG). There was no significant difference in circulating testosterone levels between healthy men and men with schizophrenia. Regression analyses between activation in the IFG and circulating testosterone levels revealed a significant positive correlation in men with schizophrenia (r=.63, p=.01) and no significant relationship in healthy men. This study provides the first evidence that circulating serum testosterone levels are related to IFG activation during emotion face processing in men with schizophrenia but not in healthy men, which suggests that testosterone levels modulate neural processes relevant to facial emotion processing that may interfere with social functioning in men with schizophrenia.

Published
2015

11. Adjunctive raloxifene treatment improves attention and memory in men and women with schizophrenia

Author

Stanley V. Catts, Ruth Wells, Maryanne O'Donnell, Cherrie Galletly, Rhoshel K. Lenroot, Cynthia Shannon Weickert, Danielle Weinberg, Jayashri Kulkarni, Ryan P. Balzan, Jackie Curtis, Brooke Short, Vaughan J. Carr, Thomas W. Weickert, Ans Vercammen, D Pellen, Dennis Liu, and Peter R. Schofield

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Schizoaffective disorder, Neuropsychological Tests, Placebo, Statistics, Nonparametric, Young Adult, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Double-Blind Method, Internal medicine, medicine, Humans, Raloxifene, Longitudinal Studies, Psychiatry, Molecular Biology, Psychiatric Status Rating Scales, Memory Disorders, Sex Characteristics, Cross-Over Studies, Raloxifene Hydrochloride, Australia, Estrogen Antagonists, Middle Aged, medicine.disease, Crossover study, 3. Good health, 030227 psychiatry, Psychiatry and Mental health, Treatment Outcome, Attention Deficit Disorder with Hyperactivity, Selective estrogen receptor modulator, Schizophrenia, Adjunctive treatment, Patient Compliance, Female, Immediate Communication, Psychology, 030217 neurology & neurosurgery, medicine.drug
Abstract

There is increasing clinical and molecular evidence for the role of hormones and specifically estrogen and its receptor in schizophrenia. A selective estrogen receptor modulator, raloxifene, stimulates estrogen-like activity in brain and can improve cognition in older adults. The present study tested the extent to which adjunctive raloxifene treatment improved cognition and reduced symptoms in young to middle-age men and women with schizophrenia. Ninety-eight patients with a diagnosis of schizophrenia or schizoaffective disorder were recruited into a dual-site, thirteen-week, randomized, double-blind, placebo-controlled, crossover trial of adjunctive raloxifene treatment in addition to their usual antipsychotic medications. Symptom severity and cognition in the domains of working memory, attention/processing speed, language and verbal memory were assessed at baseline, 6 and 13 weeks. Analyses of the initial 6-week phase of the study using a parallel groups design (with 39 patients receiving placebo and 40 receiving raloxifene) revealed that participants receiving adjunctive raloxifene treatment showed significant improvement relative to placebo in memory and attention/processing speed. There was no reduction in symptom severity with treatment compared with placebo. There were significant carryover effects, suggesting some cognitive benefits are sustained even after raloxifene withdrawal. Analysis of the 13-week crossover data revealed significant improvement with raloxifene only in attention/processing speed. This is the first study to show that daily, oral adjunctive raloxifene treatment at 120 mg per day has beneficial effects on attention/processing speed and memory for both men and women with schizophrenia. Thus, raloxifene may be useful as an adjunctive treatment for cognitive deficits associated with schizophrenia.

Published
2015

12. Modeling Linkage Disequilibrium Increases Accuracy of Polygenic Risk Scores

Author

Bjarni J. Vilhjálmsson, Jian Yang, Hilary K. Finucane, Alexander Gusev, Sara Lindström, Stephan Ripke, Giulio Genovese, Po-Ru Loh, Gaurav Bhatia, Ron Do, Tristan Hayeck, Hong-Hee Won, Sekar Kathiresan, Michele Pato, Carlos Pato, Rulla Tamimi, Eli Stahl, Noah Zaitlen, Bogdan Pasaniuc, Gillian Belbin, Eimear E. Kenny, Mikkel H. Schierup, Philip De Jager, Nikolaos A. Patsopoulos, Steve McCarroll, Mark Daly, Shaun Purcell, Daniel Chasman, Benjamin Neale, Michael Goddard, Peter M. Visscher, Peter Kraft, Nick Patterson, Alkes L. Price, 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, 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, Franziska Degenhardt, Jurgen Del Favero, Lynn E. DeLisi, 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, Lyudmila Georgieva, Elliot S. Gershon, Ina Giegling, Paola Giusti-Rodrguez, Stephanie Godard, Jacqueline I. Goldstein, Vera Golimbet, Srihari Gopal, Jacob Gratten, Jakob Grove, 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 Julia, Rene S. Kahn, Luba Kalaydjieva, Sena Karachanak-Yankova, Juha Karjalainen, David Kavanagh, Matthew C. Keller, Brian J. Kelly, James L. Kennedy, Andrey Khrunin, Yunjung Kim, Janis Klovins, James A. Knowles, Bettina Konte, Vaidutis Kucinskas, Zita Ausrele Kucinskiene, Hana Kuzelova-Ptackova, Anna K. Kahler, 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 Lnnqvist, 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, Preben B. Mortensen, Kieran C. Murphy, Robin M. Murray, Inez Myin-Germeys, Bertram Mller-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 Pietilinen, 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 Sderman, Srinivas Thirumalai, Draga Toncheva, Paul A. Tooney, 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, Jing Qin Wu, Hualin Simon Xi, Clement C. Zai, Xuebin Zheng, Fritz Zimprich, Naomi R. Wray, Kari Stefansson, 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, Tonu Esko, Pablo V. Gejman, Michael Gill, Hugh Gurling, Christina M. Hultman, Nakao Iwata, Assen V. Jablensky, Erik G. Jonsson, 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, Bryan J. Mowry, Markus M. Nthen, 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, David J. Hunter, Muriel Adank, Habibul Ahsan, Kristiina Aittomäki, Laura Baglietto, Sonja Berndt, Carl Blomquist, Federico Canzian, Jenny Chang-Claude, Stephen J. Chanock, Laura Crisponi, Kamila Czene, Norbert Dahmen, Isabel dos Santos Silva, Douglas Easton, A. Heather Eliassen, Jonine Figueroa, Olivia Fletcher, Montserrat Garcia-Closas, Mia M. Gaudet, Lorna Gibson, Christopher A. Haiman, Per Hall, Aditi Hazra, Rebecca Hein, Brian E. Henderson, Albert Hofman, John L. Hopper, Astrid Irwanto, Mattias Johansson, Rudolf Kaaks, Muhammad G. Kibriya, Peter Lichtner, Eiliv Lund, Enes Makalic, Alfons Meindl, Hanne Meijers-Heijboer, Bertram Müller-Myhsok, Taru A. Muranen, Heli Nevanlinna, Petra H. Peeters, Julian Peto, Ross L. Prentice, Nazneen Rahman, María José Sánchez, Daniel F. Schmidt, Rita K. Schmutzler, Melissa C. Southey, Ruth Travis, Clare Turnbull, Andre G. Uitterlinden, Rob B. van der Luijt, Quinten Waisfisz, Zhaoming Wang, Alice S. Whittemore, Rose Yang, Wei Zheng, ANS - Amsterdam Neuroscience, Adult Psychiatry, Other departments, CCA -Cancer Center Amsterdam, ARD - Amsterdam Reproduction and Development, Human Genetics, Grove, Jakob, Complex Trait Genetics, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Vilhjalmsson, Bjarni J, Yang, Jian, Finucane, Hilary K, Gusev, Alexander, Lee, SH, Price, Alkes L, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) study, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Study, Psychosis Endophenotype International Consortium, Wellcome Trust Case Control Consortium, Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON), Human genetics, NCA - Brain mechanisms in health and disease, CCA - Oncogenesis, CCA - Quality of life, CCA - Cancer biology and immunology, Psychiatry, Department of Technology and Operations Management, Department of Organisation and Personnel Management, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Cell biology, and Internal Medicine

Subjects
Multifactorial Inheritance, Linkage disequilibrium, Complex disease, heritability, Bioinformatics, Medical and Health Sciences, Linkage Disequilibrium, 0302 clinical medicine, Theoretical, External reference, Models, Statistics, GWAS, Genetics(clinical), Genetics (clinical), Mathematics, Genetics & Heredity, Schizophrenia Working Group of the Psychiatric Genomics Consortium, 0303 health sciences, Single Nucleotide, Biological Sciences, Serious Mental Illness, Prognosis, Thresholding, Regression, Mental Health, Phenotype, polygenic risk scores, Mixed model, Multiple Sclerosis, Genotype, Quantitative Trait Loci, polygenic risk score, schizophrenia, GWAS, Discovery, Quantitative trait locus, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genetics, Humans, p-value, Pruning (decision trees), Polymorphism, Genome-Wide Association Study, Schizophrenia, Models, Theoretical, 030304 developmental biology, genome-wide association study, and Risk of Inherited Variants in Breast Cancer (DRIVE) study, Brain Disorders, Data set, schizophrenia, Sample size determination, polygenic risk score, Polygenic risk score, 030217 neurology & neurosurgery, linkage disequilibrium
Abstract

Polygenic risk scores have shown great promise in predicting complex disease risk and will become more accurate as training sample sizes increase. The standard approach for calculating risk scores involves linkage disequilibrium (LD)-based marker pruning and applying a p value threshold to association statistics, but this discards information and can reduce predictive accuracy. We introduce LDpred, a method that infers the posterior mean effect size of each marker by using a prior on effect sizes and LD information from an external reference panel. Theory and simulations show that LDpred outperforms the approach of pruning followed by thresholding, particularly at large sample sizes. Accordingly, predicted R-2 increased from 20.1% to 25.3% in a large schizophrenia dataset and from 9.8% to 12.0% in a large multiple sclerosis dataset. A similar relative improvement in accuracy was observed for three additional large disease datasets and for non-European schizophrenia samples. The advantage of LDpred over existing methods will grow as sample sizes increase. Refereed/Peer-reviewed

Published
2015

13. Estimation of Genetic Correlation via Linkage Disequilibrium Score Regression and Genomic Restricted Maximum Likelihood

Author

Guiyan Ni, Gerhard Moser, Naomi R. Wray, S. Hong Lee, 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, 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, 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 Juliá, 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 Chee Keong, 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 Mattingsda, 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 Olinc, Line Olsen, Jim Van Os, Christos Pantelis, George N. Papadimitriou, Sergi Papio, Elena Parkhomenko, Michele T. Pato, Tiina Paunio, Milica Pejovic-Milovancevic, Diana O. Perkins, Olli Pietiläinenl, 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. Stah, 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, 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. McCarrol, 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 Rietsche, 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, APH - Mental Health, ANS - Complex Trait Genetics, Adult Psychiatry, Ni, Guiyan, Moser, Gerhard, Wray, Naomi R, Lee, S Hong, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Clinicum, Department of Psychiatry, and HUS Psychiatry

Subjects
0301 basic medicine, Linkage disequilibrium, Schizophrenia/genetics, INFORMATION, Restricted maximum likelihood, Inheritance Patterns, linkage disequilibrium score regression, Bioinformatics, Medical and Health Sciences, 3124 Neurology and psychiatry, Linkage Disequilibrium, biasedness, 0302 clinical medicine, Statistics, Databases, Genetic, WIDE ASSOCIATION, Genetics(clinical), PARTITIONING HERITABILITY, Genetics (clinical), Genetics & Heredity, education.field_of_study, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Likelihood Functions, Genome, Body Height/genetics, accuracy, Regression analysis, Single Nucleotide, Biological Sciences, Polymorphism, Single Nucleotide/genetics, genetic correlation, Regression, STATISTICS, genomic restricted maximum likelihood, Mental Health, Phenotype, Regression Analysis, COMPLEX HUMAN TRAITS, Single Nucleotide/genetics, Human, Adult, SUSCEPTIBILITY LOCI, Genotype, SNP heritability, body mass index, genome-wide SNPs, height, schizophrenia, Population, Haplotypes/genetics, Biology, Genetic correlation, Polymorphism, Single Nucleotide, 03 medical and health sciences, Databases, Genetic, ddc:570, Report, Genetics, Humans, Linkage Disequilibrium/genetics, Computer Simulation, Polymorphism, education, linkage disequilibrium score regression (LDSC), Genome, Human, Human Genome, genetic architecture, Genetic architecture, Body Height, Brain Disorders, Inheritance Patterns/genetics, BODY-MASS INDEX, 030104 developmental biology, Haplotypes, Sample size determination, Schizophrenia, 3111 Biomedicine, HUMAN HEIGHT, 030217 neurology & neurosurgery
Abstract

J. Lönnqvist on työryhmän Psychiat Genomics Consortium jäsen. Genetic correlation is a key population parameter that describes the shared genetic architecture of complex traits and diseases. It can be estimated by current state-of-art methods, i.e., linkage disequilibrium score regression (LDSC) and genomic restricted maximum likelihood (GREML). The massively reduced computing burden of LDSC compared to GREML makes it an attractive tool, although the accuracy (i.e., magnitude of standard errors) of LDSC estimates has not been thoroughly studied. In simulation, we show that the accuracy of GREML is generally higher than that of LDSC. When there is genetic heterogeneity between the actual sample and reference data from which LD scores are estimated, the accuracy of LDSC decreases further. In real data analyses estimating the genetic correlation between schizophrenia (SCZ) and body mass index, we show that GREML estimates based on similar to 150,000 individuals give a higher accuracy than LDSC estimates based on similar to 400,000 individuals (from combinedmeta-data). A GREML genomic partitioning analysis reveals that the genetic correlation between SCZ and height is significantly negative for regulatory regions, which whole genome or LDSC approach has less power to detect. We conclude that LDSC estimates should be carefully interpreted as there can be uncertainty about homogeneity among combined meta-datasets. We suggest that any interesting findings from massive LDSC analysis for a large number of complex traits should be followed up, where possible, with more detailed analyses with GREML methods, even if sample sizes are lesser.

Published
2017

14. Age at first birth in women is genetically associated with increased risk of schizophrenia

Author

Fritz Zimprich, Manuel Mattheisen, Edward M. Scolnick, Ayman H. Fanous, Henrik B. Rasmussen, Steven A. McCarroll, Ingrid Agartz, Carmel M. Loughland, Aiden Corvin, Ann Olincy, Anders D. Børglum, F. Anthony O'Neill, T. Scott Stroup, Elizabeth Bevilacqua, Sandra Meier, Ulrich Schall, Jouko Lönnqvist, Jianxin Shi, C. Robert Cloninger, Judit Bene, Veikko Salomaa, George N. Papadimitriou, Milica Pejovic-Milovancevic, Béla Melegh, Kari Stefansson, Brendan Bulik-Sullivan, Janis Klovins, Enrico Domenici, Sibylle G. Schwab, Dai Wang, Assen Jablensky, Mari Nelis, Sang Yun Oh, Peter Holmans, Aaron R. Wolen, Hualin Simon Xi, Eric Strengman, Bryan J. Mowry, Michael Gill, Kung Yee Liang, William Byerley, Rolf Adolfsson, Hugh Gurling, Joseph I. Friedman, Andrew Pocklington, Brien P. Riley, Engilbert Sigurdsson, Benjamin M. Neale, Miaoxin Li, Michael Davidson, Bernard Lerer, Michele T. Pato, Xuebin Zheng, Patrick F. Sullivan, Frans Henskens, Madeline Alexander, Andrew M. McIntosh, Inez Myin-Germeys, Draga Toncheva, Liene Nikitina-Zake, Kenneth S. Kendler, Carin J. Meijer, Robin M. Murray, Richard E. Straub, Ann E. Pulver, Menachem Fromer, Derek W. Morris, Douglas M. Ruderfer, Mythily Subramaniam, Paul Cormican, Lyudmila Georgieva, Giulio Genovese, Brion S. Maher, Stanley V. Catts, David St Clair, Robert W. McCarley, David Cohen, Nancy G. Buccola, Dan Rujescu, Carlos N. Pato, Kristin K. Nicodemus, Josef Frank, Claudine Laurent, Dominique Campion, Guiyan Ni, James L. Kennedy, Sena Karachanak-Yankova, Nicholas John Craddock, Peter M. Visscher, Valentina Escott-Price, Jeffrey A. Lieberman, Deborah A. Nertney, Bertram Müller-Myhsok, Marcella Rietschel, Dimitris Dikeos, Stephanie Godard, Stephanie Williams, Andres Metspalu, John L. Waddington, Sophie E. Legge, Roel A. Ophoff, Jonathan Pimm, Richard Bruggeman, Tim B. Bigdeli, Gerald Nestadt, Mark Weiser, Kieran C. Murphy, Eric F.C. Cheung, Kang Sim, Jordan W. Smoller, David J. Kavanagh, Inge Joa, Jens R. Wendland, Thomas G. Schulze, Richard A. Belliveau, Sarah E. Bergen, Ditte Demontis, David Curtis, Todd Lencz, Danielle Posthuma, René S. Kahn, Lili Milani, Randy L. Buckner, Jianjun Liu, Petr Slominsky, Wiepke Cahn, Hana Kuzelova-Ptackova, Sergi Papiol, Tune H. Pers, Stephan Ripke, Rita M. Cantor, Ariel Darvasi, Christina M. Hultman, Larry J. Seidman, Eli A. Stahl, David A. Collier, Michael Conlon O'Donovan, Svetlana A. Limborska, James T.R. Walters, Farooq Amin, Noa Carrera, Ronald Y.L. Chen, Pablo V. Gejman, Joel N. Hirschhorn, Zita Ausrele Kucinskiene, Michael John Owen, Ina Giegling, Stephanie H. Witt, Timothy G. Dinan, Margot Albus, Wei Cheng, Marian L. Hamshere, Markus M. Nöthen, Thomas Werge, Guiqing Cai, Raquelle I. Mesholam-Gately, Annette M. Hartmann, Ingrid Melle, Ole A. Andreassen, Preben Bo Mortensen, Hannelore Ehrenreich, Tiina Paunio, James A. Knowles, Pak C. Sham, Marion Friedl, Teimuraz Silagadze, Dermot Walsh, Emily H. M. Wong, Igor Nenadic, Matthew C. Keller, John Powell, Naomi R. Wray, Patricia T. Michie, Bradley T. Webb, Lude Franke, Mark Hansen, Masashi Ikeda, Sven Cichon, Elvira Bramon, Frank Dudbridge, Erik G. Jönsson, Annelie Nordin, Wolfgang Maier, Peter Eichhammer, Christian R. Schubert, J. Mallet, Jacob Gratten, Andrey Khrunin, Jacqueline I. Goldstein, Panos Roussos, Pamela Sklar, Diana O. Perkins, Srdjan Djurovic, Phil Lee, Elodie Drapeau, Douglas F. Levinson, Nadine Cohen, Luba Kalaydjieva, Brandon Wormley, Tao Li, Tõnu Esko, Alexander Richards, Srihari Gopal, Jubao Duan, Anil K. Malhotra, Elisabeth Stögmann, Gary Donohoe, Kimberly Chambert, Sara Marsal, Hreinn Stefansson, Jo Knight, Ole Mors, Per Hoffmann, Dieter B. Wildenauer, James J. Crowley, Srinivas Thirumalai, Vahram Haroutunian, A. Hofman, Hailiang Huang, Thomas Hansen, Daniel R. Weinberger, Andrew McQuillin, Vaughan J. Carr, Vaidutis Kučinskas, Jimmy Lee Chee Keong, Digby Quested, Aarno Palotie, Robert Freedman, Hon-Cheong So, Jennifer L. Moran, Donald W. Black, Mark Reimers, Abraham Reichenberg, Jurgen Del Favero, Paola Giusti-Rodríguez, Tracey L. Petryshen, Olli Pietiläinen, Franziska Degenhardt, Laurent Essioux, Esben Agerbo, Qiang Wang, Jana Strohmaier, Siow Ann Chong, Johan G. Eriksson, Martin Begemann, Younes Mokrab, Colm McDonald, Silviu Alin Bacanu, Martilias S. Farrell, Christos Pantelis, Kai How Farh, Line Olsen, Naser Durmishi, Antonio Julià, Stefan Herms, Qingqin S. Li, Bettina Konte, George Kirov, Rodney J. Scott, Nelson B. Freimer, Mads V. Hollegaard, Shaun Purcell, Erik Söderman, Dragan M. Svrakic, Patrik K. E. Magnusson, Douglas Blackwood, Jin P. Szatkiewicz, Sang Hong Lee, Yunjung Kim, Colm O'Dushlaine, Morten Mattingsdal, Jim van Os, Sarah Tosato, Milan Macek, Joshua L. Roffman, Jan Lubinski, Eadbhard O'Callaghan, Juha Karjalainen, Vera Golimbet, Anna K. Kähler, Clement C. Zai, Nigel Williams, Joseph D. Buxbaum, Laura Nisenbaum, Eric Y.H. Chen, David M. Hougaard, Jaana Suvisaari, Chris C. A. Spencer, Alan R. Sanders, Alkes L. Price, Vihra Milanova, Juha Veijola, Christian Hammer, Raymond C.K. Chan, Stacy Steinberg, Nakao Iwata, Jeremy M. Silverman, Mark J. Daly, Elena Parkhomenko, Kenneth L. Davis, Lieuwe de Haan, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), Kučinskas, Vaidutis, Kučinskienė, Zita Aušrelė, Ni, Guiyan, Gratten, Jacob, Wray, Naomi R, Lee, Sang Hong, Germeys, Inez, Complex Trait Genetics, Háskóli Íslands, University of Iceland, Child and Adolescent Psychiatry / Psychology, Research Programs Unit, Diabetes and Obesity Research Program, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, University Management, Department of Psychiatry, Center for Population, Health and Society, Department of Public Health, Centre of Excellence in Complex Disease Genetics, Research Programme of Molecular Medicine, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, and Genomics of Neurological and Neuropsychiatric Disorders

Subjects
0301 basic medicine, Multifactorial Inheritance, PATERNAL-AGE, 3124 Neurology and psychiatry, COMMON SNPS, fluids and secretions, 0302 clinical medicine, CHILD, Risk Factors, Pregnancy, 2.1 Biological and endogenous factors, Medicine, Aetiology, Pediatric, PROPORTION, Schizophrenia Working Group of the Psychiatric Genomics Consortium, 0303 health sciences, Multidisciplinary, PSYCHIATRIC-DISORDERS, BIPOLAR DISORDER, Biobank, 3. Good health, AFB, Mental Health, Schizophrenia, Female, Erfðarannsóknir, Psychosocial, TRAITS, schizophrenia, age at birth, AFB, Maternal Age, Adult, age at first birth in women, genetic association, Offspring, Science, Genetic correlation, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Geðklofi, Genetics, age at birth, Humans, Genetic Predisposition to Disease, Bipolar disorder, General, Biology, Genetic association study, 030304 developmental biology, Genetic association, business.industry, Genetic heterogeneity, Prevention, average aged parents, Parturition, SCORE REGRESSION, bacterial infections and mycoses, medicine.disease, Mental health, Brain Disorders, respiratory tract diseases, schizophrenia, Good Health and Well Being, 030104 developmental biology, younger and older parents, DE-NOVO MUTATIONS, ddc:000, Human medicine, business, 030217 neurology & neurosurgery, Demography
Abstract

Publisher's version (útgefin grein), Previous studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is −0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health., This research is supported by the Australian National Health and Medical Research Council (1080157, 1087889, 1103418, 1127440), and the Australian Research Council (DP160102126, FT160100229). This research has been conducted using the UK Biobank Resource. UK Biobank (http://www.ukbiobank.ac.uk) Research Ethics Committee (REC) approval number is 11/NW/0382. Our reference number approved by UK Biobank is 14575.

Published
2017

15. Reducing long-term antipsychotic use: a therapeutic dead end?

Author

Stanley V. Catts and Brian I. O'Toole

Subjects
medicine.medical_specialty, Psychotherapist, business.industry, Schizophrenia (object-oriented programming), medicine.medical_treatment, MEDLINE, behavioral disciplines and activities, 030227 psychiatry, Term (time), 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Clinical evidence, Dead end, mental disorders, medicine, Schizophrenia, Humans, Antipsychotic, business, Psychiatry, 030217 neurology & neurosurgery, Antipsychotic Agents
Abstract

Murray and colleagues' confident advice[1][1] to psychiatrists, encouraging them to leave fewer patients with schizophrenia on long-term medication, is based on one of several possible interpretations of a selected literature, and little clinical evidence. We consider that at times Murray and

Published
2017

16. Raising the standard of care in the treatment of schizophrenia: Yes we can!

Author

Brian I. O'Toole and Stanley V. Catts

Subjects
Decision making capacity, Psychiatry, medicine.medical_specialty, Standard of care, Psychotherapist, business.industry, Schizophrenia (object-oriented programming), Standard of Care, General Medicine, Raising (linguistics), 030227 psychiatry, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Cardiovascular Diseases, Schizophrenia, Medicine, Humans, 030212 general & internal medicine, business, Antipsychotic Agents
Abstract

Objective: In response to evidence of deteriorating outcomes of people with schizophrenia we recently published a critical review in the journal concerning why outcomes for schizophrenia are not improving. A published commentary on our review raised criticisms that we aim to address herein. Method: Published data related to four issues raised in the commentary were reviewed. Results: There is a body of evidence that supports the possibility of dramatic improvements in treatment effectiveness, presented in our critical review, and these can be achieved within existing financial resources and present day understanding of the pathophysiology of schizophrenia. However, the commentary leads us to highlight four current obstacles to improving treatment effectiveness: (1) the belief of many psychiatrists that long-term antipsychotic medication raises the cardiovascular mortality rate in schizophrenia when the opposite is almost certainly the case; (2) the need to improve psychiatrist training in diagnostic and communication skills, especially with first episode presentations; (3) the requirement for comprehensive and structured assessment of the highly prevalent deficits in insight and decision making capacity associated with schizophrenia; and (4) the need for improved intervention design to minimise the impact of these deficits on treatment choice and refusal. Conclusion: With a sense of professional urgency, a genuinely respectful and caring partnership between clinicians, affected individuals and their families, and researchers, with relative little innovation, we conclude that the standard of care can definitely be raised now in the treatment of schizophrenia.

Published
2017

17. Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

Author

Cristina Cereda, Jurjen J. Luykx, Sandra Meier, Derek W. Morris, Douglas M. Ruderfer, Mythily Subramaniam, Paul Cormican, Lyudmila Georgieva, John Landers, Silvana Penco, Marian L. Hamshere, Frank Dudbridge, Mari Nelis, Dick Schijven, Jimmy Lee, Sarah E. Bergen, Alessandro Padovani, Nicholas W. Wood, Meraida Polak, Hannelore Ehrenreich, Nancy G. Buccola, Noa Carrera, Stefan Herms, Panos Roussos, Marion Friedl, Teimuraz Silagadze, Jim van Os, Annette M. Hartmann, Ole A. Andreassen, R. Jeroen Pasterkamp, Sibylle G. Schwab, Aleksey Shatunov, Eli A. Stahl, David A. Collier, Farooq Amin, Michael Conlon O'Donovan, Guiqing Cai, Kung-Yee Liang, Denis C. Bauer, Charles Curtis, Brion S. Maher, Ashley R. Jones, Sara L. Pulit, Sarah Tosato, Milan Macek, Vivianna M. Van Deerlin, Vincenzo Silani, Pietro Fratta, Bettina Konte, Rosanna Tortelli, Dan Rujescu, T. Scott Stroup, Elizabeth Bevilacqua, Christian Lunetta, Bradley T. Webb, Christophe Tzourio, Patrick Vourc'h, Joel N. Hirschhorn, Gilbert Bensimon, Timothy G. Dinan, Thomas G. Schulze, Richard A. Belliveau, Daniel R. Weinberger, Andrew McQuillin, Qingqin S. Li, Orla Hardiman, Claudine Laurent, Masashi Ikeda, Tim Kahlke, Rodney J. Scott, Frans Henskens, Tune H. Pers, Wolfgang Lieb, Christian Hammer, Elvira Bramon, Hana Kuzelova-Ptackova, Raquelle I. Mesholam-Gately, Ingrid Melle, Nadine Cohen, David Cohen, Nazli Basak, Elisabeth Stögmann, Nelson B. Freimer, Peter Eichhammer, J. Mallet, Preben Bo Mortensen, Robert H. Brown, Wouter van Rheenen, Roberto Del Bo, Dai Wang, Laurent Essioux, Larry J. Seidman, Hreinn Stefansson, Erik G. Jönsson, Mads V. Hollegaard, Raymond C.K. Chan, Susana Pinto, Alexander Richards, Jubao Duan, Peter Holmans, George Kirov, Pablo V. Gejman, Philippe Amouyel, Stephanie Godard, Dieter B. Wildenauer, Martina Wiedau-Pazos, Stacy Steinberg, Ole Mors, Andres Metspalu, Rolf Adolfsson, Shaun Purcell, Hugh Gurling, Joseph I. Friedman, Erik Söderman, Mark Weiser, Giacomo P. Comi, James A. Knowles, Peter M. Andersen, Brien P. Riley, Nakao Iwata, Jeremy M. Silverman, Mark J. Daly, Elena Parkhomenko, Digby Quested, Srinivas Thirumalai, Ulrich Schall, Jan Lubinski, Dragan M. Svrakic, Aaron R. Wolen, S. Hong Lee, Andrew Pocklington, Bernard Lerer, Vahram Haroutunian, Matthew C. Kiernan, Kenneth L. Davis, Assen Jablensky, William Byerley, Karol Estrada, Aarno Palotie, Cinzia Tiloca, Eadbhard O'Callaghan, Perry T.C. van Doormaal, Colm McDonald, Federico Casale, Thomas Meitinger, Robert Freedman, Gerome Breen, Milena Blagojevic-Radivojkov, Ian P. Blair, Ann E. Pulver, Jan H. Veldink, Giancarlo Logroscino, Miaoxin Li, Abraham Reichenberg, Esben Agerbo, Siddharthan Chandran, Patrik K. E. Magnusson, Andrew M. McIntosh, Gianni Sorarù, Maura Brunetti, Xuebin Zheng, Madeline Alexander, James L. Kennedy, Douglas Blackwood, Menachem Fromer, Martilias S. Farrell, Alan R. Sanders, Dominic B. Rowe, Alexis Brice, Jonathan Pimm, Emily H. M. Wong, Jana Strohmaier, André G. Uitterlinden, Andrea Calvo, Carsten Drepper, John Q. Trojanowski, Marcella Rietschel, Siow Ann Chong, Karen E. Morrison, Sang-Yun Oh, Laura Nisenbaum, Margaret O'Brien, Alkes L. Price, Carin J. Meijer, Michael Davidson, John Powell, Petr Slominsky, Wiepke Cahn, Cinzia Gellera, Vihra Milanova, Peter M. Visscher, Patricia T. Michie, Dimitris Dikeos, Jianxin Shi, Veikko Salomaa, Philip Van Damme, James J. Crowley, Younes Mokrab, Valentina Escott-Price, Jesus S. Mora, Stanley V. Catts, David St Clair, Bernhard Landwehrmeyer, John Hardy, Kristin K. Nicodemus, Dominique Campion, Juha Veijola, Wim Robberecht, Thomas Meyer, Peter Lichtner, Christos Pantelis, Markus Weber, Nilo Riva, Jin P. Szatkiewicz, Michele T. Pato, Cinzia Bertolin, Frank P. Diekstra, Simon Arcuti, Bryan J. Mowry, Hon-Cheong So, Adriano Chiò, Viviana Pensato, Yunjung Kim, Jean-François Dartigues, Zita Ausrele Kucinskiene, Inez Myin-Germeys, Jaana Suvisaari, Sophie E. Legge, Roel A. Ophoff, Philippe Corcia, Gerald Nestadt, Stephan Ripke, Kuang Lin, Paola Giusti-Rodríguez, Michael John Owen, Chris C. A. Spencer, Safa Saker-Delye, Robert W. McCarley, Kimberley D. Chambert, Brandon Wormley, Isabella Fogh, Mamede de Carvalho, Pamela J. Shaw, Tõnu Esko, Ronald Y. L. Chan, Jianjun Liu, Tim B. Bigdeli, Christian R. Andres, David M. Hougaard, Michael Gill, Ammar Al-Chalabi, Colm O'Dushlaine, Rick A.A. van der Spek, Gary Donohoe, Tao Li, Jonathan D. Glass, Christopher Shaw, Draga Toncheva, Leonard H. van den Berg, Liene Nikitina-Zake, Morten Mattingsdal, François Salachas, Andrey Khrunin, Line Olsen, Jochen H. Weishaupt, Jo Knight, Katie Sidle, Filip Eftimov, Massimiliano Filosto, Russell L. McLaughlin, Pak C. Sham, Joshua L. Roffman, Thomas Hansen, Naser Durmishi, Deborah A. Nertney, Juha Karjalainen, Robert Swingler, Ditte Demontis, Vaidutis Kučinskas, Jennifer L. Moran, Leo McCluskey, Donald W. Black, Eric F.C. Cheung, Qiang Wang, Olli Pietilainen, Vera Golimbet, Anna K. Kähler, Clement C. Zai, Nigel Williams, Annelie Nordin, Wolfgang Maier, Bradley N. Smith, Ettore Beghi, Rosa Capozzo, Garth A. Nicholson, Markus M. Nöuthen, Jordan W. Smoller, Eric Y.H. Chen, Joseph D. Buxbaum, Letizia Mazzini, Andrea Malaspina, Antonio Julià, Stephanie Williams, Tracey L. Petryshen, Christine Payan, Johan G. Eriksson, Carmel M. Loughland, Elodie Drapeau, Lieuwe de Haan, Martin Begemann, Lukas Tittmann, Franziska Degenhardt, Mark Reimers, Jurgen Del Favero, Jacqueline I. Goldstein, Annelot M. Dekker, Sergi Papiol, Svetlana A. Limborska, René S. Kahn, Shuna Colville, Kelly L. Williams, Pamela Sklar, Diana O. Perkins, Lili Milani, Ayman H. Fanous, Nicola Ticozzi, Fernando Rivadeneira, Marianne de Visser, P. Nigel Leigh, James T.R. Walters, Josef Frank, Aiden Corvin, Silviu Alin Bacanu, John L. Waddington, Stephanie H. Witt, Tiina Paunio, Margot Albus, Catherine Lomen-Hoerth, Sara Marsal, Per Hoffmann, David Curtis, Cindy Maurel, Todd Lencz, Orietta Pansarasa, Manuel Mattheisen, Anneke J. van der Kooi, A. Hofman, Dermot Walsh, Hailiang Huang, Ann Olincy, Anders D. Børglum, Ricardo Rojas-García, William Sproviero, Albert C. Ludolph, Edward M. Scolnick, Danielle Posthuma, George N. Papadimitriou, Michael A. van Es, Fritz Zimprich, F. Anthony O'Neill, Lude Franke, Jouko Lönnqvist, Daniel G. Bradley, Sven Cichon, Susanna Abdulla, Kristel R. van Eijk, Ingrid Agartz, Elisabetta Pupillo, Milica Pejovic-Milovancevic, Antonia Ratti, Henrik B. Rasmussen, Kari Stefansson, Brendan Bulik-Sullivan, Béla Melegh, Stéphanie Millecamps, Janis Klovins, Enrico Domenici, Michael Sendtner, Kai-How Farh, Randy L. Buckner, Albert Hofman, Benjamin M. Neale, Naomi R. Wray, An Goris, Kang Sim, Lauren Elman, Giulio Genovese, Jens R. Wendland, Rita M. Cantor, Ariel Darvasi, Christina M. Hultman, Sandra D'Alfonso, Cristina Moglia, Carlos N. Pato, Sena Karachanak-Yankova, Nicholas John Craddock, Richard W. Orrell, Richard Bruggeman, Kenneth S. Kendler, Alan M. Pittman, Robin M. Murray, Richard E. Straub, Cathryn M. Lewis, Srdjan Djurovic, Vincent Meininger, Jeffrey A. Lieberman, Bertram Müller-Myhsok, Phil Lee, David J. Kavanagh, Srihari Gopal, Igor Nenadic, Matthew C. Keller, Christian R. Schubert, Jacob Gratten, Alexandra Durr, Roger Pamphlett, Douglas F. Levinson, Luba Kalaydjieva, Chiara Zecca, Anil K. Malhotra, Andre Franke, Vaughan J. Carr, Steven A. McCarroll, C. Robert Cloninger, Judit Bene, Ina Giegling, Wei Cheng, Hualin Simon Xi, Thomas Werge, Eric Strengman, Susanne Petri, Engilbert Sigurdsson, Mark Hansen, Patrick F. Sullivan, Kieran C. Murphy, Inge Joa, Complex Trait Genetics, McLaughlin, Russell L, Schijven, Dick, Van Rheenen, Wouter, Van Eijk, Kristel R, O'Brien, Margaret, Kahn, René S, Ophoff, Roel A, Goris, An, Bradley, Daniel G, Al-Chalabi, Ammar, Van Den Berg, Leonard H, Luykx, Jurjen J, Hardiman, Orla, Veldink, Jan H, Lee, S Hong, Project MinE GWAS Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, Kučinskas, Vaidutis, Kučinskienė, Zita Aušrelė, Other departments, Neurology, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Adult Psychiatry, Schizophrenia Working Group of the Psychiatric Genomics Consortiumz, Germeys, Inez, Robberecht, Wim, and Van Damme, Philip

Subjects
0301 basic medicine, Oncology, Genetics and Molecular Biology (all), Linkage disequilibrium, Multifactorial Inheritance, General Physics and Astronomy, Genome-wide association study, Comorbidity, VARIANTS, Neurodegenerative, Biochemistry, DISEASE, 3124 Neurology and psychiatry, Linkage Disequilibrium, Cohort Studies, 0302 clinical medicine, Genetics research, Odds Ratio, 2.1 Biological and endogenous factors, Amyotrophic lateral sclerosis, Aetiology, ARCHITECTURE, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Multidisciplinary, Chemistry (all), Motor neuron disease, Schizophrenia, BIPOLAR DISORDER, Single Nucleotide, Serious Mental Illness, 3. Good health, Mental Health, RC0346, motor neuron disease, Project MinE GWAS Consortium, medicine.medical_specialty, SUSCEPTIBILITY LOCI, Science, European Continental Ancestry Group, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Article, White People, 03 medical and health sciences, Physics and Astronomy (all), Rare Diseases, SDG 3 - Good Health and Well-being, Clinical Research, Internal medicine, MD Multidisciplinary, mental disorders, medicine, Genetics, Journal Article, Humans, Genetic Predisposition to Disease, Family, Bipolar disorder, GENOME-WIDE ASSOCIATION, Polymorphism, Biology, METAANALYSIS, business.industry, Amyotrophic Lateral Sclerosis, Human Genome, Case-control study, 3112 Neurosciences, Neurosciences, General Chemistry, Odds ratio, medicine.disease, R1, Brain Disorders, 030104 developmental biology, genetics research, Case-Control Studies, RC0321, Linear Models, PLEIOTROPY, Human medicine, 3111 Biomedicine, Biochemistry, Genetics and Molecular Biology (all), ALS, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05–21.6; P=1 × 10−4) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10−7). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08–1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies., Relatives of patients with amyotrophic lateral sclerosis have an unexpectedly high incidence of schizophrenia. Here, the authors show a genetic link between the two conditions, suggesting shared neurobiological mechanisms.

Published
2017

18. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group

Author

Ulrich Schall, Dominick T. Newell, Colm McDonald, Valentina Ciullo, Suresh Sundram, Neda Jahanshad, Martha E. Shenton, Daniel H. Mathalon, Jiri Horacek, Theodore D. Satterthwaite, Nhat Trung Doan, Stanley V. Catts, H. S. Temmingh, H. Yamamori, L. E. Hong, H. Guo, René S. Kahn, Dan J. Stein, Kelvin O. Lim, Jason M. Bruggemann, L. Flyckt, Randy L. Gollub, Marc L. Seal, Antonio Pereira, X. Chen, Sarah McEwen, Steven G. Potkin, Stephen M. Lawrie, Derrek P. Hibar, Masaki Fukunaga, Adrian Preda, Benedicto Crespo-Facorro, Jun Soo Kwon, P. Wan, R. W. McCarley, Patricia T. Michie, Nailin Yao, Frans Henskens, Juan R. Bustillo, Tonya White, Marek Kubicki, Tomas Melicher, Judith M. Ford, F. M. Fan, Erin W. Dickie, Rodney J. Scott, P. De Rossi, Thomas J. Whitford, Amanda E. Lyall, J. Chen, Wiepke Cahn, A. S. Corvin, David R. Roalf, Sylvain Bouix, Craig L. Hyde, Filip Spaniel, Vincent A. Magnotta, Lena K. L. Oestreich, S. Tang, Zora Kikinis, Carlos López-Jaramillo, Siren Tønnesen, Christopher D. Whelan, Z. Xie, Paul Klauser, Gaia Romana Pellicano, D. Rotenberg, Vaughan J. Carr, Thomas W. Weickert, Stefan Ehrlich, Larry J. Seidman, Clara Alloza, Claudia D. Vargas, Fleur M. Howells, Dara M. Cannon, Emma Sprooten, René C.W. Mandl, R. Roiz, Erik G. Jönsson, Bryon A. Mueller, D. Wei, Chiara Chiapponi, Kl K. Cho, J. Q. Voyvodic, J. Pineda Zapata, S. Tan, Jatin G. Vaidya, Jim Lagopoulos, K. Liu, T.G.M. van Erp, C. Knöchel, Jingjing Zhao, Rachel M. Brouwer, Andrew Zalesky, Philip R. Jansen, Ofer Pasternak, N.E.M. van Haren, V.D. Calhoun, Sinead Kelly, L. A. Jung, Ole A. Andreassen, R.E. Gur, Sara A. Paciga, Patricio O'Donnell, Dennis Velakoulis, Annerine Roos, Dmitry Isaev, F. Piras, Helena Fatouros-Bergman, Joshua Faskowitz, Ryota Hashimoto, V. Oertel-Knöchel, Diana Tordesillas-Gutiérrez, Simon McCarthy-Jones, Godfrey D. Pearlson, Covadonga M. Díaz-Caneja, Lars T. Westlye, Andrew M. McIntosh, Peter Savadjiev, Chad A. Bousman, Nerisa Banaj, P. E. Rasser, Heather C. Whalley, Hilleke E. Hulshoff Pol, David C. Glahn, Vanessa Cropley, Aristotle N. Voineskos, G. Zhang, Y. Tan, Jessica A. Turner, Celso Arango, M. Stäblein, Paul M. Thompson, Daniela Vecchio, Ian B. Hickie, Zhen Wang, Joanne Wojcik, C. Shannon Weickert, Sean N. Hatton, Raquelle I. Mesholam-Gately, Rhoshel K. Lenroot, Gianfranco Spalletta, J. X. Chen, Jean-Paul Fouche, Ingrid Agartz, Assen Jablensky, H. Xiang, Bryan J. Mowry, Michael Gill, Gary Donohoe, E. D. Goudzwaard, Ruben C. Gur, Christos Pantelis, Joost Janssen, Tiril P. Gurholt, F. Yang, Peter Kochunov, Carolyn D. Langen, Anesthesiology, Biomedical Engineering and Physics, Human Genetics, Graduate School, CCA - Imaging and biomarkers, AII - Infectious diseases, AII - Inflammatory diseases, Endocrinology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Ophthalmology, Radiotherapy, CCA - Cancer Treatment and Quality of Life, Radiology and Nuclear Medicine, Universidad de Cantabria, Radiology & Nuclear Medicine, Erasmus MC other, and Child and Adolescent Psychiatry / Psychology

Subjects
Male, Internal capsule, corpus-callosum, Image Processing, anterior commissure, Esquizofrenia, Audiology, Corpus callosum, diffusion tensor imaging (DTI), Corpus Callosum, spatial statistics, Cohort Studies, 0302 clinical medicine, Computer-Assisted, Corpus Callosum/physiopathology, 80 and over, Image Processing, Computer-Assisted, internal capsule, Aged, 80 and over, Imagen de Difusión Tensora, Brain, Middle Aged, White Matter, 3. Good health, Diffusion Magnetic Resonance Imaging/methods, Psychiatry and Mental health, medicine.anatomical_structure, Diffusion Tensor Imaging, Schizophrenia, white matter (WM), connectivity, Original Article, Female, Psychology, fractional anisotropy, Adult, medicine.medical_specialty, brain, Aged, Brain/physiopathology, Diffusion Tensor Imaging/methods, Humans, Schizophrenia/diagnostic imaging, Schizophrenia/physiopathology, White Matter/physiopathology, White Matter/ultrastructure, Young Adult, Anterior commissure, size, White matter, 03 medical and health sciences, Cellular and Molecular Neuroscience, Corona radiata, registration, Fractional anisotropy, medicine, Journal Article, Molecular Biology, Sustancia Blanca, mri, schizophrenia, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], medicine.disease, 030227 psychiatry, Diffusion Magnetic Resonance Imaging, Neuroscience, 030217 neurology & neurosurgery, Diffusion MRI
Abstract

Contains fulltext : 193179.pdf (Publisher’s version ) (Open Access) The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.

Published
2017
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19. The treatment of schizophrenia: Can we raise the standard of care?

Author

Brian I. O'Toole and Stanley V. Catts

Subjects
medicine.medical_specialty, Standard of care, business.industry, Mortality rate, Schizophrenia (object-oriented programming), Standard of Care, General Medicine, Health outcomes, 030227 psychiatry, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, medicine, Schizophrenia, Humans, Psychiatry, business, 030217 neurology & neurosurgery, Clinical psychology, Antipsychotic Agents
Abstract

Objective: There is evidence that over time health outcomes of people with schizophrenia are deteriorating rather than improving both in terms of mortality rate and levels of morbidity, even in Australia where service resourcing is substantial. Our objective was to examine the evidence of whether poor outcomes reflect decreases in treatment effectiveness and, if so, what are the barriers to improving standards of care. This review will argue that the confidence of clinicians to diagnose schizophrenia early, and provide assertive and long-term care, may be being undermined by a series of controversies in the published literature and discrepancies in clinical practice guidelines. Method: A critical review was conducted of the evidence regarding six issues of high clinical relevance to the treatment of schizophrenia formulated as questions: (1) Is schizophrenia a progressive disease? (2) Does relapse contribute to disease progression and treatment resistance? (3) When should the diagnosis of schizophrenia be made? (4) Should maintenance antipsychotic medication be discontinued in fully remitted first-episode patients? (5) Do antipsychotic medications cause deleterious reductions in cortical grey matter volumes? and (6) Are long-acting injectable antipsychotics more effective in reducing relapse rate compared to oral formulations? Results: There is reliable evidence for schizophrenia being a progressive disease with emergent treatment resistance in most cases, that relapse contributes to this treatment resistance, that maintenance antipsychotic medication should not be discontinued in remitted first-episode patients, that antipsychotic medication does not appear to cause deleterious grey matter volume changes, that maintenance antipsychotic medication reduces the mortality rate in schizophrenia and that long-acting injectable antipsychotics are more effective in preventing relapse than oral formulations. Conclusion: There is an urgent need to re-engineer the early management of schizophrenia and to routinely evaluate this type of innovation within practice-based research networks. A proposal for an assertive treatment algorithm is included.

Published
2016

20. Jumping to delusions in early psychosis

Author

Robyn Langdon, Philip B. Ward, Megan Still, Michael H. Connors, and Stanley V. Catts

Subjects
Male, medicine.medical_specialty, Psychosis, Cognitive Neuroscience, Decision Making, Intelligence, medicine.disease_cause, Delusions, Task (project management), Thinking, Executive Function, Young Adult, Jumping, Memory, Schizophrenic Psychology, medicine, Humans, Young adult, Psychiatry, Probability learning, Early psychosis, medicine.disease, Psychiatry and Mental health, Psychotic Disorders, Schizophrenia, Female, Probability Learning, Psychology
Abstract

Patients with delusions typically seek less information when making decisions than controls ("jumping-to-conclusions", JTC) and paradoxically over-adjust to counter-evidence on probabilistic reasoning tasks. Previous studies have examined JTC bias across the delusion-prone continuum, but have not considered the co-occurrence of both biases at early stages of psychosis. This was our aim.Twenty-three early psychosis patients and 19 healthy controls completed two versions of the probabilistic reasoning task: a "draws-to-decision" version (to assess JTC) and a "graded-estimates" version (to assess over-adjustment). Both versions have been used previously with clinically delusional people with schizophrenia. IQ, memory and executive function were also examined.Patients took fewer trials to reach a decision in the draws-to-decision version and showed greater over-adjustment to counter-evidence in the graded-estimates version than controls. Across groups, those who jumped to conclusions showed greater over-adjustment. Poor executive function predicted more extreme biases in controls but not in patients. Task performances were unrelated to memory. Similar results were evident in patient and control subgroups matched on IQ, and years of formal education.A jumping-to-conclusions bias and an over-adjustment bias co-occurred in the early psychosis patients. Implications are discussed concerning the role of such biases in delusion-proneness.

Published
2013

21. Attributional biases, paranoia, and depression in early psychosis

Author

Stanley V. Catts, Philip B. Ward, Megan Still, Robyn Langdon, and Michael H. Connors

Subjects
Adult, Male, Paranoid Disorders, medicine.medical_specialty, Psychosis, Adolescent, media_common.quotation_subject, Emotions, Vulnerability, Attribution bias, Delusions, Blame, Young Adult, Bias, Surveys and Questionnaires, medicine, Humans, Paranoia, Psychiatry, Depression (differential diagnoses), media_common, Depressive Disorder, Depression, General Medicine, medicine.disease, Clinical Psychology, Psychotic Disorders, Social Perception, Schizophrenia, Case-Control Studies, Female, medicine.symptom, Attribution, Psychology
Abstract

Attributional biases to externalize blame for negative events (externalizing bias) and to target other people for blame (personalizing bias) may constitute a vulnerability to psychosis. However, most research to date has only examined attributional biases in chronic patients. We examined attributional style, paranoia, and depression in early psychosis patients to assess the primacy of attributional biases in psychosis.A quasi-experimental design was adopted to compare the attributional style of patients and controls. Correlates of attributional style were also examined.Early psychosis patients and age- and gender-matched healthy controls completed the 'Internal, Personal and Situational Attributions Questionnaire'. Paranoid tendencies, suspiciousness, and depression were also assessed in both groups, while severity of current symptoms was assessed in patients.A high proportion of patients had persecutory delusions. These patients, however, did not differ from controls in externalizing or personalizing bias. Whereas suspiciousness and persecutory delusions in patients associated with externalizing bias, no bias measures associated with paranoid tendencies in either patients or controls. Counter to the pattern seen for endogenous depression, depression in patients was associated with an increased tendency to attribute events to self and a decreased tendency to attribute events to circumstances.These preliminary findings raise doubts about the primacy of attributional biases in psychosis. The novel findings with regard to depression warrant further investigation and suggest that young people, who develop depression after the onset of psychosis, may experience a need to re-establish a sense of personal control over life events that appear unpredictable.

Published
2013

22. Theory of mind in early psychosis

Author

Michael H. Connors, Megan Still, Philip B. Ward, Robyn Langdon, and Stanley V. Catts

Subjects
Psychosis, Early psychosis, medicine.disease, Developmental psychology, Psychiatry and Mental health, Schizophrenia, First episode psychosis, Theory of mind, medicine, In patient, Pshychiatric Mental Health, Psychology, Biological Psychiatry, Social functioning
Abstract

Aim: A deficit in theory of mind - the ability to infer and reason about the mental states of others - might underpin the poor social functioning of patients with psychosis. Unfortunately, however, there is considerable variation in how such a deficit is assessed. The current study compared three classic tests of theory of mind in terms of their ability to detect impairment in patients in the early stages of psychosis.

Published
2013

23. Impaired processing of binaural temporal cues to auditory scene analysis in schizophrenia

Author

Juanita Todd, Natasha Matthews, Patricia T. Michie, Stanley V. Catts, Damien J. Mannion, and Simon Finnigan

Subjects
Adult, Male, Auditory perception, medicine.medical_specialty, Auditory scene analysis, Schizophrenia (object-oriented programming), Audiology, Functional Laterality, Precedence effect, Reaction Time, medicine, Humans, Auditory system, Biological Psychiatry, Auditory Perceptual Disorders, Information processing, Auditory Threshold, Cognition, Middle Aged, Psychiatry and Mental health, medicine.anatomical_structure, Acoustic Stimulation, Auditory Perception, Schizophrenia, Female, Cues, Psychology, Perceptual Masking, Binaural recording
Abstract

It is well established that individuals with schizophrenia demonstrate alterations in auditory perception beginning at the very earliest stages of information processing. However, it is not clear how these impairments in basic information processing translate into high-order cognitive deficits. Auditory scene analysis allows listeners to group auditory information into meaningful objects, and as such provides an important link between low-level auditory processing and higher cognitive abilities. In the present study we investigated whether low-level impairments in the processing of binaural temporal information impact upon auditory scene analysis ability. Binaural temporal processing ability was investigated in 19 individuals with schizophrenia and 19 matched controls. Individuals with schizophrenia showed impaired binaural temporal processing ability on an inter-aural time difference (ITD) discrimination task. In addition, patients demonstrated impairment in two measures of auditory scene analysis. Specifically, patients had reduced ability to use binaural temporal cues to extract signal from noise in a masking level difference paradigm, and to separate the location of a source sound in the presence of an echo in the precedence effect paradigm. These findings demonstrate that individuals with schizophrenia have impairments in the accuracy with which simple binaural temporal information is encoded in the auditory system, and furthermore, this impairment has functional consequences in terms of the use of these cues to extract information in complex auditory environments.

Published
2013

24. A contribution of novel CNVs to schizophrenia from a genome-wide study of 41,321 subjects

Author

Aiden Corvin, Kenneth S. Kendler, Jouko Lönnqvist, Patricia T. Michie, Stephanie H. Witt, Annelie Nordin, Robin M. Murray, Benjamin M. Neale, Dermot Walsh, Peter Holmans, Richard A. Belliveau, Jacques Mallet, Matthew C. Keller, Hugh Gurling, Joseph I. Friedman, Giulio Genovese, Andrew Pocklington, Lieuwe de Haan, Marcelo Bertalan, Noa Carrera, Brian Kelly, Lude Franke, Carlos N. Pato, Inez Myin-Germeys, Brandon Wormley, Nicholas John Craddock, Sven Cichon, Manuel Mattheisen, Annette M. Hartmann, Ole A. Andreassen, Masashi Ikeda, Madhusudan Gujral, Edward M. Scolnick, Jeffrey A. Lieberman, Elodie Drapeau, Deborah A. Nertney, Richard Bruggeman, Bertram Müller-Myhsok, Raquelle I. Mesholam-Gately, Ingrid Melle, Jacob Gratten, Ingrid Agartz, Frans Henskens, Stephanie Godard, Andres Metspalu, Mark Weiser, Johan G. Eriksson, Christian R. Marshall, Preben Bo Mortensen, Tõnu Esko, Sarah E. Bergen, Ina Giegling, Carmel M. Loughland, Stephen W. Scherer, Panos Roussos, Colm McDonald, Douglas F. Levinson, David Cohen, Martilias S. Farrell, James J. Crowley, Sibylle G. Schwab, Stephanie Williams, Henrik B. Rasmussen, Wei Cheng, Ann Olincy, Anders D. Børglum, Andreas J. Forstner, Wenting Wu, Benedicto Crespo-Facorro, David J. Kavanagh, Aniket Shetty, Thomas Werge, Daniel P. Howrigan, Gary Donohoe, Stephan Ripke, Jo Knight, Michael Conlon O'Donovan, Erik Söderman, Luba Kalaydjieva, Silviu Alin Bacanu, Dragan M. Svrakic, Brion S. Maher, Alexander Richards, Digby Quested, Eadbhard O' Callaghan, René S. Kahn, Lili Milani, Karin V. Fuentes Fajarado, Mark Hansen, Douglas S. Greer, Sandra Meier, S. Hong Lee, Markus M. Nöthen, Brendan Bulik-Sullivan, Guiqing Cai, Lynn E. DeLisi, Thomas Hansen, Bernard Lerer, Jubao Duan, James T.R. Walters, Ulrich Schall, Ole Mors, Kai-How Farh, Randy L. Buckner, Andrew M. McIntosh, Kung-Yee Liang, Olli Pietiläinen, Colm O. Dushlaine, Paola Giusti-Rodríguez, Srdjan Djurovic, Jaana Suvisaari, Carin J. Meijer, Christos Pantelis, Peter Eichhammer, Nancy G. Buccola, Kristin K. Nicodemus, Phil Lee, Zhouzhi Wang, Dominique Campion, Rita M. Cantor, Ariel Darvasi, Christina M. Hultman, Dan Rujescu, Joshua R. Atkins, Naomi R. Wray, Michael Davidson, Michele T. Pato, Brien P. Riley, Tim B. Bigdeli, Patrik K. E. Magnusson, Aaron R. Wolen, Srinivas Thirumalai, Vahram Haroutunian, Joshua L. Roffman, Tiina Paunio, K Kähler Anna, Thomas G. Schulze, Assen Jablensky, Andrew McQuillin, Kimberley D. Chambert, John Powell, Douglas Blackwood, Ditte Demontis, Daniele Merico, Stefan Herms, Tune H. Pers, Bryan J. Mowry, Eric Strengman, Larry J. Seidman, Pablo V. Gejman, Laura Nisenbaum, Bettina Konte, Jennifer L. Moran, Donald W. Black, Michael Gill, Line Olsen, Aarno Palotie, Robert Freedman, Dalila Pinto, Abraham Reichenberg, Qingqin S. Li, Ann E. Pulver, Mark Reimers, Jurgen Del Favero, Murray J. Cairns, Patrick F. Sullivan, Deborah L. Levy, John L. Waddington, Menachem Fromer, Marcella Rietschel, Jonathan Sebat, Rolf Adolfsson, George Kirov, Veikko Salomaa, David Curtis, Rodney J. Scott, Jin P. Szatkiewicz, Jacqueline I. Goldstein, Tracey L. Petryshen, Nelson B. Freimer, Mads V. Hollegaard, Franziska Degenhardt, David M. Hougaard, Dimitris Dikeos, Pamela Sklar, Diana O. Perkins, Shaun Purcell, Yunjung Kim, Laurent Essioux, Dheeraj Malhotra, Wolfgang Maier, Eli A. Stahl, Per Hoffmann, David A. Collier, Farooq Amin, Juha Karjalainen, William M. Brandler, Clement C. Zai, A. Hofman, Nigel Williams, Hailiang Huang, Joseph D. Buxbaum, Danielle Posthuma, Kieran C. Murphy, Jonathan Pimm, Bradley T. Webb, Joel N. Hirschhorn, Elvira Bramon, Timothy G. Dinan, Jana Strohmaier, Wiepke Cahn, Erik G. Jönsson, F. Anthony O’ Neill, Dieter B. Wildenauer, Michael John Owen, Igor Nenadic, Vaughan J. Carr, Esben Agerbo, Younes Mokrab, Morten Mattingsdal, Elliot S. Gershon, Danny Antaki, Jim van Os, Bhooma Thiruvahindrapuram, Alan R. Sanders, Sang-Yun Oh, Alkes L. Price, Vihra Milanova, Juha Veijola, Chris C. A. Spencer, Nakao Iwata, Jeremy M. Silverman, Mark J. Daly, Elena Parkhomenko, Kenneth L. Davis, Jing Qin Wu, Robert W. McCarley, Steven A. McCarroll, Derek W. Morris, Douglas M. Ruderfer, Josef Frank, C. Robert Cloninger, George N. Papadimitriou, Paul Cormican, Lyudmila Georgieva, Enrico Domenici, Claudine Laurent, James L. Kennedy, Frank Dudbridge, Peter M. Visscher, Valentina Escott-Price, Inge Joa, Marian L. Hamshere, Jianxin Shi, Margot Albus, Jordan W. Smoller, Adam Savitz, T. Scott Stroup, Elizabeth Bevilacqua, James A. Knowles, William Byerley, Madeline Alexander, Stanley V. Catts, David St Clair, Sophie E. Legge, Roel A. Ophoff, Gerald Nestadt, Paul A. Tooney, and Ayman H. Fanous

Subjects
Genetics, 0303 health sciences, Genomics, Biology, medicine.disease, Genome, Phenotype, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Schizophrenia, Cohort, Etiology, medicine, Copy-number variation, Gene, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

Genomic copy number variants (CNVs) have been strongly implicated in the etiology of schizophrenia (SCZ). However, apart from a small number of risk variants, elucidation of the CNV contribution to risk has been difficult due to the rarity of risk alleles, all occurring in less than 1% of cases. We sought to address this obstacle through a collaborative effort in which we applied a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. We observed a global enrichment of CNV burden in cases (OR=1.11, P=5.7e −15 ), which persisted after excluding loci implicated in previous studies (OR=1.07, P=1.7e −6 ). CNV burden is also enriched for genes associated with synaptic function (OR = 1.68, P = 2.8e −11 ) and neurobehavioral phenotypes in mouse (OR = 1.18, P=7.3e −5 ). We identified genome-wide significant support for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. We find support at a suggestive level for nine additional candidate susceptibility and protective loci, which consist predominantly of CNVs mediated by non-allelic homologous recombination (NAHR).

Published
2016

25. Molecular evidence of N-methyl-D-aspartate receptor hypofunction in schizophrenia

Author

Samantha J. Fung, Katherine M. Allen, Thomas W. Weickert, Stanley V. Catts, Kelly A. Newell, Vibeke S. Catts, Xu-Feng Huang, Peter R. Schofield, Cynthia Shannon Weickert, Loretta Moore, and D Pellen

Subjects
Male, cognition, 0302 clinical medicine, Prefrontal cortex, prefrontal cortex, 0303 health sciences, musculoskeletal, neural, and ocular physiology, Wechsler Scales, Middle Aged, 3. Good health, Psychiatry and Mental health, medicine.anatomical_structure, Schizophrenia, NMDA receptor, Female, Schizophrenic Psychology, Original Article, Psychology, psychological phenomena and processes, Adult, medicine.medical_specialty, Genotype, Protein subunit, SNP, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Receptors, N-Methyl-D-Aspartate, behavioral disciplines and activities, 03 medical and health sciences, Cellular and Molecular Neuroscience, Internal medicine, expression, mental disorders, medicine, Humans, Genetic Predisposition to Disease, Molecular Biology, Alleles, 030304 developmental biology, medicine.disease, schizophrenia, Minor allele frequency, Dorsolateral prefrontal cortex, Protein Subunits, Endocrinology, nervous system, Case-Control Studies, Synaptic plasticity, Neuroscience, 030217 neurology & neurosurgery
Abstract

Blockade of N-methyl-D-aspartate receptors (NMDARs) produces behavior in healthy people that is similar to the psychotic symptoms and cognitive deficits of schizophrenia and can exacerbate symptoms in people with schizophrenia. However, an endogenous brain disruption of NMDARs has not been clearly established in schizophrenia. We measured mRNA transcripts for five NMDAR subunit mRNAs and protein for the NR1 subunit in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia and control (n=74) brains. Five NMDAR single-nucleotide polymorphisms (SNPs) previously associated with schizophrenia were tested for association with NMDAR mRNAs in postmortem brain and for association with cognitive ability in an antemortem cohort of 101 healthy controls and 48 people with schizophrenia. The NR1 subunit (mRNA and protein) and NR2C mRNA were decreased in postmortem brain from people with schizophrenia (P=0.004, P=0.01 and P=0.01, respectively). In the antemortem cohort, the minor allele of NR2B rs1805502 (T5988C) was associated with significantly lower reasoning ability in schizophrenia. In the postmortem brain, the NR2B rs1805502 (T5988C) C allele was associated with reduced expression of NR1 mRNA and protein in schizophrenia. Reduction in NR1 and NR2C in the DLPFC of people with schizophrenia may lead to altered NMDAR stoichiometry and provides compelling evidence for an endogenous NMDAR deficit in schizophrenia. Genetic variation in the NR2B gene predicts reduced levels of the obligatory NR1 subunit, suggesting a novel mechanism by which the NR2B SNP may negatively influence other NMDAR subunit expression and reasoning ability in schizophrenia.

Published
2012

26. Evidence of aberrant DNA damage response signalling but normal rates of DNA repair in dividing lymphoblasts from patients with schizophrenia

Author

Assen Jablensky, David Chandler, Cynthia Shannon Weickert, Martin F. Lavin, Vibeke S. Catts, and Stanley V. Catts

Subjects
Adult, Male, DNA Repair, DNA damage, DNA repair, Immunofluorescence, Flow cytometry, Histones, Andrology, Cell Line, Tumor, medicine, Humans, DNA Breaks, Double-Stranded, Lymphocytes, Biological Psychiatry, biology, medicine.diagnostic_test, Lymphoblast, Cell Cycle, Cell cycle, Flow Cytometry, medicine.disease, Chromatin, Psychiatry and Mental health, Histone, Biochemistry, Schizophrenia, biology.protein, Biomarkers, DNA Damage
Abstract

Cancer incidence in schizophrenia is not increased commensurate with higher rates of risk exposures. Here we report an investigation of the DNA damage response, an anti-tumorigenic defence, in immortalised lymphoblasts from patients with schizophrenia.Unirradiated and irradiated (5Gy) lymphoblasts from schizophrenia patients (n = 28) and healthy controls (n = 28) were immunostained for the phosphorylated histone variant H2AX (γH2AX), an index of DNA double-strand breaks. Flow cytometry was used to assess cell cycle distribution and γH2AX immunofluorescence. Rate of DNA repair was quantified by determining the temporal change in γH2AX values following irradiation.In unirradiated lymphoblasts, γH2AX levels were significantly increased in the schizophrenia group compared with controls (effect size = 0.86). This increase was most evident in patients with cognitive deficits. In irradiated lymphoblasts, peak radiation-induced γH2AX levels were significantly reduced in patients. No differences between patients and controls were found in the rate of DNA repair or in cell cycle distribution.The significant differences in DNA damage response signalling observed involve modification of histone variant H2AX and thereby implicate regulatory processes determining chromatin structure in dividing lymphoblasts from patients with schizophrenia. The role that aberrant DNA damage response signalling plays in protecting patients from cancer is unclear.

Published
2011

27. ASPR Poster Presentations

Author

Brian I. O'Toole, Stanley V. Catts, Aaron D. J. Frost, and Vibeke S. Catts

Subjects
medicine.medical_specialty, education.field_of_study, business.industry, Incidence (epidemiology), Confounding, Population, Cancer, General Medicine, medicine.disease, 030227 psychiatry, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Schizophrenia, Internal medicine, Meta-analysis, Medicine, 030212 general & internal medicine, First-degree relatives, business, Psychiatry, Lung cancer, education
Abstract

Introduction: Whilst there is robust evidence of excess medical comorbidity in patients with schizophrenia, there are conflicting findings concerning cancer incidence rates in this population.Aim: To carry out a meta-analysis of published studies on the cancer incidence in patients with schizophrenia and their first degree relatives.Method: Meta-analysis was performed on standardised incidence ratios (SIR) of cancer in patients with schizophrenia and first degree relatives compared to general population samples.Results: The pooled overall cancer incidence in patients was notsignificantly increased (SIR1.05, CI 0.951.15). Lung cancer incidence was slightly increased (SIR1.31, CI 1.011.71), but it was reduced after adjusting for smoking prevalence. The incidence of several cancers unrelated to smoking was reduced in patients. The pooled overall cancer incidence in siblings (SIR0.89, CI 0.840.94) and parents (SIR0.90, CI 0.880.93) was significantly reduced.Conclusions: There is direct evidence of a discrepancy between cancer risk exposure and cancer incidence in patients with schizophrenia, and indirect evidence that this discrepancy is unlikely to result from confounding effects of medication or lower detection rates in patients.

Published
2007

28. Defective Self and/or Other Mentalising in Schizophrenia: A Cognitive Neuropsychological Approach

Author

Max Coltheart, Robyn Langdon, Stanley V. Catts, Patricia T. Michie, Philip B. Ward, and Neil McConaghy

Subjects
Recall, Mechanism (biology), Cognitive Neuroscience, Patient subgroups, Neuropsychology, Cognition, medicine.disease, Task (project management), Psychiatry and Mental health, Symptom profiles, Schizophrenia, medicine, Psychology, Cognitive psychology
Abstract

The mentalising abilities of schizophrenic patients and normal controls were tested using picture sequencing and story-telling tasks that required subjects to infer causal mental states in story characters, and a recall task that required subjects to dissociate subjective mental states from objective realities. Selective mentalising deficits were found in some patients. For other patients, general sequencing errors, "sensory" mentalising, and poor recall of symbolic representations suggested more profound problems. Task results were best accounted for by dissociable cognitive abnormalities, rather than graded dysfunction of a central mentalising mechanism. Symptom profiles of patient subgroups and correlations between task measures and clinical ratings linked these cognitive abnormalities to specific symptoms. General sequencing difficulty was associated with both poverty symptoms and reality distortion, suggesting that two mechanisms may underpin such errors: one, inability to manipulate symbolic representations, being linked to poverty; the other, failure to critically evaluate plausible cause-and-effect, being linked to reality distortion. There was some evidence that defective self-monitoring underpins thought disorder. Impaired metarepresentation was linked to the autisticlike symptoms of flat affect, social dysfunction, and alogia, rather than reality distortion. Implications of these findings are discussed with respect to theoretical and methodological issues confronting current schizophrenia research.

Published
2014

29. Elevated peripheral cytokines characterize a subgroup of people with schizophrenia displaying poor verbal fluency and reduced Broca's area volume

Author

Stu G. Fillman, Cynthia Shannon Weickert, Thomas W. Weickert, Rhoshel K. Lenroot, Stanley V. Catts, Jason M. Bruggemann, and Vibeke S. Catts

Subjects
Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Schizoaffective disorder, behavioral disciplines and activities, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Internal medicine, medicine, Image Processing, Computer-Assisted, Dementia, Verbal fluency test, Humans, Broca's area, Molecular Biology, Language, Intelligence Tests, Psychiatric Status Rating Scales, Brain Diseases, Brain Mapping, Verbal Behavior, Brain, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Broca Area, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, Cytokine, Endocrinology, Psychotic Disorders, Schizophrenia, Brain size, Cytokines, Female, Original Article, Psychopharmacology, Psychology, Neuroscience, 030217 neurology & neurosurgery
Abstract

Previous studies on schizophrenia have detected elevated cytokines in both brain and blood, suggesting neuroinflammation may contribute to the pathophysiology in some cases. We aimed to determine the extent to which elevated peripheral cytokine messenger RNA (mRNA) expression: (1) characterizes a subgroup of people with schizophrenia and (2) shows a relationship to cognition, brain volume and/or symptoms. Forty-three outpatients with schizophrenia or schizoaffective disorder and matched healthy controls were assessed for peripheral cytokine mRNAs (interleukin (IL)-1β, IL-2, IL-6, IL-8 and IL-18), intelligence quotient, memory and verbal fluency, symptom severity and cortical brain volumes integral to language (that is, Broca’s and Wernicke’s areas). IL-1β mRNA levels were 28% increased in schizophrenia compared with controls (t(82)=2.64, P

Published
2014

30. Biological insights from 108 schizophrenia-associated genetic loci

Author

Svetlana A. Limborska, Panos Roussos, Benjamin M. Neale, Naser Durmishi, Derek W. Morris, Douglas M. Ruderfer, Mythily Subramaniam, Paul Cormican, Alexander Richards, Margot Albus, Lyudmila Georgieva, Sandra Meier, Ulrich Schall, Giulio Genovese, Pak C. Sham, Kai-How Farh, Randy L. Buckner, Qingqin S. Li, Jubao Duan, Carlos N. Pato, Sena Karachanak-Yankova, Nicholas John Craddock, Ole Mors, Chris C. A. Spencer, Miaoxin Li, Jim van Os, Richard Bruggeman, Antonio Julià, Srinivas Thirumalai, Vahram Haroutunian, Michael Davidson, Rodney J. Scott, George N. Papadimitriou, Noa Carrera, Nelson B. Freimer, Michele T. Pato, Mads V. Hollegaard, Hon-Cheong So, Annette M. Hartmann, Ole A. Andreassen, Rolf Adolfsson, Milica Pejovic-Milovancevic, Sarah E. Bergen, S. Hong Lee, Kang Sim, Steven A. McCarroll, Sarah Tosato, Milan Macek, Béla Melegh, Qiang Wang, Ina Giegling, Wei Cheng, Mari Nelis, Assen Jablensky, Jens R. Wendland, Christian Hammer, Paola Giusti-Rodríguez, Jonathan Pimm, Petr Slominsky, Raymond C.K. Chan, Thomas Werge, Jaana Suvisaari, Shaun Purcell, Tõnu Esko, Masashi Ikeda, Bryan J. Mowry, Janis Klovins, C. Robert Cloninger, Mark Hansen, Wiepke Cahn, Olli Pietiläinen, Naomi R. Wray, John L. Waddington, Xuebin Zheng, Eric F.C. Cheung, Madeline Alexander, Jordan W. Smoller, Jacqueline I. Goldstein, Veikko Salomaa, Gary Donohoe, Enrico Domenici, Colm McDonald, Martilias S. Farrell, Stanley V. Catts, Stacy Steinberg, Stephanie Williams, Carmel M. Loughland, Jo Knight, Zita Ausrele Kucinskiene, Jin P. Szatkiewicz, Stephan Ripke, Robert W. McCarley, Yunjung Kim, David St Clair, David Curtis, Todd Lencz, Michael John Owen, Srdjan Djurovic, Nancy G. Buccola, Frans Henskens, Michael Gill, Joshua L. Roffman, Dan Rujescu, Danielle Posthuma, Tao Li, Phil Lee, Thomas Hansen, Wolfgang Maier, Judit Bene, Michael Conlon O'Donovan, Josef Frank, Nakao Iwata, Jeremy M. Silverman, Mark J. Daly, Elena Parkhomenko, Kenneth L. Davis, Sophie E. Legge, Roel A. Ophoff, Gerald Nestadt, Claudine Laurent, Pamela Sklar, Diana O. Perkins, Stefan Herms, Fritz Zimprich, Juha Karjalainen, Vera Golimbet, Anna K. Kähler, Clement C. Zai, Nigel Williams, Joseph D. Buxbaum, Ann Olincy, Anders D. Børglum, Andrey Khrunin, Jianjun Liu, Bettina Konte, Guiqing Cai, Henrik B. Rasmussen, René S. Kahn, Lili Milani, John Powell, Srihari Gopal, Johan G. Eriksson, David Cohen, Eric Y.H. Chen, James L. Kennedy, Thomas G. Schulze, Richard A. Belliveau, Colm O'Dushlaine, Peter M. Visscher, Valentina Escott-Price, Hana Kuzelova-Ptackova, Stephanie Godard, Martin Begemann, Morten Mattingsdal, Sara Marsal, Alan R. Sanders, Kari Stefansson, Brendan Bulik-Sullivan, Andres Metspalu, Per Hoffmann, Erik Söderman, James T.R. Walters, Hannelore Ehrenreich, Marion Friedl, Brion S. Maher, Teimuraz Silagadze, Annelie Nordin, Raquelle I. Mesholam-Gately, Ingrid Melle, Peter Eichhammer, Dragan M. Svrakic, A. Hofman, Kenneth S. Kendler, Laura Nisenbaum, Hailiang Huang, Sang-Yun Oh, Alkes L. Price, Mark Weiser, Preben Bo Mortensen, J. Mallet, Robin M. Murray, Bradley T. Webb, Vihra Milanova, Ayman H. Fanous, Vaidutis Kučinskas, Jennifer L. Moran, Donald W. Black, Elodie Drapeau, Nadine Cohen, George Kirov, Daniel R. Weinberger, Andrew McQuillin, Patrik K. E. Magnusson, Elvira Bramon, Tune H. Pers, Jianxin Shi, Richard E. Straub, Aiden Corvin, Jimmy Lee Chee Keong, Tiina Paunio, Brien P. Riley, Douglas Blackwood, Juha Veijola, Peter Holmans, Larry J. Seidman, Ronald Y.L. Chen, Pablo V. Gejman, Digby Quested, Erik G. Jönsson, Jeffrey A. Lieberman, Emily H. M. Wong, Tracey L. Petryshen, Franziska Degenhardt, Mark Reimers, Jurgen Del Favero, Markus M. Noethen, Hugh Gurling, Joseph I. Friedman, Andrew Pocklington, Aaron R. Wolen, Abraham Reichenberg, T. Scott Stroup, Elizabeth Bevilacqua, Silviu Alin Bacanu, Aarno Palotie, Robert Freedman, Patricia T. Michie, David M. Hougaard, F. Anthony O'Neill, Kung-Yee Liang, Jouko Lönnqvist, Inez Myin-Germeys, Draga Toncheva, Liene Nikitina-Zake, David J. Kavanagh, Rita M. Cantor, Kimberly Chambert, James J. Crowley, Ann E. Pulver, Ariel Darvasi, Christina M. Hultman, Brandon Wormley, Dai Wang, Deborah A. Nertney, Menachem Fromer, Younes Mokrab, Marcella Rietschel, Christos Pantelis, Dimitris Dikeos, Jan Lubinski, Laurent Essioux, Lieuwe de Haan, Eadbhard O'Callaghan, James A. Knowles, William Byerley, Manuel Mattheisen, Edward M. Scolnick, Line Olsen, Ingrid Agartz, Jana Strohmaier, Siow Ann Chong, Eli A. Stahl, David A. Collier, Farooq Amin, Joel N. Hirschhorn, Timothy G. Dinan, Elisabeth Stögmann, Hreinn Stefansson, Inge Joa, Dieter B. Wildenauer, Marian L. Hamshere, Frank Dudbridge, Sibylle G. Schwab, Esben Agerbo, Bernard Lerer, Andrew M. McIntosh, Carin J. Meijer, Stephanie H. Witt, Dermot Walsh, Lude Franke, Sven Cichon, Kristin K. Nicodemus, Dominique Campion, Tim B. Bigdeli, Ditte Demontis, Sergi Papiol, Hualin Simon Xi, Eric Strengman, Engilbert Sigurdsson, Patrick F. Sullivan, Kieran C. Murphy, Bertram Mueller-Myhsok, Vaughan J. Carr, Igor Nenadic, Matthew C. Keller, Christian R. Schubert, Jacob Gratten, Douglas F. Levinson, Luba Kalaydjieva, Anil K. Malhotra, Psychiatrie & Neuropsychologie, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), RS: MHeNs - R2 - Mental Health, Myin-Germeys, Inez, Perceptual and Cognitive Neuroscience (PCN), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), Complex Trait Genetics, Functional Genomics, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Ripke, Stephan, Neale, Benjamin M, Corvin, Aiden, Walters, James TR, Lee, S Hong, O'Donovan, Michael C, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Psychosis Endophenotypes International Consortium, Wellcome Trust Case-Control Consortium, NCA - Brain mechanisms in health and disease, Human genetics, ANS - Amsterdam Neuroscience, Adult Psychiatry, Other departments, Medical Oncology, Epidemiology, Pharmacy, Clinical Genetics, and Child and Adolescent Psychiatry / Psychology

Subjects
Multifactorial Inheritance, Glutamatergic system, Genome-wide association study, Disease, heritability, genetic risk, Synaptic Transmission, Conferring risk, drugs, DISEASE, glutamatergic neurotransmission, Odds Ratio, 2.1 Biological and endogenous factors, GWAS, Aetiology, Psychiatric genetics, Genetics, Complement component 4, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Multidisciplinary, Genome-wide association, PSYCHIATRIC-DISORDERS, Brain, BIPOLAR DISORDER, Single Nucleotide, Serious Mental Illness, 3. Good health, Multidisciplinary Sciences, Mental Health, Enhancer Elements, Genetic, Schizophrenia, Biological plausibility, Engineering sciences. Technology, Mutations, Enhancer Elements, General Science & Technology, Glutamic Acid, schizophrenia, Genome-Wide Association Study, Biology, Polymorphism, Single Nucleotide, Genetic, medicine, Humans, Genetic Predisposition to Disease, Allele, Polymorphism, METAANALYSIS, Alleles, Genetic association, IDENTIFICATION, Prevention, Common variants, Human Genome, Neurosciences, Immunity, medicine.disease, FRAMEWORK, Brain Disorders, immune system, Genetic Loci, genome-wide association studies, Mutation
Abstract

Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia. ispartof: Nature vol:511 issue:7510 pages:421-7 ispartof: location:England status: published

Published
2014

31. Mentalising, executive planning and disengagement in schizophrenia

Author

Stanley V. Catts, Robyn Langdon, Philip B. Ward, and Max Coltheart

Subjects
Psychosis, Cognitive Neuroscience, Cognitive disorder, medicine.disease, Task (project management), Developmental psychology, body regions, Psychiatry and Mental health, stomatognathic system, Schizophrenia, Theory of mind, medicine, In patient, Disengagement theory, Paranoia, medicine.symptom, Psychology, Cognitive psychology
Abstract

Introduction: Poor mentalising has been linked to particular psychotic symptoms (e.g., paranoia) and attributed to selective disruption of a mentalising module. Mentalising, executive planning, and disengagement were tested in patients with schizophrenia and healthy controls in order to evaluate this view against nonmodular accounts that attribute poor mentalising to generalised difficulty entertaining any hypothetical state of affairs and/or difficulty inhibiting salient misleading information. Method. Mentalising and disengagement were tested in a picture-sequencing task using false-belief and capture stories - the former require inferences of mental states; the latter test ability to inhibit salient misleading cues. Executive planning was tested using the Tower of London task. Results. Whereas patients as a whole showed impairments of mentalising, executive planning and disengagement, false-belief picture sequencing ability significantly predicted the odds of being a patient, after adjusting for all ot...

Published
2001

32. Schizotypy: Phenotypic Marker as Risk Factor

Author

Nathaniel McConaghy, Philip B. Ward, Stanley V. Catts, and Allison M. Fox

Subjects
Adult, Male, medicine.medical_specialty, Psychosis, Adolescent, Personality Inventory, Psychometrics, Schizotypy, behavioral disciplines and activities, Schizotypal Personality Disorder, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Psychoticism, medicine, Humans, Genetic Testing, 030212 general & internal medicine, Risk factor, Psychiatry, Screening procedures, Reproducibility of Results, Anhedonia, General Medicine, Middle Aged, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Phenotype, Schizophrenia, Female, Schizophrenic Psychology, medicine.symptom, Psychology
Abstract

Objective To evaluate measures of schizotypy as familial risk factors for schizophrenia with the aim of making recommendations for assessing schizotypy as part of screening procedures for identifying people at risk of schizophrenia. Method Published studies using self-report and interview-based measures of schizotypy to assess relatives of patients with schizophrenia are reviewed. A parent study is reported evaluating the diagnostic accuracy of parental schizotypy as assessed by three questionnaire-based measures: the Chapman Perceptual Aberration and Physical Anhedonia Scales, and the Eysenck Psychoticism Scale. Group scores for these self-report ratings of 23 parent-pairs of patients with schizophrenia, 20 parent-pairs of patients with chronic nonpsychotic psychiatric disorder, and 19 parent-pairs of healthy comparison subjects are compared. Results Consistent with published evidence that self-report measures of psychosis-proneness and schizotypy do not consistently reflect familial risk factors that are specific for schizophrenia, scores on questionnaire measures of schizotypy did not distinguish the parents of patients with schizophrenia from the parents in the other two groups. Conclusions Interview-based assessments of schizotypy better assess familial risk factors than self-report measures of schizotypy. Questionnaire measures of schizotypy should be supplemented by interview-based assessments when screening for individuals at risk of schizophrenia.

Published
2000

33. Apoptosis and schizophrenia: is the tumour suppressor gene, p53, a candidate susceptibility gene?

Author

Vibeke S. Catts and Stanley V. Catts

Subjects
Risk, Oncology, medicine.medical_specialty, Programmed cell death, Psychosis, Candidate gene, Population, Apoptosis, Neoplasms, Internal medicine, mental disorders, medicine, Humans, Genetic Predisposition to Disease, Genetic Testing, education, Biological Psychiatry, Genetic testing, education.field_of_study, medicine.diagnostic_test, business.industry, Brain, Cancer, medicine.disease, Psychiatry and Mental health, Schizophrenia, Immunology, Tumor Suppressor Protein p53, business
Abstract

This paper reviews the six published incidence studies of the relative risk of cancer in patients with schizophrenia compared with the general population. These studies used: incidence data, register case ascertainment, and controlled for age and sex. It is concluded that schizophrenia is associated with a lower risk of developing cancer. The role of apoptosis (programmed cell death) in cancer and brain development is briefly described. The possibility is explored that increased apoptosis may account for neurodevelopmental abnormalities as well as tumour resistance associated with schizophrenia. The authors propose that p53, a tumour suppressor gene central to regulation of apoptosis, should be investigated as a candidate susceptibility gene in schizophrenia.

Published
2000

34. Changes in Auditory Selective Attention and Event-Related Potentials Following Oral Administration of D-amphetamine in Humans

Author

Stanley V. Catts, Rebecca McKetin, Philip B. Ward, Richard P. Mattick, and Jimmy D. Bell

Subjects
Adult, Male, medicine.medical_specialty, Dextroamphetamine, Administration, Oral, Blood Pressure, Stimulus (physiology), Audiology, Latent inhibition, Double-Blind Method, Heart Rate, Oral administration, Event-related potential, Haloperidol, medicine, Humans, Attention, Selective attention, Amphetamine, Evoked Potentials, Pharmacology, Dose-Response Relationship, Drug, Affect, Psychiatry and Mental health, Electrophysiology, Anesthesia, Evoked Potentials, Auditory, Schizophrenia, Central Nervous System Stimulants, Female, Psychology, medicine.drug
Abstract

The effect of d-amphetamine on selective attention in humans was investigated by measuring event-related potentials (ERPs) during a complex auditory selective attention task (CSAT). The CSAT required subjects to make a button press response to infrequent target tones presented amongst tones that varied in pitch (high vs. low), location (left vs. right ear) and duration (51 ms vs. 102 ms). Healthy subjects completed the CSAT under three conditions: placebo, 10 mg and 20 mg d-amphetamine, at least one week apart. D-amphetamine produced a significant dose response increase in hit-rate and decrease in reaction time without changing false alarm rate. D-amphetamine reduced late PN to location irrelevant stimuli and pitch irrelevant stimuli in both the attended and unattended location. The effect of d-amphetamine was interpreted as a decrease in the maintenance of the attentional trace to irrelevant stimuli. However, these changes were accompanied by some evidence of processing of stimulus features in the unattended location. These results suggest that d-amphetamine improves selective attention, and decreases the maintenance of attention to irrelevant stimuli.

Published
1999

35. Auditory event-related potential indices of fronto-temporal information processing in schizophrenia syndromes: valid outcome prediction of clozapine therapy in a three-year follow-up

Author

Stanley V. Catts, Ulrich Schall, Frini Karayanidis, and Philip B. Ward

Subjects
Pharmacology, medicine.medical_specialty, genetic structures, Auditory event, Novelty, Mismatch negativity, Audiology, medicine.disease, behavioral disciplines and activities, Developmental psychology, External validity, Psychiatry and Mental health, P3a, Event-related potential, Schizophrenia, P3b, medicine, Pharmacology (medical), Psychology, psychological phenomena and processes
Abstract

Reliability, specificity, and Validity of three event-related potential (ERP) indices of non-attended and attended auditory information processing [the mismatch negativity (MMN), the novelty-P3a and the target-P3b] were assessed in 21 healthy subjects and 25 schizophrenic patients while performing a Visual discrimination task (Ignore condition) and, subsequently, an auditory discrimination task (Attend condition). Re-test reliability, as measured in a subset of 10 healthy subjects and 9 patients respectively, ranged from r = 0.4 to r = 0.8 In both groups P3a was found to be smaller in the Ignore than in the Attend condition. Patients had significantly larger P3a amplitudes than healthy subjects while their MMN and P3b amplitudes were smaller. Two ERP factors were extracted in healthy subjects: (I) 'novelty reaction' with high loading scores for P3a and (2) 'deviant detection' with high loading scores for MMN. P3b was predominantly loading on the first factor thus confirming partly overlapping P3a and P3b generators. However, considerable variance was also shared by the second factor, particularly in patients. External validity of the ERP factors was confirmed post hoc. Particularly ERP indices of deviant detection were found to be associated with negative symptoms. In order to assess further clinical relevance, therapy response to clozapine was followed-up over 3 yr in a sub-sample of 17 patients. Poor treatment response was associated with high Novelty Factor scores and large P3a amplitudes whereas good response was associated with high Deviant Factor scores and relatively intact MMN. It is concluded that ERP abnormalities provide a severity index of brain impairment and a measure of predicting therapeutic outcome.

Published
1999

36. Risperidone versus haloperidol: II. Cost-effectiveness

Author

Nicholas A Keks, Tim Lambert, Stanley V. Catts, Alison Davies, Paul C. Langley, and Isaac Schweitzer

Subjects
medicine.medical_specialty, Cost effectiveness, Total cost, Indirect costs, Haloperidol, Humans, Medicine, Pharmacology (medical), Psychiatry, health care economics and organizations, Pharmacology, Response rate (survey), Health economics, Risperidone, business.industry, Decision Trees, Australia, Models, Economic, Emergency medicine, Economic evaluation, Costs and Cost Analysis, Schizophrenia, business, Antipsychotic Agents, medicine.drug
Abstract

Australia and Canada are currently the only Western nations with government guidelines for analyzing the cost-effectiveness of drugs. We used guidelines issued by the Australian Pharmaceutical Benefits Advisory Committee to construct a model for comparing the cost-effectiveness of risperidone and haloperidol over a 2-year period in patients with chronic schizophrenia. Use of clozapine was also included in the analysis as an alternative treatment given to patients who proved unresponsive to therapy with haloperidol or risperidone. Results are expressed in Australian dollars. Cost-effectiveness was determined by using decision-analytic modeling to compare clinical outcomes and costs. The analytic model contained a decision tree for each of the compared agents that tracked the distribution of patients between treatment outcome pathways (ie, scenarios). Distributions were based on probabilities derived from our meta-analysis results reported elsewhere and from other sources. Each scenario had an associated monetary cost that included all significant direct costs (ie, hospital costs; outpatient costs; and the cost of drugs, the services of health care professionals, and government-subsidized hostel accommodation). The cost for a given outcome was the sum of costs for all scenarios leading to that outcome. Cost-effectiveness was expressed as the total cost per favorable outcome. The definition of a favorable outcome was one in which the patient was in a response phase at the end of the 2-year period. The probability of a patient experiencing a favorable outcome at the end of 2 years was 78.9% for risperidone versus 58.9% for haloperidol. The total cost of treatment for 2 years was $15,549.00 for risperidone versus $18,332.00 for haloperidol. The expected cost per favorable outcome was $19,709.00 for risperidone and $31,104.00 for haloperidol. Risperidone was more cost-effective than haloperidol and therefore was “dominant” in pharmacoeconomic terms because it produced a higher proportion of favorable outcomes at lower cost. Sensitivity analysis showed that the difference in clinical response rate was a key determinant of cost-effectiveness.

Published
1998

37. EXPECTANCY PRIMING AND THE SCHIZOPHRENIA SPECTRUM

Author

Stanley V. Catts, Helen J. Chenery, Simon Finnigan, Paul Bretherton, Michael S. Humphreys, David A. Copland, and Jill Harris

Subjects
Expectancy theory, Endocrine and Autonomic Systems, Cognitive Neuroscience, General Neuroscience, Schizotypy, media_common.quotation_subject, Experimental and Cognitive Psychology, medicine.disease, Neuropsychology and Physiological Psychology, Developmental Neuroscience, Neurology, Schizophrenia, medicine, Semantic memory, Personality, Psychology, Neurocognitive, Priming (psychology), Biological Psychiatry, Clinical psychology, media_common, Cognitive psychology
Abstract

Deficits in expectancy-based (EB) semantic processing are hallmark features of the neurocognitive changes associated with schizophrenia.We used dimensions of schizotypy in healthy persons as an analogue for schizophrenia to investigate how high schizotypy ratings might alter electrophysiologic measures of EB priming.These findings suggest a relationship between high schizotypal personality characteristics and alterations in the processing of distantly associated words in an EB priming task.

Published
2005

38. Increased production of interleukin-2 (IL-2) but not soluble interleukin-2 receptors (sIL-2R) in unmedicated patients with schizophrenia and schizophreniform disorder

Author

Stanley V. Catts, Neil McConaghy, Maryanne O'Donnell, Andrew R. Lloyd, Philip B. Ward, Denis Wakefield, and B. Liebert

Subjects
Adult, Male, Interleukin 2, Psychosis, Lymphocyte Activation, Peripheral blood mononuclear cell, Reference Values, Brief Psychiatric Rating Scale, medicine, Humans, Schizophreniform disorder, Biological Psychiatry, Phytohaemagglutinin, Psychiatric Status Rating Scales, biology, Thought disorder, Receptors, Interleukin-2, medicine.disease, Psychiatry and Mental health, Psychotic Disorders, Schizophrenia, Immunology, biology.protein, Interleukin-2, Female, Schizophrenic Psychology, medicine.symptom, Psychology, medicine.drug
Abstract

This study investigated immune activation, as measured by production of interleukin-2 (IL-2) and soluble interleukin-2 receptors (sIL-2R) from stimulated lymphocytes, in schizophrenia and schizophreniform disorder. The study included 13 neuroleptic-free patients, 13 medicated patients and 13 age- and sex-matched control subjects. Production of IL-2 and sIL-2R by peripheral blood mononuclear cells (PBMCs) was measured after in vitro stimulation with phytohaemagglutinin (PHA). Patients' symptoms were rated on the Scales for Assessment of Positive (SAPS) and Negative Symptoms (SANS) and the Brief Psychiatric Rating Scale (BPRS). IL-2 production by stimulated lymphocytes was significantly elevated in neuroleptic-free patients compared with both medicated patients and control subjects. IL-2 production was inversely correlated with the SAPS subscales of bizarre behaviour and formal thought disorder. The pattern of increased IL-2 production is in contrast to previous findings in patients with schizophrenia. Significant associations with clinical rating scores suggest that IL-2 production may vary in different biological subgroups of schizophrenia and schizophreniform disorder.

Published
1996

39. Remoxipride versus thioridazine in the treatment of first episodes of schizophrenia in drug-naive patients: A case for specific, low potency D2 antagonists

Author

K. Vaddadi, Tim Lambert, Nicholas A Keks, A. Zorbas, Paul C. Burnett, F. Varghese, G. Johnson, T. George, H. Hustig, J. McGrath, David L. Copolov, K. Kerr, Christine Hill, Stanley V. Catts, and Graham D. Burrows

Subjects
First episode, medicine.medical_treatment, Antagonist, Thioridazine, Pharmacology, medicine.disease, Psychiatry and Mental health, Drug-naïve, Neurology, Schizophrenia, medicine, Haloperidol, Remoxipride, Pharmacology (medical), Neurology (clinical), Antipsychotic, Psychology, medicine.drug
Abstract

Remoxipride, a substituted benzamide, is a selective D-2 antagonist with an atypical neuroleptic profile. Previous studies have demonstrated its antipsychotic efficacy against haloperidol and, more recently, thioridazine. Of the 144 patients enrolled in the Australian remoxipride-thioridazine comparative trial, 28 presented for their first episode of schizophrenia and/or had no previous neuroleptic treatment. These patients form the subject of this paper.

Published
1995

40. Clinical correlates of olfactory hallucinations in schizophrenia

Author

Robyn, Langdon, Jonathan, McGuire, Richard, Stevenson, and Stanley V, Catts

Subjects
Adult, Cross-Cultural Comparison, Male, Psychiatric Status Rating Scales, Depressive Disorder, Adolescent, Hallucinations, Psychometrics, Reproducibility of Results, Comorbidity, Middle Aged, World Health Organization, Anxiety Disorders, Delusions, Self Concept, Smell, Young Adult, Cross-Sectional Studies, Phobic Disorders, Chronic Disease, Schizophrenia, Humans, Female, Schizophrenic Psychology, Mental Status Schedule
Abstract

OBJECTIVES. Olfactory hallucinations (OHs) are underrepresented in conventional clinical instruments, infrequently researched, and poorly understood. To advance understanding of OHs, we examined their past-month prevalence and co-occurring symptoms in two datasets. DESIGN. One dataset comprised categorical codes and was examined using homogeneity analysis and logistic regression; the other dataset comprised numeric ratings and was examined using principal components analyses and linear regression. METHOD. The two datasets included: (1) 962 cases with Present State Examination - 9th Edition (PSE-9), codes (recoded present/absent) from the World Health Organization 10 Country (WHO-10) Study and (2) 265 cases with ratings on Scales for Assessing Positive/Negative Symptoms of Schizophrenia (SAPS/SANS). Two PSE-9 items (external- and self-smells) were recoded into a single OH item to examine consistency with the SAPS/SANS dataset, which contained a single OH item. RESULTS. Prevalence of OHs and hallucinations in other modalities differed according to the WHO-10 international centre. Across centres, OHs were present in 13% of the WHO-10 dataset, similar to the 17% prevalence rate in the SAPS/SANS dataset. Referential/control delusions and other hallucinations (particularly, somatic/tactile/gustatory hallucinations) were significant independent correlates of OHs in both datasets. OHs also co-occurred with social anxiety and depression in the WHO-10 dataset, with self-smells being particularly associated with self-depreciation. CONCLUSIONS. Sociocultural factors may modulate the self-reporting and/or detection of OHs and hallucinations in other modalities. Referential/control delusions promote the generation and/or maintenance of OHs independent of factors shared with other hallucinations. OHs and hallucinations of taste, touch, and bodily sensation frequently co-occur. Self-smells warrant sensitive probing.

Published
2011

41. Mismatch negativity (MMN) reduction in schizophrenia-impaired prediction--error generation, estimation or salience?

Author

Stanley V. Catts, Ulrich Schall, Juanita Todd, Patricia T. Michie, and Philip B. Ward

Subjects
Cognitive science, Conceptualization, General Neuroscience, Mean squared prediction error, Mismatch negativity, State of the Environment, Weighting, Neuropsychology and Physiological Psychology, Acoustic Stimulation, Salience (neuroscience), Memory, Physiology (medical), Schizophrenia, Animals, Humans, In patient, Attention, Schizophrenic Psychology, Psychology, Change detection, Cognitive psychology, Forecasting
Abstract

The model of mismatch negativity (MMN) as a simple index of change detection has been superseded by a richer understanding of how this event-related potential (ERP) reflects the representation of the sound environment in the brain. Our conceptualization of why the MMN is altered in certain groups must also evolve along with a better understanding of the activities reflected by this component. The detection of change incorporates processes enabling an automatic registration of “sameness”, a memory for such regularities and the application of this recent acoustic context to interpreting the present and future state of the environment. It also includes “weighting” the importance of this change to an organism's behaviour. In this light, the MMN has been considered a prediction error signal that occurs when the brain detects that the present state of the world violates a context-driven expectation about the environment. In this paper we revisit the consistent observation of reduced MMN amplitude in patients with schizophrenia. We review existing data to address whether the apparent deficit might reflect problems in prediction error generation, estimation or salience. Possible interpretations of MMN studies in schizophrenia are linked to dominant theories about the neurobiology of the illness.

Published
2011

42. Allusive Thinking in Parents of Schizophrenics

Author

Philip B. Ward, Dusan Hadzi-Pavlovic, Allison M. Fox, Nathaniel McConaghy, and Stanley V. Catts

Subjects
Male, Parents, Psychosis, Psychometrics, media_common.quotation_subject, Developmental psychology, Risk Factors, Odds Ratio, medicine, Humans, Family, media_common, Psychological Tests, Cognitive disorder, Thought disorder, medicine.disease, Psychiatry and Mental health, Schizophrenia, Meta-analysis, Test score, Female, Schizophrenic Psychology, Aptitude, medicine.symptom, Psychology
Abstract

Romney (J. Nerv. Ment. Dis. 178:481-486, 1990) performed a meta-analysis of studies examining psychometrically assessed ''thought disorder'' in the relatives of schizophrenics. He concluded that thought disorder was more prevalent in the relatives of schizophrenics than control subjects. The present review focuses on only those studies that measured ''allusive thinking'' using the Lovibond-Rapaport Object Sorting Test in parents of schizophrenics. Even when the meta-analysis included this more limited number of studies, it demonstrated that the parents of schizophrenics were 2.42 times more likely to obtain high scores on the Object Sorting Test, confirming replication of the original McConaghy (J. Neurol. Neurosurg. Psychiatry 22:243-246, 1959) finding. This effect remained significant when the original study was excluded from the meta-analysis. The predictive strength of parental Object Sorting Test score as a familial risk factor for the development of schizophrenia is discussed.

Published
1993

43. P300 Indexes Thought Disorder in Schizophrenics, but Allusive Thinking in Normal Subjects

Author

Patricia T. Michie, Anne-Marie Shelley, Philip B. Ward, Allison M. Fox, Nathaniel McConaghy, and Stanley V. Catts

Subjects
Adult, Male, Psychosis, media_common.quotation_subject, Neuropsychological Tests, Developmental psychology, Association, Thinking, Event-related potential, Terminology as Topic, medicine, Humans, Attention, Association (psychology), media_common, fungi, Thought disorder, Cognitive disorder, medicine.disease, Psychiatry and Mental health, Schizophrenia, Evoked Potentials, Auditory, Female, Schizophrenic Psychology, Aptitude, medicine.symptom, Psychology, Psychopathology, Clinical psychology
Abstract

Loosening of thinking as assessed by the Object Sorting Test (OST) has been found in a percentage of normal subjects but in a higher percentage of schizophrenics, and is familially transmitted in both groups. Loosening of thinking in normal subjects is not associated with evidence of impaired function or increased psychopathology, and in recognition of this, it was termed allusive thinking rather than thought disorder. Both OST-assessed loosening and concreteness of thinking were found to be present independently in a high percentage of schizophrenics, so that both were considered to contribute to schizophrenic thought disorder. The presence of OST-assessed loosening in schizophrenics would, therefore, be predicted to correlate partially rather than totally with measures of schizophrenic thought disorder. It has been suggested that OST-assessed loosening in normal subjects is due to a genetically determined reduction in strength of an inhibitory process that limits the spread of activation of semantic associations and results in a predisposition to schizophrenia. The brain event-related potential P300, which is, in part, under genetic control, may index this inhibitory process. Therefore, it was predicted that in normal subjects, P300 would correlate with OST-assessed loosening of associations. If schizophrenic thought disorder is due to a further weakening of this inhibitory process, it can be predicted that P300 in schizophrenics correlates only weakly with OST-assessed loosening of thinking, but more strongly with schizophrenic thought disorder. In a study in which P300 was elicited using a difficult selective attention task with 15 unmedicated schizophrenics and 22 healthy subjects, all three predictions were supported.

Published
1993

44. 5:00 PM HIGH BLOOD CYTOKINE LEVELS ARE RELATED TO DECREASED VERBAL FLUENCY AND BROCA'S AREA VOLUME REDUCTION IN SCHIZOPHRENIA

Author

Jason M. Bruggemann, Maryanne O'Donnell, Cynthia Shannon-Weickert, Rhoshel K. Lenroot, Stu G. Fillman, Stanley V. Catts, and Thomas W. Weickert

Subjects
Psychiatry and Mental health, Cytokine, Schizophrenia, medicine.medical_treatment, medicine, Volume reduction, Verbal fluency test, Broca's area, Psychology, medicine.disease, Biological Psychiatry, Developmental psychology, Clinical psychology
Published
2014

45. Psychotomimetic effects of PCP, LSD, and Ecstasy: pharmacological models of schizophrenia?

Author

Stanley V. Catts and Vibeke S. Catts

Subjects
Hallucinogen, Agonist, 5-HT2A receptor, medicine.drug_class, MDMA, Psychotomimetic, medicine.disease, Schizophrenia, mental disorders, medicine, NMDA receptor, Psychology, Neuroscience, Phencyclidine, medicine.drug
Abstract

Facts box Phencyclidine (PCP), ketamine, D-lysergic acid diethylamide (LSD) and 3, 4-methylenedioxy-methamphetamine (MDMA) have been variously referred to as schizophrenomimetics, psychotogens, or psychotomimetics. There have been many reports that these drugs can induce psychotic symptoms (hallucinations, delusions, formal thought disorder, or catatonia-like abnormalities) in the absence of delirium. here is abundant evidence that PCP induces psychotic disorder beyond the acute symptoms of intoxication. There is no clear evidence that either LSD or MDMA induces psychotic disorder, let alone schizophrenia, in individuals who did not have vulnerability to schizophrenia premorbidly. PCP and ketamine are noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) glutamatergic receptor that bind at the intrachannel site of the receptor to prevent calcium ion flux into the cell. LSD is a serotonin-like hallucinogenic indoleamine that acts as an agonist at the serotonin-subtype-2A (5HT2A) receptor, and MDMA is an indirect serotonin agonist. Rodent and primate models induced by PCP and analogues have been presented as models of human schizophrenia, with construct validity, showing homologous behavior, cognitive deficits, alterations in regional brain activation, and underlying neuronal dysfunction, to PCP-induced psychotomimetic effects in healthy volunteers and patients with schizophrenia. Ketamine is considered to be a safe and valid model of PCP psychosis and applicable to preclinical human studies. More translational science is needed to relate animal findings to humans and vice versa. In this chapter, the potential role of glutamatergic and serotonergic neurotransmitter systems in the pathophysiology of schizophrenia is examined from the perspective of the psychotomimetic effects of i) phencyclidine (PCP) and ketamine, noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) glutamatergic receptor that bind at the intrachannel site of the receptor to prevent calciumion flux into the cell; ii) D-lysergic acid diethylamide (LSD), a serotonin-like hallucinogenic indoleamine that acts as an agonist at the serotonin-subtype-2A (5HT2A) receptor; and iii) 3, 4-methylenedioxy-methamphetamine (MDMA), an indirect serotonin agonist.

Published
2010

46. High response threshold on the Lovibond-Rapaport Object Sorting Test in the parents of schizophrenics

Author

Allison M. Fox, Philip B. Ward, Michael S. Armstrong, Stanley V. Catts, and Nathaniel McConaghy

Subjects
medicine.medical_specialty, Psychosis, Future studies, media_common.quotation_subject, fungi, Cognitive disorder, Significant group, medicine.disease, Test (assessment), Schizophrenia, medicine, Aptitude, Psychiatry, Psychology, General Psychology, Clinical psychology, media_common
Abstract

McConaghy (1959, Journal of Neurology, Neurosurgery and Psychiatry, 22, 243–246) reported that parents of schizophrenic patients showed associative “loosening’ measured by the Lovibond-Rapaport Object Sorting Test (OST). Most studies that attempted to replicate this finding produced data showing statistically non-significant trends in the predicted direction. The present study explored the possibility that significant group differences have been obscured because parents of schizophrenics may make fewer responses on the OST, thereby lowering their total OST scores. Total OST scores of 23 parent-pairs of schizophrenic patients were compared with those of 19 parent-pairs of healthy controls. As in most earlier studies, parents of schizophrenics showed a non-significant trend to have raised OST scores. They also responded to significantly fewer items on the OST, i.e. showed high response threshold, compared with the parents of healthy controls. The parents of schizophrenics had significantly higher OST scores than healthy controls when the number of OST items not responded to was partialled out. It is suggested that future studies using the OST determine if the parents of schizophrenics show high response threshold and control for this effect if present.

Published
1992

47. P300 and conceptual loosening in normals: An event-related potential correlate of 'thought disorder?'

Author

Philip B. Ward, Nathaniel McConaghy, and Stanley V. Catts

Subjects
Male, medicine.medical_specialty, Adolescent, media_common.quotation_subject, Audiology, Developmental psychology, Pitch Discrimination, Thinking, Free Association, Reference Values, Event-related potential, Neuropsychologia, Reaction Time, medicine, Humans, Attention, Biological Psychiatry, media_common, Cerebral Cortex, Thought disorder, Electroencephalography, Cognition, Psychophysiology, Schizophrenia, Female, Schizophrenic Psychology, Aptitude, medicine.symptom, Arousal, Psychology, Psychopathology, Vigilance (psychology)
Abstract

Reduced amplitude of the P300 component of the event-related potential (ERP) has frequently been reported in schizophrenic patients and their first-degree relatives. The present study examined the relationship between this ERP measure of attentional processing and loosening of associations in normal university students (termed “allusive thinking”). Among male subjects, scores reflecting increased conceptual loosening, measured using the Lovibond scoring method for the Goldstein-Scheerer Object Sorting Test (OST), were significantly correlated with smaller P300 amplitude recorded during an auditory target detection task. There was no association between OST score and either performance of the target detection task of self-reported psychopathology. It is suggested that reduced P300 amplitude could reflect altered attentional processing in individuals with a constitutional trait factor of thought disorder.

Published
1992

48. Mismatch negativity: An index of a preattentive processing deficit in schizophrenia

Author

Patricia T. Michie, Stanley V. Catts, Anne-Marie Shelley, Neil McConaghy, Philip B. Ward, and Sally Andrews

Subjects
Adult, Male, Psychosis, Adolescent, media_common.quotation_subject, Mismatch negativity, Electroencephalography, Brain mapping, Developmental psychology, Pitch Discrimination, Event-related potential, Schizophrenic Psychology, medicine, Humans, Attention, Biological Psychiatry, media_common, Cerebral Cortex, Brain Mapping, medicine.diagnostic_test, medicine.disease, Evoked Potentials, Auditory, Schizophrenia, Female, Psychology, Auditory Physiology, Vigilance (psychology), Cognitive psychology
Abstract

Although there is little doubt that schizophrenics have attentional problems, the precise nature of the deficit remains obscure. Following the distinction between automatic and controlled processes (Shiffrin and Schneider 1977), some theorists have proposed that schizophrenic attention deficits are confined to controlled, or active attentional processes (Caiiaway and Naghdi 1982; Nuechterlein and Dawson 1984), whereas others have postulated an automatic, or preattentive dysfunction, such as a failure of inhibition (Johnson 1985) or defective filtering (Shagass 1976). Most event-related potential (ERP) studies of schizophrenic attention deficits suggest an impairment in controlled processing indexed by reduced P3 amplitude and an attenuation of processing negativity (PN) (Michie et al 1990; Ward et al 1991). However, it is possible that dysfunctions in controlled processes may be secondary to defects in preattentive mechanisms. Mismatch negativity (MMN) is an ERP component elicited in the auditory "oddball" paradigm by low probability "deviant" stimuli embedded in a sequence of high probability

Published
1991

49. Auditory Selective Attention and Event-Related Potentials in Schizophrenia

Author

Allison M. Fox, Stanley V. Catts, Patricia T. Michie, Philip B. Ward, and Neil McConaghy

Subjects
Adult, Male, Psychosis, media_common.quotation_subject, 050109 social psychology, Pitch Discrimination, Event-related potential, Schizophrenic Psychology, Reaction Time, medicine, Humans, Attention, 0501 psychology and cognitive sciences, Sound Localization, media_common, Cerebral Cortex, Psychiatric Status Rating Scales, 05 social sciences, Thought disorder, 050301 education, Cognition, Middle Aged, medicine.disease, Psychiatry and Mental health, Psychophysiology, Evoked Potentials, Auditory, Schizophrenia, Female, medicine.symptom, Arousal, Auditory Physiology, Psychology, 0503 education, Neuroscience, Vigilance (psychology)
Abstract

Brain ERPs were recorded in ten unmedicated schizophrenic patients and age- and sex-matched healthy controls during a multidimensional listening task. Patients showed a marked reduction in a long-duration attention-related negative ERP component, termed ‘processing negativity’ (PN), which was elicited by attended stimuli. The amplitude of PN was significantly correlated with SANS and SAPS scores of schizophrenic symptoms. The P300 component was also reduced in amplitude in patients, and was significantly correlated with SANS ratings of negative thought disorder. These findings provide neurophysiological evidence of impairment in the maintenance of selective attention and the cognitive processes associated with target detection among schizophrenic patients. The reduced PN in schizophrenics implicates frontostriatal pathways in the aetiology of attentional deficits in schizophrenia.

Published
1991

50. Neuroscience Institute of Schizophrenia and Allied Disorders (NISAD): 10 years of Australia's first virtual research institute

Author

Daren Draganic, Vaughan J. Carr, and Stanley V. Catts

Subjects
Biomedical Research, Schizophrenia (object-oriented programming), History, 21st Century, 03 medical and health sciences, User-Computer Interface, 0302 clinical medicine, Multidisciplinary approach, Humans, Narrative, Applied research, 030212 general & internal medicine, Public awareness, Academic Medical Centers, Mental Disorders, Australia, Neurosciences, General Medicine, History, 20th Century, 030227 psychiatry, Psychiatry and Mental health, Scale (social sciences), Scientific domain, Schizophrenia, Schizophrenia research, Psychology, Neuroscience
Abstract

Objective: To review the first 10 years of operation of the Neuroscience Institute of Schizophrenia and Allied Disorders (NISAD), Australia's first virtual research institute. Method: Narrative description of the evolution of NISAD. Results: Since inception in 1996, NISAD has developed a wide range of activities to enhance existing efforts and develop new initiatives in schizophrenia research, initially throughout New South Wales, but increasingly on a national scale. This involved the initial development of critical research infrastructure to provide the foundation, with the subsequent focus on developing a multidisciplinary programme of schizophrenia research, across the basic to applied research spectrum. While the primary focus has been the scientific domain, NISAD has also played a leading role in increasing public awareness of schizophrenia as a disease amenable to scientific investigation. Conclusion: NISAD has succeeded in building a framework to apply the latest developments in neuroscience to the study of schizophrenia and has formed a multidisciplinary network of clinicians and neuroscientists who are actively collaborating on a range of research initiatives. The ‘virtual institute’ structure of NISAD has proven cost-efficient and consistent with innovative thinking about research resource management.

Published
2007

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