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Biomarkers in Schizophrenia: A Brief Conceptual Consideration

DISEASE MARKERS (2013)

Journal

DISEASE MARKERS

Volume 2013, Issue -, Pages 3-9

Publisher

HINDAWI LTD

DOI: 10.1155/2013/510402

Keywords

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Categories

Biotechnology & Applied Microbiology Genetics & Heredity Medicine, Research & Experimental Pathology

Funding

NIAAA NIH HHS [R24 AA012725, R28 AA012725] Funding Source: Medline
NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [R24AA012725, R28AA012725] Funding Source: NIH RePORTER

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Abstract

Biomarkers have been sought after in the field of schizophrenia research for decades. In this paper, we discuss some of the concepts around developing biomarkers in an effort to understand why the use of biomarkers for schizophrenia has not been realized. In particular, we address the following 4 questions. Why would we need a diagnostic biomarker for schizophrenia? How is a biomarker typically defined and how does that influence the discovery of biomarkers in schizophrenia? What is the best use of biomarkers in schizophrenia? Do any biomarkers for schizophrenia currently exist? Thus, while we suggest that no biomarker currently exists for schizophrenia, the heterogeneity associated with schizophrenia will most likely need to be taken into account which will result in multiple biomarkers that identify the multiple underlying pathophysiological processes involved in schizophrenia. Therefore, much additional work will be required prior to obtaining any well-established biomarkers for schizophrenia.

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Article Psychiatry

Peripheral NF-κB dysregulation in people with schizophrenia drives inflammation: putative anti-inflammatory functions of NF-κB kinases

Caitlin E. Murphy, Adam K. Walker, Maryanne O'Donnell, Cherrie Galletly, Andrew R. Lloyd, Dennis Liu, Cynthia Shannon Weickert, Thomas W. Weickert

Summary: Elevated levels of pro-inflammatory cytokines and CRP are associated with impairments in cognitive abilities and more severe psychiatric symptoms in schizophrenia. NF-kappa B pathway genes are increased in the brains of schizophrenia patients and are closely related to neuroinflammation. IL-1 beta and IFN-gamma mRNA levels were increased in patients, while IL-6, IL-8, IL-18, and TNF-alpha mRNA levels did not differ. TLR4 and RelB appear to be more related to inflammatory status, while IKK beta and NIK are unique to high inflammation patients.

TRANSLATIONAL PSYCHIATRY (2022)

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Article Neurosciences

Virtual Ontogeny of Cortical Growth Preceding Mental Illness

Yash Patel, Jean Shin, Christoph Abe, Ingrid Agartz, Clara Alloza, Dag Alnaes, Sonia Ambrogi, Linda A. Antonucci, Celso Arango, Volker Arolt, Guillaume Auzias, Rosa Ayesa-Arriola, Nerisa Banaj, Tobias Banaschewski, Cibele Bandeira, Zeynep Basgoze, Renata Basso Cupertino, Claiton H. D. Bau, Jochen Bauer, Sarah Baumeister, Fabio Bernardoni, Alessandro Bertolino, Caterina del Mar Bonnin, Daniel Brandeis, Silvia Brem, Jason Bruggemann, Robin Bulow, Juan R. Bustillo, Sara Calderoni, Rosa Calvo, Erick J. Canales-Rodriguez, Dara M. Cannon, Susanna Carmona, Vaughan J. Carr, Stanley V. Catts, Sneha Chenji, Qian Hui Chew, David Coghill, Colm G. Connolly, Annette Conzelmann, Alexander R. Craven, Benedicto Crespo-Facorro, Kathryn Cullen, Andreas Dahl, Udo Dannlowski, Christopher G. Davey, Christine Deruelle, Covadonga M. Diaz-Caneja, Katharina Dohm, Stefan Ehrlich, Jeffery Epstein, Tracy Erwin-Grabner, Lisa T. Eyler, Jennifer Fedor, Jacqueline Fitzgerald, William Foran, Judith M. Ford, Lydia Fortea, Paola Fuentes-Claramonte, Janice Fullerton, Lisa Furlong, Louise Gallagher, Bingchen Gao, Si Gao, Jose M. Goikolea, Ian Gotlib, Roberto Goya-Maldonado, Hans J. Grabe, Melissa Green, Eugenio H. Grevet, Nynke A. Groenewold, Dominik Grotegerd, Oliver Gruber, Jan Haavik, Tim Hahn, Ben J. Harrison, Walter Heindel, Frans Henskens, Dirk J. Heslenfeld, Eva Hilland, Pieter J. Hoekstra, Sarah Hohmann, Nathalie Holz, Fleur M. Howells, Jonathan C. Ipser, Neda Jahanshad, Babette Jakobi, Andreas Jansen, Joost Janssen, Rune Jonassen, Anna Kaiser, Vasiliy Kaleda, James Karantonis, Joseph A. King, Tilo Kircher, Peter Kochunov, Sheri-Michelle Koopowitz, Mikael Landen, Nils Inge Landro, Stephen Lawrie, Irina Lebedeva, Beatriz Luna, Astri J. Lundervold, Frank P. MacMaster, Luigi A. Maglanoc, Daniel H. Mathalon, Colm McDonald, Andrew McIntosh, Susanne Meinert, Patricia T. Michie, Philip Mitchell, Ana Moreno-Alcazar, Bryan Mowry, Filippo Muratori, Leila Nabulsi, Igor Nenadic, Ruth O'Gorman Tuura, Jaap Oosterlaan, Bronwyn Overs, Christos Pantelis, Mara Parellada, Jose C. Pariente, Paul Pauli, Giulio Pergola, Francesco Maria Piarulli, Felipe Picon, Fabrizio Piras, Edith Pomarol-Clotet, Clara Pretus, Yann Quide, Joaquim Radua, J. Antoni Ramos-Quiroga, Paul E. Rasser, Andreas Reif, Alessandra Retico, Gloria Roberts, Susan Rossell, Diego Luiz Rovaris, Katya Rubia, Matthew Sacchet, Josep Salavert, Raymond Salvador, Salvador Sarro, Akira Sawa, Ulrich Schall, Rodney Scott, Pierluigi Selvaggi, Tim Silk, Kang Sim, Antonin Skoch, Gianfranco Spalletta, Filip Spaniel, Dan J. Stein, Olaf Steinstrater, Aleks Stolicyn, Yoichiro Takayanagi, Leanne Tamm, Maria Tavares, Alexander Teumer, Katharina Thiel, Sophia I. Thomopoulos, David Tomecek, Alexander S. Tomyshev, Diana Tordesillas-Gutierrez, Michela Tosetti, Anne Uhlmann, Tamsyn Van Rheenen, Javier Vazquez-Bourgon, Meike W. Vernooij, Eduard Vieta, Oscar Vilarroya, Cynthia Weickert, Thomas Weickert, Lars T. Westlye, Heather Whalley, David Willinger, Alexandra Winter, Katharina Wittfeld, Tony T. Yang, Yuliya Yoncheva, Jende L. Zijlmans, Martine Hoogman, Barbara Franke, Daan van Rooij, Jan Buitelaar, Christopher R. K. Ching, Ole A. Andreassen, Elena Pozzi, Dick Veltman, Lianne Schmaal, Theo G. M. van Erp, Jessica Turner, F. Xavier Castellanos, Zdenka Pausova, Paul Thompson, Tomas Paus

Summary: The study found that group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices across 11 cortical regions. These differences were associated with interregional profiles of prenatal cell-specific gene expression, implying that prenatal cell-specific processes may lead to deviations from typical brain development and vulnerability to mental illness. Additionally, genes coexpressed with radial glia and endothelial and mural cells were enriched with genes related to known pre/perinatal risk factors for psychosis, supporting a neurodevelopmental model of mental illness vulnerability.

BIOLOGICAL PSYCHIATRY (2022)

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Article Immunology

Peripheral complement is increased in schizophrenia and inversely related to cortical thickness

Ellen Ji, Danny Boerrigter, Helen Q. Cai, David Lloyd, Jason Bruggemann, Maryanne O'Donnell, Cherrie Galletly, Andrew Lloyd, Dennis Liu, Rhoshel Lenroot, Thomas W. Weickert, Cynthia Shannon Weickert

Summary: This study found that levels of complement factors, receptors, and regulators are significantly increased in patients with schizophrenia. Higher peripheral inflammation index scores are associated with reduced cortical thickness in the temporal lobe. These findings suggest that aberrant complement levels may play an important role in the pathophysiology of schizophrenia.

BRAIN BEHAVIOR AND IMMUNITY (2022)

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Article Biochemistry & Molecular Biology

Early Life Stress Alters Expression of Glucocorticoid Stress Response Genes and Trophic Factor Transcripts in the Rodent Basal Ganglia

Cynthia Haidee Tran, Cynthia Shannon Weickert, Thomas Wesley Weickert, Duncan Sinclair

Summary: Early life stress has long-lasting impacts on brain regions involved in dopamine neurotransmission, changing the trophic environment and potentially altering responsiveness to subsequent stressful events in a sex-specific pattern.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Biochemistry & Molecular Biology

Obesity and brain structure in schizophrenia - ENIGMA study in 3021 individuals

Sean R. McWhinney, Katharina Brosch, Vince D. Calhoun, Benedicto Crespo-Facorro, Nicolas A. Crossley, Udo Dannlowski, Erin Dickie, Lorielle M. F. Dietze, Gary Donohoe, Stefan Du Plessis, Stefan Ehrlich, Robin Emsley, Petra Furstova, David C. Glahn, Alfonso Gonzalez-Valderrama, Dominik Grotegerd, Laurena Holleran, Tilo T. J. Kircher, Pavel Knytl, Marian Kolenic, Rebekka Lencer, Igor Nenadic, Nils Opel, Julia-Katharina Pfarr, Amanda L. Rodrigue, Kelly Rootes-Murdy, Alex J. Ross, Kang Sim, Antonin Skoch, Filip Spaniel, Frederike Stein, Patrik Svancer, Diana Tordesillas-Gutierrez, Juan Undurraga, Javier Vaquez-Bourgon, Aristotle Voineskos, Esther Walton, Thomas W. Weickert, Cynthia Shannon Weickert, Paul M. Thompson, Theo G. M. van Erp, Jessica A. Turner, Tomas Hajek

Summary: Schizophrenia is associated with obesity, and the brain changes in individuals with schizophrenia are more widespread and pronounced than those associated with obesity alone. Obesity may contribute to heterogeneity of brain imaging findings in schizophrenia.

MOLECULAR PSYCHIATRY (2022)

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Correction Biochemistry & Molecular Biology

Obesity and brain structure in schizophrenia - ENIGMA study in 3021 individuals (Jun, 10.1038/s41380022-01616-5, 2022)

Sean R. McWhinney, Katharina Brosch, Vince D. Calhoun, Benedicto Crespo-Facorro, Nicolas A. Crossley, Udo Dannlowski, Erin Dickie, Lorielle M. F. Dietze, Gary Donohoe, Stefan Du Plessis, Stefan Ehrlich, Robin Emsley, Petra Furstova, David C. Glahn, Alfonso Gonzalez-Valderrama, Dominik Grotegerd, Laurena Holleran, Tilo T. J. Kircher, Pavel Knytl, Marian Kolenic, Rebekka Lencer, Igor Nenadic, Nils Opel, Julia-Katharina Pfarr, Amanda L. Rodrigue, Kelly Rootes-Murdy, Alex J. Ross, Kang Sim, Antonin Skoch, Filip Spaniel, Frederike Stein, Patrik Svancer, Diana Tordesillas-Gutierrez, Juan Undurraga, Javier Vaquez-Bourgon, Aristotle Voineskos, Esther Walton, Thomas W. Weickert, Cynthia Shannon Weickert, Paul M. Thompson, Theo G. M. van Erp, Jessica A. Turner, Tomas Hajek

MOLECULAR PSYCHIATRY (2022)

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Review Psychiatry

Efficacy of Transcranial Direct Current Stimulation to Improve Insight in Patients With Schizophrenia: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Ondine Adam, Martin Blay, Andre R. Brunoni, Hsin-An Chang, July S. Gomes, Daniel C. Javitt, Do-Un Jung, Joshua T. Kantrowitz, Sanne Koops, Jean-Pierre Lindenmayer, Ulrich Palm, Robert C. Smith, Iris E. Sommer, Leandro do Costa Lane Valiengo, Thomas W. Weickert, Jerome Brunelin, Marine Mondino

Summary: Ten sessions of tDCS can improve insight into illness in patients with schizophrenia, with age and baseline G12 score as significant moderators.

SCHIZOPHRENIA BULLETIN (2022)

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Article Biochemistry & Molecular Biology

Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium

Constantinos Constantinides, Laura K. M. Han, Clara Alloza, Linda Antonella Antonucci, Celso Arango, Rosa Ayesa-Arriola, Nerisa Banaj, Alessandro Bertolino, Stefan Borgwardt, Jason Bruggemann, Juan Bustillo, Oleg Bykhovski, Vince Calhoun, Vaughan Carr, Stanley Catts, Young-Chul Chung, Benedicto Crespo-Facorro, Covadonga M. Diaz-Caneja, Gary Donohoe, Stefan Du Plessis, Jesse Edmond, Stefan Ehrlich, Robin Emsley, Lisa T. Eyler, Paola Fuentes-Claramonte, Foivos Georgiadis, Melissa Green, Amalia Guerrero-Pedraza, Minji Ha, Tim Hahn, Frans A. Henskens, Laurena Holleran, Stephanie Homan, Philipp Homan, Neda Jahanshad, Joost Janssen, Ellen Ji, Stefan Kaiser, Vasily Kaleda, Minah Kim, Woo-Sung Kim, Matthias Kirschner, Peter Kochunov, Yoo Bin Kwak, Jun Soo Kwon, Irina Lebedeva, Jingyu Liu, Patricia Mitchie, Stijn Michielse, David Mothersill, Bryan Mowry, Victor Ortiz-Garcia de la Foz, Christos Pantelis, Giulio Pergola, Fabrizio Piras, Edith Pomarol-Clotet, Adrian Preda, Yann Quide, Paul E. Rasser, Kelly Rootes-Murdy, Raymond Salvador, Marina Sangiuliano, Salvador Sarro, Ulrich Schall, Andre Schmidt, Rodney J. Scott, Pierluigi Selvaggi, Kang Sim, Antonin Skoch, Gianfranco Spalletta, Filip Spaniel, Sophia Thomopoulos, David Tomecek, Alexander S. Tomyshev, Diana Tordesillas-Gutierrez, Therese van Amelsvoort, Javier Vazquez-Bourgon, Daniela Vecchio, Aristotle Voineskos, Cynthia S. Weickert, Thomas Weickert, Paul M. Thompson, Lianne Schmaal, Theo G. M. van Erp, Jessica Turner, James H. Cole, Danai Dima, Esther Walton

Summary: Schizophrenia patients show evidence of advanced brain ageing, which is not associated with clinical characteristics.

MOLECULAR PSYCHIATRY (2023)

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Article Multidisciplinary Sciences

Large- scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

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, Rene S. Kahn, Rosa Ayesa-Arriola, Victor Ortiz-Garcia de la Foz, Diana Tordesillas-Gutierrez, Javier Vazquez-Bourgon, Benedicto Crespo-Facorro, Dag Alnaes, Andreas Dahl, Lars T. Westlye, Ingrid Agartz, Ole A. Andreassen, Erik G. Jonsson, Peter Kochunov, Jason M. Bruggemann, Stanley V. Catts, Patricia T. Michie, Bryan J. Mowry, Yann Quide, 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 Nenadic, Bernd Kramer, 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 Sarro, 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, Andre 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. Diaz-Caneja, Joost Janssen, Noemi G. Lois, Celso Arango, Alexander S. Tomyshev, Irina Lebedeva, Simon Cervenkav, Carl M. Sellgrenv, 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 Knochel, Michael Stablein, Viola Oertel, Anne Uhlmann, Fleur M. Howells, Dan J. Stein, Henk S. Temmingh, Ana M. Diaz-Zuluaga, Julian A. Pineda-Zapata, Carlos Lopez-Jaramillo, Stephanie Homan, Ellen Ji, Werner Surbeck, Philipp Homan, Simon E. Fishera, 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

Summary: Left-right asymmetry is an important feature of the healthy brain that may be altered in schizophrenia. This study used a large sample size and consistent methods to investigate structural brain asymmetries in schizophrenia, finding significant differences. These differences may reflect changes 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.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2023)

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Editorial Material Neurosciences

A path to novel, effective treatments for schizophrenia

Thomas W. Weickert, Cynthia Shannon Weickert

NEUROPSYCHOPHARMACOLOGY (2023)

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