Andrea Schmitt1,2, Daniel Martins-de-Souza2,3, Schahram Akbarian4, Juliana S Cassoli3, Hannelore Ehrenreich5, Andre Fischer6,7, Alfred Fonteh8, Wagner F Gattaz2, Michael Gawlik9, Manfred Gerlach10, Edna Grünblatt9,11,12,13, Tobias Halene4, Alkomiet Hasan1, Kenij Hashimoto14, Yong-Ku Kim15, Sophie-Kathrin Kirchner1, Johannes Kornhuber16, Theo F J Kraus17, Berend Malchow1, Juliana M Nascimento3, Moritz Rossner18,19, Markus Schwarz20, Johann Steiner21, Leda Talib2, Florence Thibaut22, Peter Riederer23, Peter Falkai1. 1. a Department of Psychiatry and Psychotherapy , LMU Munich , Germany. 2. b Laboratory of Neuroscience (LIM27) , Institute of Psychiatry, University of Sao Paulo , Sao Paulo , Brazil. 3. c Laboratory of Neuroproteomics, Department of Biochemistry , Institute of Biology University of Campinas (UNICAMP), Campinas , SP , Brazil. 4. d Division of Psychiatric Epigenomics, Departments of Psychiatry and Neuroscience , Mount Sinai School of Medicine , New York , USA. 5. e Clinical Neuroscience , Max Planck Institute of Experimental Medicine, DFG Centre for Nanoscale Microscopy & Molecular Physiology of the Brain , Göttingen , Germany. 6. f Research Group for Epigenetics in Neurodegenerative Diseases , German Centre for Neurodegenerative Diseases (DZNE), Göttingen , Germany. 7. g Department of Psychiatry and Psychotherapy , University Medical Centre Göttingen , Germany. 8. h Neurosciences , Huntington Medical Research Institutes , Pasadena , CA , USA. 9. i Department of Psychiatry and Psychotherapy , University of Würzburg , Germany. 10. j Centre for Mental Health, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy , University of Würzburg , Germany. 11. k Department of Child and Adolescent Psychiatry and Psychotherapy , Psychiatric Hospital, University of Zürich , Switzerland. 12. l Neuroscience Centre Zurich , University of Zurich and the ETH Zurich , Switzerland. 13. m Zurich Centre for Integrative Human Physiology , University of Zurich , Switzerland. 14. n Division of Clinical Neuroscience , Chiba University Centre for Forensic Mental Health , Chiba , Japan. 15. o Department of Psychiatry , Korea University, College of Medicine , Republic of Korea. 16. p Department of Psychiatry and Psychotherapy , Friedrich-Alexander-University Erlangen-Nuremberg , Erlangen , Germany. 17. q Institute of Neuropathology, LMU Munich , Germany. 18. r Department of Psychiatry, Molecular and Behavioural Neurobiology , LMU Munich , Germany. 19. s Research Group Gene Expression , Max Planck Institute of Experimental Medicine , Göttingen , Germany. 20. t Institute for Laboratory Medicine, LMU Munich , Germany. 21. u Department of Psychiatry , University of Magdeburg , Magdeburg , Germany. 22. v Department of Psychiatry , University Hospital Cochin (site Tarnier), University of Paris-Descartes, INSERM U 894 Centre Psychiatry and Neurosciences , Paris , France. 23. w Center of Psychic Health; Department of Psychiatry, Psychosomatics and Psychotherapy , University Hospital of Würzburg , Germany.
Abstract
OBJECTIVES: Despite progress in identifying molecular pathophysiological processes in schizophrenia, valid biomarkers are lacking for both the disease and treatment response. METHODS: This comprehensive review summarises recent efforts to identify molecular mechanisms on the level of protein and gene expression and epigenetics, including DNA methylation, histone modifications and micro RNA expression. Furthermore, it summarises recent findings of alterations in lipid mediators and highlights inflammatory processes. The potential that this research will identify biomarkers of schizophrenia is discussed. RESULTS: Recent studies have not identified clear biomarkers for schizophrenia. Although several molecular pathways have emerged as potential candidates for future research, a complete understanding of these metabolic pathways is required to reveal better treatment modalities for this disabling condition. CONCLUSIONS: Large longitudinal cohort studies are essential that pair a thorough phenotypic and clinical evaluation for example with gene expression and proteome analysis in blood at multiple time points. This approach might identify biomarkers that allow patients to be stratified according to treatment response and ideally also allow treatment response to be predicted. Improved knowledge of molecular pathways and epigenetic mechanisms, including their potential association with environmental influences, will facilitate the discovery of biomarkers that could ultimately be effective tools in clinical practice.
OBJECTIVES: Despite progress in identifying molecular pathophysiological processes in schizophrenia, valid biomarkers are lacking for both the disease and treatment response. METHODS: This comprehensive review summarises recent efforts to identify molecular mechanisms on the level of protein and gene expression and epigenetics, including DNA methylation, histone modifications and micro RNA expression. Furthermore, it summarises recent findings of alterations in lipid mediators and highlights inflammatory processes. The potential that this research will identify biomarkers of schizophrenia is discussed. RESULTS: Recent studies have not identified clear biomarkers for schizophrenia. Although several molecular pathways have emerged as potential candidates for future research, a complete understanding of these metabolic pathways is required to reveal better treatment modalities for this disabling condition. CONCLUSIONS: Large longitudinal cohort studies are essential that pair a thorough phenotypic and clinical evaluation for example with gene expression and proteome analysis in blood at multiple time points. This approach might identify biomarkers that allow patients to be stratified according to treatment response and ideally also allow treatment response to be predicted. Improved knowledge of molecular pathways and epigenetic mechanisms, including their potential association with environmental influences, will facilitate the discovery of biomarkers that could ultimately be effective tools in clinical practice.
Authors: Sanaz Bahari-Javan; Hristo Varbanov; Rashi Halder; Eva Benito; Lalit Kaurani; Susanne Burkhardt; Heike Anderson-Schmidt; Ion Anghelescu; Monika Budde; Roman M Stilling; Joan Costa; Juan Medina; Detlef E Dietrich; Christian Figge; Here Folkerts; Katrin Gade; Urs Heilbronner; Manfred Koller; Carsten Konrad; Sara Y Nussbeck; Harald Scherk; Carsten Spitzer; Sebastian Stierl; Judith Stöckel; Andreas Thiel; Martin von Hagen; Jörg Zimmermann; Antje Zitzelsberger; Sybille Schulz; Andrea Schmitt; Ivana Delalle; Peter Falkai; Thomas G Schulze; Alexander Dityatev; Farahnaz Sananbenesi; André Fischer Journal: Proc Natl Acad Sci U S A Date: 2017-05-22 Impact factor: 11.205
Authors: Johannes Hebebrand; Triinu Peters; Dick Schijven; Moritz Hebebrand; Corinna Grasemann; Thomas W Winkler; Iris M Heid; Jochen Antel; Manuel Föcker; Lisa Tegeler; Lena Brauner; Roger A H Adan; Jurjen J Luykx; Christoph U Correll; Inke R König; Anke Hinney; Lars Libuda Journal: Mol Metab Date: 2018-04-03 Impact factor: 7.422
Authors: Rodrigo R Nieto; Andrea Carrasco; Sebastian Corral; Rolando Castillo; Pablo A Gaspar; M Leonor Bustamante; Hernan Silva Journal: Front Psychiatry Date: 2021-06-16 Impact factor: 4.157
Authors: Roberto Carlos Agís-Balboa; Paulo S Pinheiro; Nelson Rebola; Cemil Kerimoglu; Eva Benito; Michael Gertig; Sanaz Bahari-Javan; Gaurav Jain; Susanne Burkhardt; Ivana Delalle; Alexander Jatzko; Markus Dettenhofer; Patricia A Zunszain; Andrea Schmitt; Peter Falkai; Julius C Pape; Elisabeth B Binder; Christophe Mulle; Andre Fischer; Farahnaz Sananbenesi Journal: EMBO J Date: 2017-08-02 Impact factor: 11.598