Consensus paper of the WFSBP Task Force on Biological Markers: Criteria for biomarkers and endophenotypes of schizophrenia, part III: Molecular mechanisms

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.

Keywords:

• Schizophrenia
• biomarkers
• proteomics
• epigenetics
• lipids

Acknowledgements

The authors thank Jacquie Klesing, Board-certified Editor in the Life Sciences (ELS), for editing assistance with the manuscript.

Disclosure statement

B. Malchow, G Stöber, J. Kornhuber, M. Gawlik, T. Kraus, M. Rossner, L. Talib, W.F. Gattaz and P. Riederer declare no conflicts of interest. A. Hasan has been invited to scientific meetings by Lundbeck, Janssen-Cilag, and Pfizer, received a paid speakership from Desitin, Otsuka and Lundbeck, and was a member of a Roche advisory board. F. Thibaut has been Editor-in-Chief of Dialogues in Clinical Neuroscience since 2015, supported by a grant from Servier. M. Jarema has been honorary speaker for Janssen, Lilly, Lundbeck, Angelini, GPharma and Servier. P. Falkai has been an honorary speaker for AstraZeneca, Bristol Myers Squibb, Eli Lilly, Essex, GE Healthcare, GlaxoSmithKline, Janssen Cilag, Lundbeck, Otsuka, Pfizer, Servier and Takeda and during the past 5 years, but not presently, has been a member of the advisory boards of Janssen-Cilag, AstraZeneca, Eli Lilly and Lundbeck. S. Iceta has been invited to scientific meetings by Servier and Menarini. A. Schmitt has been an honorary speaker for TAD Pharma and Roche and a member of advisory boards for Roche. K. Hashimoto was supported by a grant from Comprehensive Research on Disability, Health and Welfare, Agency for Medical Research and Development (AMED), Japan.

Funding

This work was supported by the Max Planck Society, the Max Planck Förderstiftung, the DFG (CNMPB), EXTRABRAIN EU-FP7, The Niedersachsen-Research Network on Neuroinfectiology (N-RENNT) of the Ministry of Science and Culture of Lower Saxony and the National Institutes of Mental Health (USA). D.M.S., J.S.C. and J.M.N. are supported by the Sao Paulo Research Foundation (FAPESP, grant numbers 13/08711-3, 14/14881-1, 14/21035-0 and 14/10068-4). The Laboratory of Neuroscience (LIM-27) receives financial support from the Associação Beneficente Alzira Denise Herzog da Silva (ABADHS). The work was supported by the European Commission under the Seventh Framework Programme (Marie-Curie IN-SENS FP7-2013-PEOPLE 607616). Furthermore, this work was funded by the German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders) under the auspices of the e:Med Programme (Grant Number 01ZX1314I SP6 to PF) and ESPRIT (grant number 01EE1407E to P.F., A.S. and B.M.).