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Deconstructing Schizophrenia: Advances in Preclinical Models for Biomarker Identification

  • Judith A. PrattEmail author
  • Brian Morris
  • Neil Dawson
Chapter
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 40)

Abstract

Schizophrenia is considered to develop as a consequence of genetic and environmental factors impacting on brain neural systems and circuits during vulnerable neurodevelopmental periods, thereby resulting in symptoms in early adulthood. Understanding of the impact of schizophrenia risk factors on brain biology and behaviour can help in identifying biologically relevant pathways that are attractive for informing clinical studies and biomarker development. In this chapter, we emphasize the importance of adopting a reciprocal forward and reverse translation approach that is iteratively updated when additional new information is gained, either preclinically or clinically, for offering the greatest opportunity for discovering panels of biomarkers for the diagnosis, prognosis and treatment of schizophrenia. Importantly, biomarkers for identifying those at risk may inform early intervention strategies prior to the development of schizophrenia.

Given the emerging nature of this approach in the field, this review will highlight recent research of preclinical biomarkers in schizophrenia that show the most promise for informing clinical needs with an emphasis on relevant imaging, electrophysiological, cognitive behavioural and biochemical modalities. The implementation of this reciprocal translational approach is exemplified firstly by the production and characterization of preclinical models based on the glutamate hypofunction hypothesis, genetic and environmental risk factors for schizophrenia (reverse translation), and then the recent clinical recognition of the thalamic reticular thalamus (TRN) as an important locus of brain dysfunction in schizophrenia as informed by preclinical findings (forward translation).

Keywords

Behavioural biomarkers Biochemical biomarkers Cognition Forward translation Genetic mouse models Glutamate Imaging biomarkers NMDA receptor Oscillations Reverse translation Risk factors Thalamic reticular nucleus 

Notes

Acknowledgements

JAP, BJM and ND jointly hold an MRC research grant (MR/N012704/1). JAP and BJM currently hold MRC grants MR/N012704/1 and IMPC-74593/1 and an academic research grant from Servier. Previous support which has contributed to the development of this work includes funding from Mitsubishi Pharma and a Pfizer Translational Medicine research programme.

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Strathclyde Institute of Pharmacy and Biomedical SciencesUniversity of StrathclydeGlasgowUK
  2. 2.Institute of Neuroscience and Psychology, College of Veterinary and Life SciencesUniversity of GlasgowGlasgowUK
  3. 3.Division of Biomedical and Life Sciences, Faculty of Health and MedicineLancaster UniversityLancasterUK

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