Deconstructing Schizophrenia: advances in preclinical models for biomarker identification

Pratt, J. A., Morris, B. and Dawson, N. (2019) Deconstructing Schizophrenia: advances in preclinical models for biomarker identification. In: Pratt, J. and Hall, J. (eds.) Biomarkers in Psychiatry. Series: Current topics in behavioral neurosciences (40). Springer: Cham, Switzerland, pp. 295-323. ISBN 9783319996417 (doi:10.1007/7854_2018_48)

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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).

Item Type:Book Sections
Additional Information: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.
Keywords:Behavioural biomarkers, biochemical biomarkers, cognition, forward translation, genetic mouse models, glutamate, imaging biomarkers, NMDA receptor, oscillations, reverse translation, risk factors, thalamic reticular nucleus.
Status:Published
Glasgow Author(s) Enlighten ID:Morris, Professor Brian
Authors: Pratt, J. A., Morris, B., and Dawson, N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Current topics in behavioral neurosciences
Publisher:Springer
ISSN:1866-3370
ISSN (Online):1866-3389
ISBN:9783319996417
Published Online:03 May 2018
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
707621Characterising mice syntenic for human 16p11.2 duplications or deletions in relation to schizophrenia and autism. ID 13267Brian MorrisMedical Research Council (MRC)MR/N012704/1INP - CENTRE FOR NEUROSCIENCE
707621Characterising mice syntenic for human 16p11.2 duplications or deletions in relation to schizophrenia and autism. ID 13267Brian MorrisMedical Research Council (MRC)MR/N012704/1INP - CENTRE FOR NEUROSCIENCE