title: Effects of sleep deprivation on inhibitory biomarkers of schizophrenia: implications for drug development.
abstract: Development of drugs for the treatment of the clinical symptoms and cognitive deficits of schizophrenia is unsatisfactory, with many initially promising compounds not showing beneficial effects in clinical studies. Experimental model systems of schizophrenia combined with well-validated biomarkers are urgently needed to provide early indicators of effectiveness. Herein, we argue that experimentally controlled sleep deprivation represents a translational model system that can be studied in combination with neurocognitive biomarkers. Specifically, we review data on the psychotomimetic effects of sleep deprivation in healthy human beings and provide evidence of the psychosis-like deficits in translational inhibitory biomarkers-prepulse inhibition and antisaccades-that occur after sleep deprivation. These data support the use of the sleep deprivation model in combination with biomarkers with excellent psychometric properties and well-characterised neural mechanisms, such as prepulse inhibition and antisaccades, to substantially advance development of drugs with antipsychotic or pro-cognitive effects.
authors.affiliation: Department of Psychology, University of Bonn, Bonn, Germany. Electronic address: ulrich.ettinger@uni-bonn.de.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Ettinger
authors.affiliation: Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; NIHR Biomedical Research Centre for Mental Health, South London and Maudsley NHS Foundation Trust, London, UK.
authors.forename: Veena
authors.initials: V
authors.lastname: Kumari
mesh_terms: D014150:Antipsychotic Agents; D015415:Biomarkers; D003072:Cognition Disorders / Q000188:drug therapy; D055808:Drug Discovery; D006801:Humans; D065808:Prepulse Inhibition / Q000502:physiology*; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D012892:Sleep Deprivation / Q000523:psychology*
chemical_list: D014150:Antipsychotic Agents; D015415:Biomarkers