title: Sleep deprivation disrupts prepulse inhibition and induces psychosis-like symptoms in healthy humans.
abstract: Translational biomarkers, such as prepulse inhibition (PPI) of the acoustic startle response, are playing an increasingly important role in the development of antipsychotic drugs for schizophrenia and related conditions. However, attempts to reliably induce a PPI deficit by psychotomimetic drugs have not been successful, leaving an unmet need for a cross-species psychosis model sensitive to this widely studied surrogate treatment target. Sleep deprivation (SD) might be such a model as it has previously been shown to induce PPI deficits in rats, which could be selectively prevented with antipsychotic but not anxiolytic or antidepressant compounds. Here, in a first proof-of-concept study we tested whether SD induces a deficit in PPI and an increase in psychosis-like symptoms in healthy humans. In two counterbalanced sessions, acoustic PPI and self-reported psychosis-like symptoms (Psychotomimetic States Inventory) were measured in 24 healthy human volunteers after a normal night's sleep and after a night of total SD. SD decreased PPI (p = 0.001) without affecting the magnitude or habituation of the startle response (all p > 0.13). SD also induced perceptual distortions, cognitive disorganization, and anhedonia (all p < 0.02). Thus, extending previous rodent work, we conclude that SD, in combination with the PPI biomarker, might be a promising translational surrogate model for psychosis as this method represents a possibility to partially and reversibly mimic the pathogenesis of psychotic states.
authors.affiliation: Departments of Psychology.
authors.forename: Nadine
authors.initials: N
authors.lastname: Petrovsky
authors.affiliation: Departments of Psychology, ulrich.ettinger@uni-bonn.de.
authors.forename: Ulrich
authors.identifier: http://orcid.org/0000-0002-0160-0281
authors.initials: U
authors.lastname: Ettinger
authors.affiliation: Departments of Psychology.
authors.forename: Antje
authors.initials: A
authors.lastname: Hill
authors.affiliation: Departments of Psychology.
authors.forename: Leonie
authors.initials: L
authors.lastname: Frenzel
authors.affiliation: Departments of Psychology.
authors.forename: Inga
authors.initials: I
authors.lastname: Meyhöfer
authors.affiliation: Psychiatry and Psychotherapy, University of Bonn, 53105 Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Wagner
authors.affiliation: Departments of Psychology.
authors.forename: Jutta
authors.initials: J
authors.lastname: Backhaus
authors.affiliation: Department of Psychology, Institute of Psychiatry, King's College London, London SE5 8AF, United Kingdom, and National Institute for Health Research, Biomedical Research Centre for Mental Health South London and Maudsley NHS Foundation Trust, London SE5 8AF, United Kingdom.
authors.forename: Veena
authors.initials: V
authors.lastname: Kumari
mesh_terms: D000161:Acoustic Stimulation; D000293:Adolescent; D000328:Adult; D059445:Anhedonia; D003072:Cognition Disorders / Q000209:etiology* / Q000503:physiopathology; D005260:Female; D006185:Habituation, Psychophysiologic / Q000502:physiology; D006801:Humans; D008297:Male; D008960:Models, Psychological; D010468:Perceptual Disorders / Q000209:etiology* / Q000503:physiopathology; D011581:Psychological Tests; D011618:Psychotic Disorders / Q000503:physiopathology; D013216:Reflex, Startle / Q000502:physiology*; D055139:Sensory Gating / Q000502:physiology*; D012892:Sleep Deprivation / Q000503:physiopathology* / Q000523:psychology; D055815:Young Adult
keywords: model system; prepulse inhibition; schizophrenia; sensorimotor gating; sleep deprivation; startle