Sleep deprivation as an experimental model system for psychosis: Effects on smooth pursuit, prosaccades, and antisaccades

Abstract

Current antipsychotic medications fail to satisfactorily reduce negative and cognitive symptoms and produce many unwanted side effects, necessitating the development of new compounds. Cross-species, experimental behavioural model systems can be valuable to inform the development of such drugs. The aim of the current study was to further test the hypothesis that controlled sleep deprivation is a safe and effective model system for psychosis when combined with oculomotor biomarkers of schizophrenia. Using a randomized counterbalanced within-subjects design, we investigated the effects of 1 night of total sleep deprivation in 32 healthy participants on smooth pursuit eye movements (SPEM), prosaccades (PS), antisaccades (AS), and self-ratings of psychosis-like states. Compared with a normal sleep control night, sleep deprivation was associated with reduced SPEM velocity gain, higher saccadic frequency at 0.2 Hz, elevated PS spatial error, and an increase in AS direction errors. Sleep deprivation also increased intra-individual variability of SPEM, PS, and AS measures. In addition, sleep deprivation induced psychosis-like experiences mimicking hallucinations, cognitive disorganization, and negative symptoms, which in turn had moderate associations with AS direction errors. Taken together, sleep deprivation resulted in psychosis-like impairments in SPEM and AS performance. However, diverging somewhat from the schizophrenia literature, sleep deprivation additionally disrupted PS control. Sleep deprivation thus represents a promising but possibly unspecific experimental model that may be helpful to further improve our understanding of the underlying mechanisms in the pathophysiology of psychosis and aid the development of antipsychotic and pro-cognitive drugs.

Combining two model systems of psychosis: The effects of schizotypy and sleep deprivation on oculomotor control and psychotomimetic states

“…Sleep deprivation also led to increased psychotomimetic states and state levels of depression and anxiety. These findings largely replicate our previous study (Meyhöfer et al, ; Petrovsky et al, ) and broadly agree with previous self‐reports of hallucinations and negative symptoms after sleep deprivation (Killgore et al, ; Luby et al, ; West et al, ). Schizophrenia patients also demonstrate higher state levels of depression (Chiappelli et al, ), further supporting the validity of the sleep deprivation model.…”

“…SPEM impairments in schizophrenia are well replicated (Levy, Sereno, Gooding, & O'Driscoll, ; O'Driscoll & Callahan, ). Similar deficits have been reported in overall high schizotypes (Koychev et al, ; Meyhöfer et al, ), in high positive, negative, and disorganized subgroups (Gooding, Miller, & Kwapil, ; Holahan & O'Driscoll, ; Lenzenweger & O'Driscoll, ; O'Driscoll, Lenzenweger, & Holzman, ; Smyrnis et al, ), and following sleep deprivation (Meyhöfer, Kumari, Hill, Petrovsky, & Ettinger, ).…”

“…Antisaccade impairments following sleep deprivation include elevated errors, increased latencies, and reduced peak velocity (Meyhöfer et al, ). In contrast to schizophrenia and schizotypy, sleep deprivation also deteriorates prosaccades (Meyhöfer et al, ).…”

“…Similarly, high schizotypes demonstrate elevated antisaccade error rates (Ettinger et al, 2005;Gooding, Shea, & Matts, 2005;Holahan & O'Driscoll, 2005;Smyrnis et al, 2003) but normal prosaccade performance (Gooding et al, 2005). Antisaccade impairments following sleep deprivation include elevated errors, increased latencies, and reduced peak velocity (Meyh€ ofer et al, 2017). In contrast to schizophrenia and schizotypy, sleep deprivation also deteriorates prosaccades (Meyh€ ofer et al, 2017).…”

iLid

“…Ahlstrom et al [11] performed a fatigue-measurement study for drivers using these techniques, but due to the aforementioned limitations they were restricted to testing the drivers’ fatigue state in a controlled immediately before and after the driving event. We do not provide related studies in this area since there is not a strong comparison to be made with our work, but we refer the reader to [51] for an excellent literature review of the state-of-the-art on this topic.…”