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

Abstract

Model systems of psychosis, such as schizotypy or sleep deprivation, are valuable in informing our understanding of the etiology of the disorder and aiding the development of new treatments. Schizophrenia patients, high schizotypes, and sleep-deprived subjects are known to share deficits in oculomotor biomarkers. Here, we aimed to further validate the schizotypy and sleep deprivation models and investigated, for the first time, their interactive effects on smooth pursuit eye movements (SPEM), prosaccades, antisaccades, predictive saccades, and measures of psychotomimetic states, anxiety, depression, and stress. To do so, n = 19 controls and n = 17 high positive schizotypes were examined after both a normal sleep night and 24 h of sleep deprivation. Schizotypes displayed higher SPEM global position error, catch-up saccade amplitude, and increased psychotomimetic states. Sleep deprivation impaired SPEM, prosaccade, antisaccade, and predictive saccade performance and increased levels of psychotomimetic experiences. Additionally, sleep deprivation reduced SPEM gain in schizotypes but not controls. We conclude that oculomotor impairments are observed in relation to schizotypy and following sleep deprivation, supporting their utility as biomarkers in model systems of psychosis. The combination of these models with oculomotor biomarkers may be particularly fruitful in assisting the development of new antipsychotic or pro-cognitive drugs.

Poor sleep quality predicts psychotic‐like symptoms: an experience sampling study in young adults with schizotypal traits

“…In this case, the negative consequences of impaired sleep regulation should increase as a function of time spent awake (due to higher sleep pressure). In fact, we found increased PLEs in evening assessments as compared with daytime ones, in line with the findings of a recent study reporting increased delusional thinking and paranoid symptoms in the evening compared to the morning after sleep deprivation .…”

Differential benefits of olanzapine on executive function in schizophrenia patients: Preliminary findings

“…Although our sample sizes are small, as clinical practice moves toward individualized treatment plans, it is critical that biobehavioral measures are sensitive and reliable at an individual level . Further, small sample sizes have long been used when measuring eye‐movements in schizophrenia patients (for recent work see: Meyhofer et al, ; Seymour et al, ; Thakkar et al, ). We use eye‐movement measures in the present study to examine the effect of a drug treatment and demonstrate robust preliminary findings that significant differences can be observed using the antisaccade task.…”

Combining trait and state model systems of psychosis: The effect of sleep deprivation on cognitive functions in schizotypal individuals

“…Furthermore, schizotypy and schizophrenia overlap in terms of brain structure (e.g., reduced grey matter volume in medial prefrontal and temporal areas; Ettinger et al, 2012), and brain function (e.g., reduced activation in the insula, putamen, thalamus, and other regions during prepulse inhibition; Kumari et al, 2007Kumari et al, , 2008 as well as oculomotor control (Koychev et al, 2016;Meyhöfer et al, 2017;O'Driscoll and Callahan, 2008).…”

“…An intriguing state model system of psychosis is acute sleep deprivation (Ettinger and Kumari, 2015). Acute sleep deprivation of > 24 h evokes psychotomimetic states such as perceptual distortion, anhedonia, and cognitive disorganization (Meyhöfer et al, 2017;Petrovsky et al, 2014) as well as impairments typically linked to schizophrenia, such as deficits in oculomotor performance (Meyhöfer et al, 2016(Meyhöfer et al, , 2017 and prepulse inhibition (Petrovsky et al, 2014). These findings agree with literature showing that as sleep deprivation evokes deficits in brain areas that are also affected in schizophrenia, such as decreased metabolic activity in the prefrontal cortex, the thalamus, and the basal ganglia (Shenton et al, 2001;Shepherd et al, 2012;Thomas et al, 2000Thomas et al, , 2003.…”

“…Surprisingly, most of the previous studies have tested the effect of either the schizotypy or the sleep deprivation model. A recent study by Meyhöfer et al (2017), however, supports the importance of combining these models, as effects of sleep deprivation on smooth pursuit gain, a prominent oculomotor biomarker of psychosis, were found to be more pronounced in schizotypals than controls.…”