Cognition and Oculomotor Control in Model Systems of Psychosis

Abstract

Much about the mechanisms behind psychotic symptoms and syndromes is yet unknown. Studying the development of psychotic disorders remains difficult, because of confounding factors such as treatment side effects, effects of hospitalization and that most patients are seen in later stages of illness. Here, model systems can be useful. When employing model systems, it is important to explore both their strengths and their limitations in order to define which conclusions can be drawn from them.<br /> The research presented in this thesis provides insight into the strengths and limitations of two frequently used model systems of psychosis – acute ketamine administration as a state-model and high levels of schizotypy as a trait-model. Executive functions and declarative memory have been reliably demonstrated to be impaired in psychosis and smooth pursuit eye movements (SPEM) are a promising biomarker of psychosis. To better understand ketamine as a model of psychosis, research must focus on the effect of ketamine on biomarkers and cognitive symptoms and possible changes in neuronal activity during their execution. The literature on cognitive impairments in individuals with high levels of schizotypy is inconsistent. To better understand high levels of schizotypy as a model of psychosis, it is important to quantitatively assess the available literature and shape a clearer view of the current state of research in this domain. To investigate the strengths and weaknesses of these models, the work I report in this dissertation combines the methods of functional resonance imaging, eye-movement recording, computerized cognitive tasks and meta-analysis.<br /> Results reported in this thesis show that while acute ketamine administration led to impairments and neuronal alterations in SPEM and emotional memory that have been reported in psychosis, it did not impair antisaccade performance as reported in psychosis and did not lead to the neuronal changes during antisaccade performance that have been reported in psychosis. The meta-analysis of schizotypy and executive functions reported in this thesis indicates that schizotypy mimics Inhibition and Updating deficits which are also consistently reported in psychosis, but they do not lead to alterations in Shifting function, which is generally reported in psychosis. In conclusion, the research presented in this thesis suggest that ketamine and schizotypy, while being incomplete models, can be viewed as parts in a puzzle that may help to further our understanding of the etiology and pathophysiology of psychosis.