Psychometric, Cognitive, and Oculomotor Characteristics of Schizotypy and Schizophrenia Spectrum Disorders

Schizophrenia spectrum disorders are considered to be among the most severe mental health issues. However, the question of their etiological mechanisms is still unsolved and requires further research. One promising approach in this context is the study of schizotypy, defined as a temporally stable set of personality traits that mimic symptoms of schizophrenia in an attenuated, subclinical form. Comparing schizotypy to the full-blown clinical disorder can help identify etiological mechanisms, including both risk and protective factors. In this thesis, I provide a detailed overview of schizotypy, including its psychometric characteristics, introduce cognitive and oculomotor continuities between schizophrenia spectrum disorders and schizotypy, and summarize discontinuities suggesting the operation of protective mechanisms in schizotypy. Subsequently, I present four original studies that build upon previous findings and fill relevant gaps left by prior research: In a psychometric study, network analysis was applied to resolve previously reported inconsistencies in one of the most widely used schizotypy questionnaires. In a behavioral investigation, I examined how schizotypy was related to cognitive functions and whether this was affected by experimentally induced sleep deprivation, a manipulation that is considered to evoke transient schizophrenia-like behaviors and experiences. In two studies combining eye tracking with psychophysical approaches, functional magnetic resonance imaging, and machine learning, I examined the cognitive, perceptual, and neural mechanisms of altered smooth pursuit eye movements (an oculomotor marker of schizophrenia) in schizotypal individuals and schizophrenia spectrum patients. Together, the studies of the present thesis indicate that similarities between schizotypy and schizophrenia spectrum disorders are selective and may be found in basic, specific sub-components of complex, high level functions rather than in the complex functions themselves. This interpretation corroborates the hypothesis that protective mechanisms operate in schizotypal individuals, suggesting that such mechanisms prevent schizotypes from displaying the full phenotype of schizophrenia spectrum disorders. Additionally, embedding the original studies presented in this thesis into previously published research, it appears that different schizophrenia like characteristics might develop in a highly differentiated fashion along a continuum from low to high levels of schizotypy. Accordingly, more advanced expressions of schizotypy might be associated with a wider range of schizophrenia-like characteristics compared to less intense expressions

Neural Correlates of Smooth Pursuit Eye Movements in Schizotypy and Recent Onset Psychosis : A Multivariate Pattern Classification Approach

Schizotypy refers to a set of personality traits that bear resemblance, at subclinical level, to psychosis. Despite evidence of similarity at multiple levels of analysis, direct comparisons of schizotypy and clinical psychotic disorders are rare. Therefore, we used functional magnetic resonance imaging (fMRI) to examine the neural correlates and task-based functional connectivity (psychophysiological interactions; PPI) of smooth pursuit eye movements (SPEM) in patients with recent onset psychosis (ROP; n = 34), participants with high levels of negative (HNS; n = 46) or positive (HPS; n = 41) schizotypal traits, and low-schizotypy control participants (LS; n = 61) using machine-learning. Despite strong previous evidence that SPEM is a highly reliable marker of psychosis, patients and controls could not be significantly distinguished based on SPEM performance or blood oxygen level dependent (BOLD) signal during SPEM. Classification was, however, significant for the right frontal eye field (FEF) seed region in the PPI analyses but not for seed regions in other key areas of the SPEM network. Applying the right FEF classifier to the schizotypal samples yielded decision scores between the LS and ROP groups, suggesting similarities and dissimilarities of the HNS and HPS samples with the LS and ROP groups. The very small difference between groups is inconsistent with previous studies that showed significant differences between patients with ROP and controls in both SPEM performance and underlying neural mechanisms with large effect sizes. As the current study had sufficient power to detect such differences, other reasons are discussed

The Network Structure of Schizotypy in the General Population

Background. Schizotypy is a set of traits that, at high levels, shows similarity with schizophrenia at various levels of analysis. Modelling the structure of schizotypy with complex networks offers novel insight into the extended psychosis phenotype. It is generally agreed that schizotypy is multidimensional, however, it is still debated whether affective dysregulation and impulsivity should be incorporated into theories and measurement of schizotypy. Methods. To estimate the network structure of schizotypy, we used data from participants recruited from the community (N = 11807) who completed the short version of the Oxford-Liverpool Inventory of Feelings and Experiences, a widespread self-report instrument that assesses the positive, negative, disorganised and impulsive domains of schizotypy. We examined the stability of the network. We performed module detection, then examined differences between modules in terms of centralities and compared the strength of edges within and between modules. Results. The estimated network was highly stable. An algorithm optimised for modularity segmented the network into modules that almost perfectly corresponded to the a priori defined subscales. Items in the disorganisation module had higher closeness centrality relative to items in the other modules, implicating that elevated disorganisation can predict more pronounced schizotypy in all the other domains (and vica versa). Conclusions. Our findings imply that the inclusion of affective dysregulation and impulsivity does not dilute the structural separation of positive, negative and disorganised schizotypy. The high closeness centrality of disorganisation concurs with classical theories positing that cognitive slippage and associative loosening are primary core features of the schizophrenic phenotype

The Network Structure of Schizotypy in the General Population

Schizotypal personality traits show similarity with schizophrenia at various levels of analysis. It is generally agreed that schizotypal personality is multidimensional, however, it is still debated whether impulsive nonconformity should be incorporated into theories and measurement of schizotypy. In addition, relatively little is known about the network structure of the four-dimensional model of schizotypal personality. To estimate the network structure of schizotypy, we used data from participants recruited from the community (N = 11807) who completed the short version of the Oxford-Liverpool Inventory of Feelings and Experiences, a widespread self-report instrument that assesses the positive, negative, disorganised and impulsive domains of schizotypy. We performed community detection, then examined differences between communities in terms of centralities and compared the strength of edges within and between communities. We found communities that almost perfectly corresponded to the a priori defined subscales (93% overlap, normalized mutual information = 0.74). Items in the disorganisation community had higher closeness centrality relative to items in the other communities (Cliff’s Δs ranged from 0.55 to 0.83) and weights of edges within the disorganisation community were stronger as compared to the negative schizotypy and impulsive nonconformity communities (Cliff’s Δs = 0.33). Our findings imply that the inclusion of impulsive nonconformity items does not dilute the classical three factor structure of positive, negative and disorganised schizotypy. The high closeness centrality of disorganisation concurs with theories positing that cognitive slippage and associative loosening are core features of the schizophrenic phenotype

Effects of nicotine on response inhibition and interference control

Nicotine is a cholinergic agonist with known procognitive effects in the domains of alerting and orienting attention. However, its effects on attentional top-down functions such as response inhibition and interference control are less well characterised. Here, we investigated the effects of 7 mg transdermal nicotine on performance on a battery of response inhibition and interference control tasks. A sample of N = 44 healthy adult non-smokers performed antisaccade, stop signal, Stroop, go/no-go, flanker, shape matching and Simon tasks, as well as the attentional network test (ANT) and a continuous performance task (CPT). Nicotine was administered in a with-in-subjects, double-blind, placebo-controlled design, with order of drug administration counterbalanced. Relative to placebo, nicotine led to significantly shorter reaction times on a prosaccade task and on CPT hits but did not significantly improve inhibitory or interference control performance on any task. Instead, nicotine had a negative influence in increasing the interference effect on the Simon task. Nicotine did not alter inter-individual associations between reaction times on congruent trials and error rates on incongruent trials on any task. Finally, there were effects involving order of drug administration, suggesting practice effects but also beneficial nicotine effects when the compound was administered first. Overall, our findings support previous studies showing positive effects of nicotine on basic attentional functions but do not provide direct evidence for an improvement of top-down cognitive control through acute administration of nicotine at this dose in healthy non-smokers.</p