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The impact of visual dysfunctions in recent-onset psychosis and clinical high-risk state for psychosis
Authors:Johanna M. Schwarzer  Inga Meyhoefer  Linda A. Antonucci  Lana Kambeitz-Ilankovic  Marian Surmann  Olga Bienek  Georg Romer  Udo Dannlowski  Tim Hahn  Alexandra Korda  Dominic B. Dwyer  Anne Ruef  Shalaila S. Haas  Marlene Rosen  Theresa Lichtenstein  Stephan Ruhrmann  Joseph Kambeitz  Raimo K. R. Salokangas  Christos Pantelis  Frauke Schultze-Lutter  Eva Meisenzahl  Paolo Brambilla  Alessandro Bertolino  Stefan Borgwardt  Rachel Upthegrove  Nikolaos Koutsouleris  Rebekka Lencer  the PRONIA Consortium
Abstract:Subtle subjective visual dysfunctions (VisDys) are reported by about 50% of patients with schizophrenia and are suggested to predict psychosis states. Deeper insight into VisDys, particularly in early psychosis states, could foster the understanding of basic disease mechanisms mediating susceptibility to psychosis, and thereby inform preventive interventions. We systematically investigated the relationship between VisDys and core clinical measures across three early phase psychiatric conditions. Second, we used a novel multivariate pattern analysis approach to predict VisDys by resting-state functional connectivity within relevant brain systems. VisDys assessed with the Schizophrenia Proneness Instrument (SPI-A), clinical measures, and resting-state fMRI data were examined in recent-onset psychosis (ROP, n = 147), clinical high-risk states of psychosis (CHR, n = 143), recent-onset depression (ROD, n = 151), and healthy controls (HC, n = 280). Our multivariate pattern analysis approach used pairwise functional connectivity within occipital (ON) and frontoparietal (FPN) networks implicated in visual information processing to predict VisDys. VisDys were reported more often in ROP (50.34%), and CHR (55.94%) than in ROD (16.56%), and HC (4.28%). Higher severity of VisDys was associated with less functional remission in both CHR and ROP, and, in CHR specifically, lower quality of life (Qol), higher depressiveness, and more severe impairment of visuospatial constructability. ON functional connectivity predicted presence of VisDys in ROP (balanced accuracy 60.17%, p = 0.0001) and CHR (67.38%, p = 0.029), while in the combined ROP + CHR sample VisDys were predicted by FPN (61.11%, p = 0.006). These large-sample study findings suggest that VisDys are clinically highly relevant not only in ROP but especially in CHR, being closely related to aspects of functional outcome, depressiveness, and Qol. Findings from multivariate pattern analysis support a model of functional integrity within ON and FPN driving the VisDys phenomenon and being implicated in core disease mechanisms of early psychosis states.Subject terms: Predictive markers, Psychosis
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