The impact of visual dysfunctions in recent-onset psychosis and clinical high-risk state for psychosis
Authors: Schwarzer Johanna M. , Meyhoefer Inga , Antonucci Linda A. , Kambeitz-Ilankovic Lana , Surmann Marian , Bienek Olga , Romer Georg , Dannlowski Udo , Hahn Tim , Korda Alexandra , Dwyer Dominic B. , Ruef Anne , Haas Shalaila S. , Rosen Marlene , Lichtenstein Theresa , Ruhrmann Stephan , Kambeitz Joseph , Salokangas Raimo K. R. , Pantelis Christos , Schultze-Lutter Frauke , Meisenzahl Eva , Brambilla Paolo , Bertolino Alessandro , Borgwardt Stefan , Upthegrove Rachel , Koutsouleris Nikolaos , Lencer Rebekka ,   the PRONIA Consortium, Hasan Alkomiet , Hoff Claudius , Khanyaree Ifrah , Melo Aylin , Muckenhuber-Sternbauer Susanna , Köhler Yanis , Öztürk Ömer , Penzel Nora , Popovic David , Rangnick Adrian , von Saldern Sebastian , Sanfelici Rachele , Spangemacher Moritz , Tupac Ana , Urquijo Maria Fernanda , Weiske Johanna , Wosgien Antonia , Krämer Camilla , Blume Karsten , Julkowski Dominika , Kaden Nathalie , Milz Ruth , Nikolaides Alexandra , Vent Mauro Silke , Wassen Martina , Andreou Christina , Egloff Laura , Harrisberger Fabienne , Heitz Ulrike , Lenz Claudia , Leanza Letizia , Mackintosh Amatya , Smieskova Renata , Studerus Erich , Walter Anna , Widmayer Sonja , Day Chris , Griffiths Sian Lowri , Iqbal Mariam , Pelton Mirabel , Mallikarjun Pavan , Stainton Alexandra , Lin Ashleigh , Lalousis Paris , Denissoff Alexander , Ellilä Anu , From Tiina , Heinimaa Markus , Ilonen Tuula , Jalo Päivi , Laurikainen Heikki , Luutonen Antti , Mäkela Akseli , Paju Janina , Pesonen Henri , Säilä Reetta-Liina , Toivonen Anna , Turtonen Otto , Botterweck Sonja , Kluthausen Norman , Antoch Gerald , Caspers Julian , Wittsack Hans-Jörg , Solana Ana Beatriz , Abraham Manuela , Schirmer Timo , Altamura Carlo , Belleri Marika , Bottinelli Francesca , Ferro Adele , Re Marta , Monzani Emiliano , Sberna Maurizio , D’Agostino Armando , Del Fabro Lorenzo , Perna Giampaolo , Nobile Maria , Alciati Alessandra , Balestrieri Matteo , Bonivento Carolina , Cabras Giuseppe , Fabbro Franco , Garzitto Marco , Piccin Sara 
Published: August 2022

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.