Emanuel Boudriot, Vanessa Gabriel, David Popovic, Pauline Pingen, Vladislav Yakimov, Sergi Papiol, Lukas Roell, Genc Hasanaj, Simiao Xu, Joanna Moussiopoulou, Siegfried Priglinger, Christoph Kern, Eva C. Schulte, Alkomiet Hasan, Oliver Pogarell, Peter Falkai, Andrea Schmitt, Benedikt Schworm, Elias Wagner
- BACKGROUND
Optical coherence tomography (OCT) and electroretinography (ERG) studies have revealed structural and functional retinal alterations in individuals with schizophrenia spectrum disorders (SSD). However, it remains unclear which specific retinal layers are affected, how the retina, brain, and clinical symptomatology are connected, and how alterations of the visual system are related to genetic disease risk.
METHODS
OCT, ERG, and brain magnetic resonance imaging (MRI) were applied to comprehensively investigate the visual system in a cohort of 103 patients with SSD and 130 healthy control individuals. The sparse partial least squares (SPLS) algorithm was used to identify multivariate associations between clinical disease phenotype and biological alterations of the visual system. The association of the revealed patterns with the individual polygenetic disease risk for schizophrenia was explored in a post hoc analysis. In addition, covariate-adjusted case-control comparisonsBACKGROUND
Optical coherence tomography (OCT) and electroretinography (ERG) studies have revealed structural and functional retinal alterations in individuals with schizophrenia spectrum disorders (SSD). However, it remains unclear which specific retinal layers are affected, how the retina, brain, and clinical symptomatology are connected, and how alterations of the visual system are related to genetic disease risk.
METHODS
OCT, ERG, and brain magnetic resonance imaging (MRI) were applied to comprehensively investigate the visual system in a cohort of 103 patients with SSD and 130 healthy control individuals. The sparse partial least squares (SPLS) algorithm was used to identify multivariate associations between clinical disease phenotype and biological alterations of the visual system. The association of the revealed patterns with the individual polygenetic disease risk for schizophrenia was explored in a post hoc analysis. In addition, covariate-adjusted case-control comparisons were performed for each individual OCT and ERG parameter.
RESULTS
The SPLS analysis yielded a phenotype-eye-brain signature of SSD in which greater disease severity, longer duration of illness, and impaired cognition were associated with electrophysiological alterations and microstructural thinning of most retinal layers. Higher individual loading onto this disease-relevant signature of the visual system was significantly associated with elevated polygenic risk for schizophrenia. In case-control comparisons, patients with SSD had lower macular thickness, thinner retinal nerve fiber and inner plexiform layers, less negative a-wave amplitude, and lower b-wave amplitude.
CONCLUSIONS
This study demonstrates multimodal microstructural and electrophysiological retinal alterations in individuals with SSD that are associated with disease severity and individual polygenetic burden.…
