Genetic susceptibility to schizophrenia through neuroinflammatory pathways associated with retinal thinness

Schizophrenia is associated with structural and functional changes in the central nervous system, including the most distal part of it, the retina. However, the question of whether retinal atrophy is present before individuals develop schizophrenia or is a secondary consequence of the disorder remains unanswered. Here we address this question by examining the association between polygenic risk scores for schizophrenia and retinal morphologies in individuals without a schizophrenia diagnosis. We used population data for 34,939 white British and Irish individuals from the UK Biobank. Our robust regression results show that higher polygenic risk scores for schizophrenia were associated with thinner overall maculae, while controlling for confounding factors (<i>b</i> = -0.17, <i>P</i> = 0.018). Similarly, we found that greater polygenic risk scores for schizophrenia specific to neuroinflammation gene sets were associated with thinner ganglion cell inner plexiform layers (<i>b</i> = -0.10, self-contained <i>P</i> = 0.014, competitive <i>P</i> = 0.02). These results provide new evidence for genetic factors that could predispose individuals to heightened neuroinflammatory responses. Over time, these responses could contribute to neurodegenerative processes such as retinal thinning.

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Publication Details

Journal
Nature Mental Health
Published
2025-04-21
DOI
https://doi.org/10.1038/s44220-025-00414-6
Citations
3
Primary Topic
Genetic Associations and Epidemiology
Type
article
Field-Weighted Citation Impact
5.45

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article

Genetic susceptibility to schizophrenia through neuroinflammatory pathways associated with retinal thinness

Todd Lencz, Philipp Homan, Matthias Kirschner, Steven M. Silverstein et al.
3 citations
Nature Mental Health
Genetic Associations and Epidemiology
5.45
article

Genetic susceptibility to schizophrenia through neuroinflammatory pathways associated with retinal thinness

Todd Lencz, Philipp Homan, Matthias Kirschner, Steven M. Silverstein, José M. Rubio, Flurin Cathomas, Karen B. Schaal, Edna Grünblatt, Lukasz Smigielski, Finn Rabe, Wolfgang Omlor, Foivos Georgiadis, Nils Kallen, Daniel Barthelmes, Brittany Blose, Victoria Edkins
article en
3 citations

Abstract

Schizophrenia is associated with structural and functional changes in the central nervous system, including the most distal part of it, the retina. However, the question of whether retinal atrophy is present before individuals develop schizophrenia or is a secondary consequence of the disorder remains unanswered. Here we address this question by examining the association between polygenic risk scores for schizophrenia and retinal morphologies in individuals without a schizophrenia diagnosis. We used population data for 34,939 white British and Irish individuals from the UK Biobank. Our robust regression results show that higher polygenic risk scores for schizophrenia were associated with thinner overall maculae, while controlling for confounding factors (<i>b</i> = -0.17, <i>P</i> = 0.018). Similarly, we found that greater polygenic risk scores for schizophrenia specific to neuroinflammation gene sets were associated with thinner ganglion cell inner plexiform layers (<i>b</i> = -0.10, self-contained <i>P</i> = 0.014, competitive <i>P</i> = 0.02). These results provide new evidence for genetic factors that could predispose individuals to heightened neuroinflammatory responses. Over time, these responses could contribute to neurodegenerative processes such as retinal thinning.

Nature Mental HealthVol. 3(5)
Feinstein Institute for Medical Research (US), Hofstra University (US), University of Zurich (CH), University Hospital of Bern (CH), University of Rochester Medical Center (US), ETH Zurich (CH), University Hospital of Zurich (CH), Swiss Integrative Center for Human Health (CH), Zucker Hillside Hospital (US), University of Rochester (US)
Novartis Foundation, National Alliance for Research on Schizophrenia and Depression, Universität Zürich, National Institutes of Health, National Institute of Mental Health
Good health and well-being
Openalex Percentile: Top 5%
Genetic Associations and Epidemiology
5.45
DOIOpen Access PDFOpenAlex
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