The retina is as a sensitive indicator of central nervous system integrity, which can be efficiently examined with optical coherence tomography. Using data from the UK Biobank, we computed normative models of age-related retinal thinning in a mid-to-late life control sample (N = 56 677) to estimate retinal deviations in schizophrenia (N = 178), bipolar disorder (N = 266), and major depression (N = 105). We hypothesized that retinal thickness deviations from normative age-related thinning would parallel brain alterations, with SZ showing the most pronounced changes. Across diagnostic groups, significant negative deviations, driven by schizophrenia and to a lesser extent bipolar disorder, were found in macular thickness and ganglion cell-interstitial plexiform layer thickness but not in retinal nerve fibre layer thickness. While female individuals appeared to show stronger deviations overall, this effect did not reach statistical significance. Using the largest optical coherence tomography sample to date, we demonstrate transdiagnostic deviations in retinal thickness, predominantly in schizophrenia and bipolar disorder, but not major depression. Our findings underscore the utility of normative modeling for precise, personalized assessments in psychiatric disorder endophenotypes, particularly retinal thickness.

The authors have declared no competing interest.

This study did not receive any funding

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All data utilized in this study is publicly available at the UK Biobank (http://www.ukbiobank.ac.uk/). All code will be made freely available after publication to ensure reproducibility at https://github.com/homanlab