Higher polygenic risk scores for schizophrenia may correlate with reduced macular thickness, particularly in specific retinal layers, according to a new study.
Previous studies have demonstrated retinal thinning in patients with schizophrenia, as well as “inner retinal atrophy, thinner peripapillary retinal nerve fiber layers and macular ganglion cell and inner plexiform layers, as well as an enlarged cup–disc ratio,” wrote lead study authors Finn Rabe, Lukasz Smigielski, and Philipp Homan, of the University of Zurich, with colleagues. “Intriguingly, thinner retinas have been observed not only in patients but also in unaffected first-degree relatives, suggesting a link to genetic susceptibility to schizophrenia,” they added.
The researchers analyzed retinal morphology using optical coherence tomography (OCT) scans, alongside genetic population data for White British and Irish participants without diagnosed psychotic disorders from the UK Biobank. Exclusions were applied for any history of schizophrenia-related diagnoses (ICD-10: F20–F29), use of antipsychotic medications, eye disease, or poor image quality. Ultimately, 34,939 participants were included in the final analysis cohort.
The researchers found that a one standard deviation (SD) increase in schizophrenia polygenic risk scores (PRS) was associated with a reduction in overall macular thickness by 0.17 μm. Similar associations were found in the outer retina, with a decrease of 0.10 μm per SD increase in PRS.
Higher neuroinflammation-enriched schizophrenia PRS showed a statistically significant association with thinner ganglion cell inner plexiform layers (GCIPL) (b = –0.10, P = .014). C-reactive protein (CRP) partially mediated the relationship between neuroinflammatory PRS and GCIPL thinning, though the indirect effect was small and accounted for approximately 1.28% of the total effect.
The associations were present in participants without clinical schizophrenia, which suggested that retinal alterations may precede disease onset. The partial role of CRP indicated that systemic inflammation may contribute modestly to these effects. However, the study authors noted: “[A] −0.17 µm change represents only about 0.065% of the average overall macular thickness. This extremely small variation is very unlikely to have an impact on visual acuity.”
They concluded: “While our results increase confidence that retinal thinning may be associated with core processes in schizophrenia, further research is crucial to establish the specificity and sensitivity of retinal thinning as a reliable indicator of core degenerative processes in the disorder. Future studies should focus on disentangling the complex interplay between genetic predisposition, environmental factors, and comorbid conditions that can affect retinal health to determine the true potential of retinal changes as a biomarker for schizophrenia-related processes.”
A full list of disclosures can be found in the published research.
Source: Nature Mental Health