In a Nature Mental Health study, an international team of researchers led by the University of Zurich have uncovered a genetic connection between schizophrenia and retinal thinning, suggesting the eye could offer a unique and accessible window into early brain changes associated with the disorder.
Analyzing data from nearly 35,000 healthy individuals in the UK Biobank, the team found that individuals with higher polygenic risk scores (PRS) for schizophrenia exhibited significantly thinner macular tissue, even in the absence of any clinical diagnosis. The study went further, identifying a particularly strong association between schizophrenia-linked genetic variants involved in neuroinflammatory pathways and thinning in the ganglion cell inner plexiform layer (GCIPL).
The study also found that elevated levels of C-reactive protein (CRP) – a marker of systemic inflammation – partially mediated the relationship between neuroinflammatory gene-based PRS and GCIPL thinning. While CRP explained only a small fraction of the effect, this finding supports the idea that inflammation could be a key biological link between schizophrenia risk genes and structural brain changes.
Unlike previous research, which focused on patients already diagnosed with schizophrenia, this study focused on preclinical markers in healthy individuals, helping to isolate the influence of genetic predisposition from environmental and medication-related confounders.
The researchers emphasize that while retinal thinning is unlikely to directly affect vision at this small scale, it may reflect broader neurodegenerative processes relevant to schizophrenia’s development. Furthermore, the retina’s accessibility and its shared embryonic origin with the brain make it an appealing candidate for early detection biomarkers for the condition.
By revealing that retinal structure can reflect the genetic architecture of schizophrenia – particularly through inflammatory mechanisms – the study opens the door to new, non-invasive approaches for identifying at-risk individuals long before symptoms emerge, the authors say.
