A new study published in Nature Mental Health has found that people with a higher genetic risk for schizophrenia tend to have thinner retinas, even if they do not have the disorder. Using data from nearly 35,000 healthy individuals, the researchers showed that this association was especially pronounced in areas of the retina involved in neural signaling and inflammation, raising the possibility that the eyes could serve as a subtle indicator of schizophrenia-related biology long before symptoms appear.
Schizophrenia is a severe psychiatric condition that affects how a person thinks, feels, and behaves. It often involves hallucinations, delusions, and social withdrawal. The disorder is thought to arise from a complex combination of genetic, developmental, and environmental factors, but researchers still don’t fully understand what biological processes lead to its onset. There are currently no reliable biological tests that can predict who will go on to develop schizophrenia, especially during early stages when interventions may be most effective.
One area that has recently drawn attention is the retina—the light-sensitive tissue at the back of the eye that is part of the central nervous system. Previous studies have found that people with schizophrenia tend to have thinner retinal layers and signs of degeneration. However, because those studies were conducted after diagnosis, it was unclear whether these changes were a result of the disease, the medication used to treat it, or other health complications. This left open the question of whether retinal thinning could be a sign of underlying risk before symptoms begin.
“Schizophrenia is a complex disorder, and we still lack reliable biological markers for early detection or risk stratification,” said study author Philipp Homan, vice chair and chief physician at the Department of Adult Psychiatry and Psychotherapy at the University of Zurich.
“There has been increasing evidence linking immune pathways to schizophrenia, and we were interested in whether these immune-related genetic risks might show up as measurable changes in the body, particularly in the retina, which is accessible and reflects central nervous system processes.”
To address this, researchers at the University of Zurich and colleagues used genetic and retinal imaging data from the UK Biobank, a large database of health information from more than 500,000 volunteers in the United Kingdom. They focused on 34,939 adults of British or Irish ancestry who had no known history of schizophrenia or related disorders. They excluded anyone with eye diseases, diabetes, or other conditions that could affect retinal health, as well as individuals taking antipsychotic medications. This allowed the team to isolate the effects of genetic risk for schizophrenia in a healthy population.
For each participant, the team calculated a polygenic risk score for schizophrenia. This score represents a person’s overall genetic risk based on many small variations in their DNA that have been linked to the disorder in previous studies. They then examined retinal images collected using optical coherence tomography, a noninvasive technique that creates detailed cross-sectional images of the retina. The researchers focused on the macula, a central part of the retina that is densely packed with nerve cells and plays a key role in vision.
After adjusting for factors such as age, sex, smoking status, blood pressure, and image quality, the researchers found that individuals with higher polygenic risk scores had thinner retinas. Specifically, each standard deviation increase in genetic risk for schizophrenia was associated with a reduction of 0.17 microns in macular thickness. While this is a very small change—less than one-tenth of one percent of the average retinal thickness—it was consistent and statistically significant.
The researchers also explored whether genetic risk related to specific biological pathways might be linked to changes in particular retinal layers. The strongest association was found for genes involved in neuroinflammation, or immune system activity in the brain. People with higher genetic risk for schizophrenia within this pathway had thinner ganglion cell inner plexiform layers—regions of the retina responsible for early-stage neural signal processing. Further analysis suggested that this relationship may be partly explained by elevated levels of C-reactive protein, a marker of systemic inflammation, though the effect was modest.
“We were somewhat surprised by the specificity of the association,” Homan told PsyPost. “The genetic risks linked to immune function, rather than schizophrenia risk in general, seemed to be more clearly associated with retinal thinning. This points toward a more targeted biological pathway.”
These findings suggest that retinal thinning, especially in certain inner layers of the retina, could be an early marker of genetic vulnerability to schizophrenia. Importantly, this thinning was observed in people without any diagnosis or treatment for the disorder, suggesting it reflects underlying risk rather than consequences of illness or medication.
The researchers note that their findings build on prior studies showing that schizophrenia can affect the brain’s physical structure, including reductions in gray matter volume. The retina, as an accessible part of the central nervous system, may offer a window into these changes.
“Our results suggest that some genetic risks for schizophrenia, especially those involving immune and inflammatory pathways, are associated with a thinner retina,” Homan said. “This implies that the retina could potentially serve as a non-invasive readout of the brain and its immune changes relevant for psychiatric risk, though this is still early-stage research.”
To test the robustness of their results, the researchers used a variety of statistical techniques, including robust regression models designed to handle data with outliers or uneven variance. They also ran analyses using multiple sets of genetic data to ensure their results were not dependent on a single model. Across these approaches, the association between higher genetic risk for schizophrenia and thinner retina remained consistent.
The study’s large sample size and rigorous exclusion criteria are major strengths. By focusing only on individuals without psychiatric diagnoses or eye diseases, the researchers were able to isolate subtle effects that might otherwise be masked by illness-related factors. They also included detailed information about health and lifestyle, allowing them to account for potential confounding variables.
Still, the researchers acknowledge some limitations. The UK Biobank is not fully representative of the general population. Participants tend to be healthier and less diverse than the broader public, and individuals with schizophrenia are underrepresented. This means the results may not apply equally to other groups, including non-European populations or people with more complex health histories.
“It’s important to realize that we studied healthy people, because we were interest in genetic risk, not manifest disorder,” Homan said.
The measured effect sizes were also extremely small. Although statistically significant, the differences in retinal thickness associated with genetic risk for schizophrenia are unlikely to have any practical effect on vision. At the same time, even small changes can be informative when studied across thousands of individuals, especially when they help uncover biological pathways involved in mental health.
Another important caveat is that polygenic risk scores, while useful for research, are not currently precise enough to predict whether any one person will develop schizophrenia. These scores capture only a portion of the total genetic risk, and they do not account for environmental influences, life stress, or early brain development, all of which are believed to contribute to the disorder.
“These findings are based on population-level data and do not immediately translate to individual diagnosis or prediction,” Homan explained. “The associations are statistical, and many other factors affect retinal thickness. More research is needed before this could inform clinical practice.”
The researchers suggest that future work should explore how environmental factors such as smoking, diet, and stress interact with genetic risk to influence retinal health. Longitudinal studies could help determine whether retinal thinning progresses over time in those at higher risk, or whether it stabilizes. Investigating these changes across different stages of development—from childhood to adulthood—could provide insight into how early in life these differences emerge.
“An interesting next step is to test whether these retinal changes actually help identify people at risk for schizophrenia before symptoms emerge, and whether interventions targeting immune pathways can modify these retinal or brain changes,” Homan said. “This work builds on a broader effort to find neural correlates of mental illness that can be measured easily and early. The retina is promising, but it will take larger and more diverse studies to establish its role.”
The study, “Genetic susceptibility to schizophrenia through neuroinflammatory pathways associated with retinal thinness,” was authored by Finn Rabe, Lukasz Smigielski, Foivos Georgiadis, Nils Kallen, Wolfgang Omlor, Victoria Edkins, Matthias Kirschner, Flurin Cathomas, Edna Grünblatt, Steven Silverstein, Brittany Blose, Daniel Barthelmes, Karen Schaal, Jose Rubio, Todd Lencz, and Philipp Homan.
