Looking through the eye to understand the brain
What first drew me to psychotic research was a deceptively simple frustration: we cannot see what is wrong. Unlike a broken bone on an X-ray or a tumor on a scan, the changes in the brain that underlie psychosis are largely invisible to us in living humans. Brain scans exist, of course, but they are expensive, demanding, and often distressing for patients who are already struggling. When a person experiences their first episode of psychosis, clinicians are largely working blind. They lack reliable biological markers to guide them on who is at highest risk, when to intervene, or how well a treatment is working.
The eye as a window to the brain
So we and others started asking a different question. What if we didn't have to look at the brain directly? The retina, which is this thin layer at the back of your eye that captures light, is actually a direct extension of the brain. Developmentally, it grows from the same tissue. It shares the same cell types, the same molecular machinery, and many of the same vulnerabilities. And critically, we can image it in a few minutes with a device called an optical coherence tomography (OCT) scanner, at a very competitive cost. And this cool thing is this device can be found in many eye clinics and hospitals already.
My research over the past several years, conducted at the Psychiatric University Hospital Zurich with Prof. Philipp Homan and a talented group of international collaborators, has focused on one central question: can the retina tell us something about a person's risk for schizophrenia, before symptoms even appear?
The answer is yes, and go deeper than we expected. In two studies published in Nature Mental Health and JAMA Psychiatry, my colleagues and I examined data from over 36,000 people in the UK Biobank — a large health research database of people without a schizophrenia diagnosis. We looked at their genetic risk for schizophrenia (calculated from their DNA) and compared it to the microscopic thickness of their retinal layers. People with higher genetic risk for schizophrenia had subtly but measurably thinner retinas — specifically in a layer called the ganglion cell inner plexiform layer. This layer contains the synaptic connections of a type of retinal cell called amacrine cells - interneurons that process signals within the eye. Crucially, these same cells turned out to harbor a striking concentration of schizophrenia risk genes, and this finding held up across humans, monkeys, and mice, and even in fetal retinal tissue, suggesting it traces back to early brain development.
In other words: the genetic "signature" of schizophrenia is written not just in the brain, but probably also in the eye, specifically in cells whose job involves synaptic communication. This provides some of the further evidence that schizophrenia might be a disease of the synapse (i.e. the connection point between brain cells), and that this disruption begins long before a person ever experiences a psychotic episode.
Why this matters for patients and families?
Imagine someone showing some early warning signs that worry their family, friends or partners. Early intervention is known to dramatically improve outcomes. This means a shorter period of untreated psychosis means better cognitive functioning, better social integration, more autonomy again. But today, identifying who among those at-risk individuals will actually go on to develop psychosis is still very difficult. We believe, we - together with others - laid the foundations with our retina research for future studies that will test how informative retinal changes are for early detection, risk stratification and treatment monitoring. If fruitful, a simple eye scan at the first appointment together with some questions by the psychiatrist could be all to determine someone’s brain health.
