Title : Optical Coherence Tomography as a Non-Invasive Biomarker of Clinical and Cognitive Severity in Schizophrenia and Bipolar Disorder

Background: The retina is embryologically derived from the diencephalon and shares structural, vascular, and functional properties with the central nervous system. As it contains unmyelinated neurons, retinal tissue allows direct in vivo visualization of neurobiological processes. Optical coherence tomography (OCT) has emerged as a non-invasive imaging technique capable of detecting subtle retinal structural alterations and may represent a valuable biomarker in neuropsychiatric disorders.

Methods: We conducted a monocentric cross-sectional study including 150 participants: 50 healthy controls and 100 patients diagnosed with stabilized psychotic disorders (schizophrenia and bipolar disorder). All patients had confirmed clinical stability for at least eight weeks prior to inclusion. Spectral-domain OCT was used to measure peripapillary retinal nerve fiber layer (RNFL) thickness and macular ganglion cell–inner plexiform layer (GC-IPL) thickness. Clinical severity was assessed using standardized psychiatric scales, including negative and positive symptom dimensions. Cognitive performance was evaluated using validated neuropsychological tests, particularly processing speed measures, and global functioning was assessed using standardized functional scales. Multivariate analyses were performed to adjust for demographic and ocular confounding factors.

Results: A transdiagnostic gradient of retinal structural alteration was observed. Retinal architecture was preserved in healthy controls, moderately altered in bipolar disorder, and more severely affected in schizophrenia. GC-IPL thickness was significantly lower in patients with schizophrenia compared to those with bipolar disorder (76.8 µm vs 81.2 µm, p = 0.032). In schizophrenia, GC-IPL thinning was significantly correlated with the severity of negative symptoms (r = −0.48, p < 0.001), while no significant association was found with positive symptoms. Additionally, GC-IPL thickness showed strong correlations with cognitive processing speed and global functional outcomes.

Conclusion: Retinal structural changes assessed by OCT reflect a continuum of neurobiological severity across psychotic disorders. GC-IPL thinning is associated with functional and cognitive impairment, supporting the role of OCT as a non-invasive, dimensional biomarker rather than a purely diagnostic marker. These findings highlight the potential utility of OCT for longitudinal monitoring and identification of patients at risk of poor functional outcomes.

Dr. Rhizlane Abdi is an Assistant Professor of Ophthalmology at the Faculty of Medicine and Pharmacy, Sultan Moulay Slimane University, Beni Mellal, Morocco. She is a clinician-scientist with a particular interest in retinal imaging, optical coherence tomography, and neuro-ophthalmology. Her research focuses on the retina as a window to central nervous system disorders, exploring retinal structural biomarkers in neuropsychiatric and neurocognitive diseases. She is actively involved in interdisciplinary research bridging ophthalmology, neuroscience, and psychiatry, with the aim of improving non-invasive diagnostic and monitoring strategies.