Retina in Clinical High-Risk and First-Episode Psychosis

Background and Hypothesis: Abnormalities in the retina are observed in psychotic disorders, especially in schizophrenia. Study Design: Using spectral-domain optical coherence tomography, we investigated structural retinal changes in relatively metabolic risk-free youth with clinical high-risk (CHR, n = 34) and first-episode psychosis (FEP, n = 30) compared with healthy controls (HCs, n = 28). Study Results: Total retinal macular thickness/volume of the right eye increased in FEP (effect sizes, Cohen's d = 0.69/0.66) and CHR (d = 0.67/0.76) compared with HCs. Total retinal thickness/volume was not significantly different between FEP and CHR. Macular retinal nerve fiber layer (RNFL) thickness/volume of the left eye decreased in FEP compared with HCs (d = -0.75/-0.66). Peripapillary RNFL thickness was not different between groups. The ganglion cell (GCL), inner plexiform (IPL), and inner nuclear (INL) layers thicknesses/volumes of both eyes increased in FEP compared with HCs (d = 0.70-1.03). GCL volumes of both eyes, IPL thickness/volume of the left eye, and INL thickness/volume of both eyes increased in CHR compared with HCs (d = 0.64-1.01). In the macula, while central sector thickness/volume decreased (d = -0.62 to -0.72), superior outer (peri-foveal) sector thickness/volume of both eyes increased (d = 0.81 to 0.86) in FEP compared with HCs. Conclusions: The current findings suggest that distinct regions and layers of the retina may be differentially impacted during the emergence and early phase of psychosis. Consequently, oculomics could play significant roles, not only as a diagnostic tool but also as a mirror reflecting neurobiological changes at axonal and cellular levels.