Corneal Confocal Microscopy and Brain MRI: Surrogate Markers of Neuronal Pathology in Schizophrenia

Background: Both neurodevelopmental and neurodegenerative processes have been proposed to contribute to the development of schizophrenia. However, there is no validated surrogate marker of neuronal pathology for schizophrenia. To quantify neuronal pathology in subjects with schizophrenia using corneal confocal microscopy (CCM) and brain volumetric MRI. Methods: In this cross-sectional study, subjects with DSM-5 based criteria for schizophrenia enrolled from the Psychiatry Hospital in Qatar and healthy controls were recruited between August 26, 2019 and March 11, 2020. Subjects with schizophrenia were assessed for positive and negative symptoms, and with controls underwent assessment of cognitive function, CCM and brain volumetric MRI. Neuronal pathology was assessed by quantifying corneal nerve fibre density (CNFD), length (CNFL), branch density (CNBD) and CNBD:CNFD ratio, and MRI volume of whole brain, cortical gray matter, ventricle, cingulate gyrus, hippocampus, amygdala, thalamus and entorhinal cortex. Findings: Subjects with schizophrenia (n=36) and controls (n=26) with a comparable age and gender were studied. After adjusting for confounders, subjects with schizophrenia had lower cognitive function (P≤0.01), CNFD, CNFL, CNBD and CNBD:CNFD ratio (P