Progress in retinal features and underlying mechanisms in schizophrenia

The diagnosis of schizophrenia usually relies on the assessment of clinical symptoms, and the search for objective biomarkers is particularly important for the diagnosis and treatment of the disease. Since the retina can reflect the state of the central nervous system, more and more studies are focusing on retina-specific alterations in neuropsychiatric disorders. This review summarizes recent studies on the retinal nerve layer, vascular characteristics, and electrophysiological features in patients with schizophrenia, showing that patients with schizophrenia often have thinner retinal ganglion cell-inner plexiform layer and retinal nerve fiber layer. The changes in the retinal layers vary in different stages of schizophrenia. Studies of the fundus vasculature in schizophrenic patients have also suggested the presence of altered retinal vascular density and microvascular morphology in schizophrenic patients. Studies of electroretinography suggest that patients in the acute phase of schizophrenia tend to exhibit reduced a-wave amplitudes of cone cells, while those at genetic high risk often show a tendency for reduced b-wave amplitudes of rod cells. However, the current retina-related studies in schizophrenia mostly focus on clinical manifestations, with fewer studies on related mechanisms and inconsistent findings. This review attempts to discuss a variety of potential pathophysiological mechanisms, including trans-synaptic retrograde degeneration hypothesis, neurotransmitter disturbance, genetics, brain structural changes, and metabolism, in the context of the retinal nerve layer, microcirculation, and electrophysiology alterations, in order to provide new insights into the pathophysiological mechanisms and objective biomarkers of schizophrenia.