Exploring the neuropathological basis of lateral ventricular enlargement in elderly patients with schizophrenia

AIM: Lateral ventricular enlargement is a robust morphological finding in schizophrenia. However, its characteristics and neuropathological basis in elderly patients remain poorly understood. We aimed to clarify the impact of neuropathologically confirmed neurodegenerative pathologies on lateral ventricular size in elderly patients with schizophrenia and explore other clinical factors potentially influencing ventricular morphology. METHODS: We examined 31 postmortem brains from patients with schizophrenia with an onset age of <40 years. The ventricular-brain ratio (VBR) was measured using computed tomography within 3 years before death. Neuropathological evaluations of various neurodegenerative pathologies were performed according to the current diagnostic criteria, and the relationship between these pathologies, clinical factors, and VBR was examined. RESULTS: Although Alzheimer's disease (AD) pathology increased with age, VBR did not differ significantly according to the severity of AD pathology in elderly patients with schizophrenia. Meanwhile, patients with aging-related tau astrogliopathy (ARTAG) in the medial temporal lobe exhibited a significantly higher VBR than those without. In elderly schizophrenia patients without neurodegenerative diseases, VBR was significantly correlated with illness duration but not with age at computed tomography scanning. CONCLUSION: Lateral ventricular enlargement may occur in elderly patients with schizophrenia regardless of conventional neurodegenerative pathologies, such as AD pathology. This enlargement may be related not only to ARTAG but also to illness duration, suggesting a progressive process intrinsic to schizophrenia. This finding warrants further studies with a detailed histological assessment beyond conventional neurodegenerative pathologies to clarify the basis of ventricular enlargement in schizophrenia.