Progression from selective to general involvement of hippocampal subfields in schizophrenia

Abstract

Volume deficits of the hippocampus in schizophrenia have been consistently reported. However, the hippocampus is anatomically heterogeneous; it remains unclear whether certain portions of the hippocampus are affected more than others in schizophrenia. In this study, we aimed to determine whether volume deficits in schizophrenia are confined to specific subfields of the hippocampus and to measure the subfield volume trajectories over the course of the illness. MRI scans were obtained from Dataset 1: 155 patients with schizophrenia (mean duration of illness of 7 years) and 79 healthy controls, and Dataset 2: an independent cohort of 46 schizophrenia patients (mean duration of illness of 18 years) and 46 healthy controls. In addition, follow-up scans were collected for a subset of Dataset 1. A novel, automated method based on an atlas constructed from ultra-high resolution, post-mortem hippocampal tissue was used to label 7 hippocampal subfields. Significant cross-sectional volume deficits in the CA1, but not of the other subfields, were found in the schizophrenia patients of Dataset 1. However, diffuse cross-sectional volume deficits across all subfields were found in the more chronic and ill schizophrenia patients of Dataset 2. Consistent with this pattern, the longitudinal analysis of Dataset 1 revealed progressive illness-related volume loss (~ 2 to 6% per year) that extended beyond CA1 to all of the other subfields. This decline in volume correlated with symptomatic worsening. Overall, these findings provide converging evidence for early atrophy of CA1 in schizophrenia, with extension to other hippocampal subfields and accompanying clinical sequelae over time