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Subfield-specific hippocampal microstructural alterations in schizophrenia: A high-resolution DTI study

Year: 2025

Type: article

Abstract: Subfield-specific microstructural alterations of the hippocampus and their clinical relevance remain poorly characterized. This study investigated hippocampal subfield-specific microstructural alterations in schizophrenia (SCZ) patients using high-resolution diffusion tensor imaging (DTI). Forty-six SCZ patients and 55 healthy controls underwent 3.0 T MRI scanning using high-resolution T1-weighted imaging and DTI (0.9-mm isotropic resolution), which was employed to quantify volumes and microstructural integrity across hippocampal subfields, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Volumetric and DTI metrics were compared and correlated with clinical features. Key findings revealed significant microstructural changes in nine of 16 hippocampal subfields in patients. The predominant pattern featured increased MD, AD, and RD, alongside heterogeneous FA; however, a minority of subfields exhibited divergent trends ( F = 6.19–19.38, P FDR ≤0.001–0.03). Subfield-specific volume reductions were not statistically significant after correction. Notably, CA2/3 exhibited robust diffusivity alterations, significantly correlated with semantic fluency scores ( r = −0.35 – -0.34, P = 0.04). These results underscored the subfield-specific hippocampal pathology in SCZ and imply that microstructural compromise reflected in DTI parameters may offer greater sensitivity than volumetric changes and precede macroscopic atrophy. Critically, hippocampal microstructural alterations, especially in CA2/3, may be associated with specific cognitive deficits in SCZ. • Microstructural alterations observed in 9/16 hippocampal subfields in SCZ. • Microstructural changes preceded volumetric reductions in SCZ. • CA2/3 diffusivity changes linked to semantic fluency deficits in SCZ.

Source: Schizophrenia Research

DOI: 10.1016/j.schres.2025.10.016