Impact of Post-Traumatic Stress Disorder Duration on Volumetric and Microstructural Parameters of the Hippo-Campus, Amygdala, and Prefrontal Cortex: A Multiparametric Magnetic Resonance Imaging Study with Correlation Analysis

<b>Introduction.</b> Post-traumatic stress disorder (PTSD) remains one of the best-described yet also one of the most heterogeneous psychiatric disorders. Existing neuroimaging studies point to key changes in the hippocampus, amygdala, and prefrontal cortex, but the role of PTSD duration in modulating these changes has not been fully explained. <b>Objectives</b>. The aim of the study was to assess the impact of PTSD duration (≤5 years vs. >5 years) on volumetric and microstructural brain parameters, using multiple Magnetic Resonance Imaging (MRI) sequences (3D Ax BRAVO, Cube T2 FLAIR, Diffusion Tensor Imaging-DTI) and a set of macroscopic morphometric measurements. <b>Methods</b>. The study included 92 participants: 33 with PTSD of ≤5 years duration, 31 with PTSD > 5 years, and 28 healthy controls. Volume and diffusion parameters of six Regions of Interest (ROIs) (hippocampus, amygdala, prefrontal cortex-right and left) were evaluated, along with their associations with nine brain measurements (including width of the third ventricle, corpus callosum, and lateral fissures). Statistical analyses included the Kruskal-Wallis test with Compact Letter Display (CLD) correction and Spearman correlations. <b>Results</b>. (1) The volume of the right hippocampus was significantly greater in the PTSD > 5 years group compared to controls (<i>p</i> = 0.006), with intermediate values in the PTSD ≤ 5 years group. (2) In the left amygdala, an increase in Fractional Anisotropy (FA) and related anisotropy measures was observed in PTSD > 5 years (<i>p</i> ≈ 0.02), without volumetric changes. (3) In the left prefrontal cortex, diffusivity was reduced in PTSD ≤ 5 years (<i>p</i> = 0.035), partially normalizing after >5 years. (4) Correlation analysis revealed that chronic PTSD strengthens the negative associations between hippocampal microstructure and both the width of the amygdala and the interhemispheric fissure, indicating a progressive reorganization of fronto-limbic networks. <b>Conclusions</b>. PTSD induces region- and time-dependent brain changes: (a) adaptive/hypertrophic protection of the right hippocampus after many years of illness, (b) cumulative microstructural reorganization of the left amygdala, and (c) transient impairment of diffusion in the left prefrontal cortex in early PTSD. These findings highlight the necessity of considering the temporal dimension in planning therapeutic interventions and in the search for biomarkers of PTSD progression.