Fornix microalterations associated with early trauma in panic disorder

Background: It is well accepted that panic disorder (PD) is associated with early trauma, and that the limbic systems are one of the main structures involved in PD pathophysiology. However, previous studies have not addressed the relationship between early trauma and major limbic white-matter (WM) structures in PD. Methods: Participants enrolled in the study consisted of 53 right-handed patients with PD and 21 healthy controls (HC). The Early Trauma Inventory Self Report-Short Form (ETISR-SF), Anxiety Sensitivity Inventory-Revised (ASI-R), and the Albany Panic and Phobia Questionnaire (APPQ) were applied in the study. Tract-based spatial statistics were used for diffusion tensor magnetic resonance imaging analysis. Results: Among the patients with PD, the fractional anisotropy (FA) values of the fornix body in major limbic WM regions showed significant negative correlation with the ETISR-SF total score, while the scores of mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in the same region of fornix had significant positive correlation with those scores (p < 0.05; FWE corrected). Further significant correlation was observed between these four scores and the measures of symptom severity in PD, such as that in ASI-R and APPQ in the same region. Limitations: Recall bias is possible in evaluating early trauma in the participants. Conclusions: The current study suggests a significant association of early trauma with the fornix body possibly through axons and myelin disruptions within major limbic structures in PD. A multi-centered large sample will be needed to confirm these findings.