Correlation between anxiety-depression disorders and brain structural connectivity abnormalities after subarachnoid...

Subarachnoid hemorrhage (SAH) is associated with high incidence of anxiety and depression disorders (27%-54% and 20%-42%, respectively), significantly affecting patient quality of life. However, the pathophysiological mechanisms underlying post-SAH emotional disorders remain poorly understood, limiting targeted therapeutic interventions.

To identify potential biomarkers and therapeutic targets through comprehensive analysis of behavioral, neuroimaging, and inflammatory parameters in a rat SAH model.

We established a rat SAH model using cisternal injection of autologous blood and conducted comprehensive assessments including behavioral tests (elevated plus maze, forced swimming test, sucrose preference test), diffusion tensor imaging (DTI), and inflammatory factor detection. Seventy-two male SD rats were randomly divided into sham and SAH groups, with evaluations performed at multiple time points (1 hour to 72 hours post-hemorrhage). DTI parameters including fractional anisotropy (FA) and apparent diffusion coefficient were measured in limbic-prefrontal circuits. Serum and cerebrospinal fluid inflammatory markers [interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α] were quantified using enzyme-linked immunosorbent assay.

SAH rats exhibited significant anxiety-like and depression-like behaviors at 12 hours, which further deteriorated at 24 hours (open arm time: 30.3 ± 4.7 seconds vs 82.1 ± 8.3 seconds in controls, P < 0.01; immobility time: 136.5 ± 12.7 seconds vs 78.3 ± 9.2 seconds in controls, P < 0.01). DTI analysis revealed progressive white matter microstructural damage, with hippocampus-prefrontal FA values decreasing by 21.8% and amygdala-prefrontal FA values by 20.3% at 24 hours (P < 0.001). Apparent diffusion coefficient values significantly decreased at 12 hours, indicating cellular edema. Inflammatory markers showed marked elevation, with stronger correlations between cerebrospinal fluid IL-1β and behavioral changes (r = 0.72-0.81, P < 0.001).

This study demonstrates that post-SAH emotional disorders result from a temporal cascade involving early neuroinflammation and progressive limbic-prefrontal circuit microstructural damage.