Inflammatory biomarkers and white matter microstructure in borderline personality disorder: A cross-sectional study

Background: Borderline personality disorder (BPD) is a severe psychiatric condition with unclear neurobiology. Inflammation and white matter (WM) abnormalities have been implicated in BPD. We aimed to compare WM microstructure and inflammatory biomarkers between Individuals with BPD and healthy controls (HC), and to test their relationship. Methods: In a cross-sectional study, female Individuals with BPD (n = 40) and age-matched female HCs (n = 37) were assessed. We measured serum levels of pro-inflammatory cytokines (e.g., interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) using high-sensitivity assays. Diffusion tensor imaging was used to quantify fractional anisotropy (FA) in major WM tracts. Group differences were evaluated with appropriate tests and Holm's correction. Associations between cytokines and FA were examined with linear regression adjusted for confounders. Results: Individuals with BPD had significantly higher IL-6 and CRP levels than HCs (padj = 0.006 for both). However, after adjustment for BMI and smoking status, intergroup differences in inflammatory markers were attenuated. They also showed lower FA in the left superior longitudinal fasciculus (SLF) I and left superior thalamic radiation (STR) compared to HCs (padj < 0.05). IL-6 and CRP levels were inversely correlated with FA in the left SLF I (p < 0.05) after controlling for confounders, indicating greater inflammation was associated with reduced WM integrity. No significant FA correlation was found for the STR. Conclusions: BPD is associated with elevated inflammatory markers and compromised fronto-thalamic WM integrity. The inverse relationship between cytokine levels and SLF integrity suggests an inflammatory contribution to BPD's pathophysiology. These findings offer novel insight linking immune dysregulation to brain structural connectivity in BPD.