Inflammation and impulsivity pathways in non-suicidal self-injury among bipolar disorder: A 24-week longitudinal cohort study.

Background: Non-suicidal self-injury (NSSI) is frequently observed in patients with bipolar disorder (BD), increasing the risk of suicide. However, the longitudinal mechanisms linking inflammatory, cognitive control deficits, and impulsive to NSSI remain unclear.

Methods: We conducted a 24-week longitudinal study involving 400 participants (200 BD patients with NSSI, 100 BD patients without NSSI, and 100 healthy controls), with assessments at baseline (T0), Week 12 (T1), and Week 24 (T2). Key measures included inflammatory markers (IL-6, CRP), cognitive tasks (Go/No-Go, DSST), impulsivity (BIS-11), and clinical features. Analyses involved linear mixed models, hierarchical regressions, structural equation modeling (SEM), and time-varying latent growth modeling (LGM).

Results: Across a 24-week follow-up, the BD + NSSI group showed persistently elevated IL-6 and CRP levels, with IL-6 increasing significantly over time (p < 0.01). Baseline structural equation modeling (SEM) revealed a significant indirect pathway from CRP to NSSI severity via impaired cold inhibitory control (Go/NoGo task: β = 0.048, p < 0.001), while the hot inhibition pathway (CRP → DSST→NSSI) was statistically non-significant and temporally unstable. Time-varying LGM further indicated that cold inhibition mediated the effects of both CRP and IL-6 on NSSI in the later phase (T2), supporting a delayed but progressive inflammatory impact on executive control. Exploratory moderation analyses showed that high impulsivity attenuated the indirect inflammation-NSSI pathway, suggesting a distinct impulsivity-driven subtype. These findings support a dual-pathway framework for NSSI in bipolar disorder, involving both chronic inflammation-related cognitive dysfunction and trait impulsivity mechanisms.

Conclusion: These findings support a temporally distinct dual-pathway model in which acute CRP-related and chronic IL-6-mediated inflammation contribute to NSSI via cognitive and affective mechanisms in bipolar disorder.