Temporal dynamics of inflammatory, platelet, and neurotrophic markers during social stress in relation to suicidal ideation and suicide attempt history

Abstract

Interpersonal stress is a major precipitant of suicidal ideation (SI) and suicide attempts (SA), yet the underlying biological mechanisms remain unclear. This study examined dynamic plasma concentrations of inflammatory, platelet activation, and neurotrophic markers during acute social stress in 76 depressed women (mean age: 39.7 ± 1.39 years) with and without SA history or recent SI. Participants underwent the Trier Social Stress Test, with biomarkers measured at five time points before, during, and after the stressor. Covariate-adjusted growth curve models and area under the curve analyses were applied. SI was associated with elevated overall TNF-α levels (0.82 ± 0.05 vs. 0.61 ± 0.05, p = 0.039). Participants without SI showed cubic trajectories in TNF-α (t₂₂₈ = 4.76, p < 0.001) and MIP-1β (t₂₃₅ = 2.12, p = 0.035), and quadratic trajectories in platelet markers TSP-1 (t₂₇₄ = −2.42, p = 0.016), PF-4 (t₂₇₄ = −2.25, p = 0.025), and NAP-2 (t₂₇₄ = −2.43, p = 0.016), which were absent in participants with SI. Cubic patters in inflammatory responses were also observed in participants without SA history, but not in suicide attempters (TNF-α: t₂₂₈ = 3.15, p = 0.030; MIP-1β: t₂₃₅ = 2.74, p = 0.007). Meanwhile, participants with SI or SA, but not those without, showed a linear BDNF increase (t₂₇₅ = 2.39, p = 0.017; t₂₇₅ = 2.28, p = 0.024, respectively). These findings suggest that SI and SA may be associated with impaired dynamic immune-inflammatory, platelet, and neurotrophic systems responses to acute interpersonal stress, reflecting systemic biological rigidity.