Inflammatory factors and cerebral hemodynamics in patients with first-episode and recurrent depression

Inflammation and neurovascular dysfunction play a fundamental role in depression pathogenesis. We aim to investigate potential differences in neuroimmune interactions across disease stages (first-episode depression [FED] and recurrent depression [RED]) by simultaneously assessing peripheral inflammatory markers and task-related cerebral hemodynamics. A total of 30 patients with FED, 35 with RED, and 30 demographically matched healthy controls (HC) were recruited. Symptom severity was assessed using the 24-item Hamilton Depression Rating Scale. Serum levels of pro-inflammatory cytokines, including interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α), and anti-inflammatory cytokines (IL-4, IL-10) were measured. Functional near-infrared spectroscopy during a verbal fluency task was used to record oxyhemoglobin (HbO 2 ) dynamics in prefrontal and temporoparietal regions. Associations between cytokine levels and HbO 2 responses were analyzed. Both FED and RED groups exhibited significantly higher IL-6, CRP, and TNF-α levels and lower anti-inflammatory cytokine levels than did HCs, with no significant differences between FED and RED. During task-related activation, both patient groups showed significantly reduced HbO 2 responses in the left dorsolateral prefrontal cortex (DLPFC_L) and left somatosensory cortex compared to HC, with no significant difference between FED and RED. In the FED group, TNF-α levels positively correlated with HbO 2 activation in DLPFC_L, while in the RED group, they negatively correlated with activation in the right dorsolateral prefrontal cortex, right frontal pole area, and right temporal cortex. Recurrent depression may involve a distinct neuroimmune interaction pattern, offering potential neuroimmune biomarkers for understanding mechanisms underlying relapse. • Inflammation and brain function compared in first and recurrent depression. • Functional near-infrared spectroscopy (fNIRS) was used during verbal fluency task. • Both groups had high IL-6, C-reactive protein, and tumor necrosis factor-α (TNF-α). • fNIRS showed reduced activation in dorsolateral prefrontal and somatosensory cortex. • TNF-α correlated with brain activation differently in first vs. recurrent cases.