Interleukin-6 and tumor necrosis factor alpha as predictive biomarkers for depression and mania in young adults with depressive and bipolar disorder.

Inflammation has been increasingly implicated in the pathophysiology of mood disorders, yet the role of peripheral inflammatory markers in prospectively predicting symptom trajectories remains understudied, particularly in clinical populations. This study examined whether baseline levels and baseline to endpoint changes in inflammatory markers are associated with depressive and manic symptom trajectories in young adults (ages 18-25) with lifetime diagnosis of major depressive disorder (MDD) or bipolar disorder (BD). Of note, the sample did not include individuals in acute mania phase of BD (baseline YMRS = 4.89). 55 participants (47 females) underwent blood draws at baseline and endpoint and completed semi-weekly mood assessments throughout a six-month period. Linear mixed-effects models examined associations between C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and mood symptoms over time, adjusting for age, BMI, and gender. At baseline, IL-6 was positively associated with depressive symptom severity (β = 0.30, uncorrected p = .03) and predicted more persistent depressive symptoms over time (β = 0.09, uncorrected p = .03). Surprisingly, increases in IL-6 were associated with reductions in depressive symptom (β = -0.09, adjusted p = .03). Baseline TNF-α predicted decline in mania symptoms (β = -0.11, adjusted p = .04) and increases in TNF-α were associated with reduced mania severity over six months (β = -0.32, uncorrected p = .04). These findings suggest that IL-6 and TNF-α may differentially relate to depression and mania and underscore the clinical potential of inflammatory markers in identifying individuals at risk for persistent mood symptoms. This hypothesis-generating study will inform future research focused on replication with denser inflammation sampling and larger, more diverse samples of young adult clinical populations.