Cytokine production capacity in depression and anxiety.
Level 4 - case-series / case-control
Cross-sectional observational comparison of clinical groups and healthy controls.
PubMed 27244234 · doi:10.1038/tp.2016.92
What was done
Baseline data from the Netherlands Study of Depression and Anxiety (NESDA) were analyzed across three groups aged 18–65 years (66% women): current DSM-IV depressive or anxiety disorders (n=591), remitted disorders (n=354), and healthy controls (n=297). Depressive and anxiety symptoms were assessed using the Inventory of Depressive Symptomatology (IDS) and the Beck Anxiety Inventory (BAI). Whole blood was stimulated ex vivo with lipopolysaccharide (LPS) to measure the production capacity of 13 cytokines, and basal plasma levels of C-reactive protein, IL-6, and TNF-α were also measured.
What was found
Unadjusted LPS-stimulated inflammation and basal inflammation were both associated with higher odds of current depressive/anxiety disorders (OR=1.28, P=0.009 and OR=1.28, P=0.001, respectively). After adjusting for lifestyle and health variables, these overall diagnostic associations became non-significant (OR=1.13, P=0.21 for LPS; OR=1.07, P=0.45 for basal). However, specific LPS-stimulated IL-8 production remained associated with both remitted (OR=1.25, P=0.02) and current disorders (OR=1.28, P=0.005). Furthermore, LPS-stimulated inflammation correlated with depressive (β=0.129, P<0.001) and anxiety (β=0.165, P<0.001) symptom severity; after full adjustment, LPS-stimulated cytokine capacity remained significantly associated with anxiety symptom severity (BAI: LPS index, IL-6, IL-8, IL-10, IL-18, MCP-1, MMP2, TNF-β) and specific depressive symptoms (IDS: IL-8, MCP-1, MMP2).
Why it matters
This study shows that innate cytokine production capacity, particularly for IL-8, tracks with anxiety and depressive symptom severity independently of lifestyle and health confounders, suggesting immune reactivity may represent an underlying vulnerability rather than purely a secondary byproduct of unhealthy behaviors.
Limits
The study is cross-sectional, preventing causal conclusions about whether altered cytokine reactivity causes or results from mood pathology. Detailed breakdown of specific medications, exact timing of blood sampling, and potential unmeasured lifestyle confounders were not fully accounted for in the reported abstract.
Cited by
- contradicts In the 9-year Netherlands Study on Anxiety and Depression, serum LPS was the only biomarker associated with 100% of anxiety and depression cases and predicted symptom severity.