Table 2.

Inflammatory biomarkers commonly used in depression research

Inflammatory biomarker	Advantages	Disadvantages	Comments
CRP	Routinely assayed by local clinical labs No diurnal variation > 5 (mg/L) risk stratification value suggested by literature (17)	Less responsive to acute stress than cytokines Less reliably linked to psychosocial stressors compared with other markers	Synthesized in the liver, secreted in response to IL-6 15–19 hour half-life Well-established risk stratification values and clear clinical relevance for cardiovascular disease
IL-6	Biomarker most strongly associated with depression (3) Most widely used inflammatory biomarker in depression research because of its sensitivity Responsive to both acute and chronic stressors	Limited availability in local clinical labs Values dependent on assay type and assay procedures within and between labs (4) No risk stratification norms, values not comparable across labs Values can differ 3 to 50+ fold based on diurnal variation, recent sleep, and the duration and intensity of recent exercise (191)	Can be ordered through national labs (e.g., Quest, LabCorp) Half-life is <6 hours Rises within ~30–45 minutes of lab stressors; catecholamines increase IL-6 levels Fasting morning blood draws reduce variability
TNF-α	Positively associated with depression in clinical and community samples (3) Reliably elevated in MDD (4)	Limited availability in local clinical labs Values dependent on assay type and assay procedures within and between labs(4) No risk stratification norms, values not comparable across labs	Can be ordered through national labs Fasting morning blood draws reduce variability Targeted by cytokine inhibitor treatments
IL-1ra	Positively associated with depression in clinical and community samples (3)	Limited availability in local clinical labs Values dependent on assay type and assay procedures within and between labs (4) No risk stratification norms, values not comparable across labs	Can be ordered through national labs Fasting morning blood draws reduce variability
IL-1β	Positively associated with depression in a meta-analysis of clinical and community samples (3)	Not associated with MDD in a meta-analysis of MDD studies (4) Highly skewed distribution, many samples below limits of detection Limited availability in local clinical labs Values dependent on assay type and assay procedures within and between labs (4) No risk stratification norms, values not comparable across labs	Can be ordered through national labs Fasting morning blood draws reduce variability

CRP= C-reactive protein; IL-1β=interleukin 1 beta; IL-1ra=interleukin 1 receptor antagonist; IL-6=interleukin 6; TNF-α = tumor necrosis factor alpha