Longitudinal associations between inflammatory markers at 12-months and three core symptoms of depression at 12- and 24-months after colorectal cancer diagnosis: Results from the population-based PROFILES registry

Purpose
Depression is a heterogeneous construct comprising distinct symptom domains, including motivational anhedonia, consummatory anhedonia, and negative affect, commonly experienced by colorectal cancer (CRC) survivors. Inflammation has been implicated in depression, its association with specific depressive symptom domains in CRC survivors remains insufficiently characterized.

Methods
CRC patients (n = 497) completed questionnaires assessing depressive symptoms 12- and 24-months post-diagnosis: motivational anhedonia (Multidimensional Fatigue Inventory), consummatory anhedonia (Hospital Anxiety and Depression Scale–depression), and negative affect (EORTC QLQ-C30, emotional functioning). Associations between 11 inflammatory markers (CRP, IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-17A, IL-22, IFN-γ, sTNFRI, and sTNFRII) at 12-months and depressive symptoms at 12- and 24-months were examined using linear mixed models.

Results
IL-1β (Est = 0.089, p = 0.003) and IFN-γ (Est = 0.067, p = 0.001) were associated with more consummatory anhedonia symptoms across time, and a small sTNFRI × time interaction was found (Est = 0.000, p = 0.007). Negative affect was associated with IL-1β (Est = −0.496, p < 0.001), IFN-γ (Est = −0.354, p < 0.001), and sTNFRI (Est = −0.003, p < 0.001). A significant IL-1α × time interaction was observed (Est = 0.250, p = 0.038) for motivational anhedonia.

Conclusions
Most consistently IL-1β, IFN-γ, and sTNFRI was associated with greater consummatory anhedonia and more negative affect in CRC survivors. In addition, inflammatory correlates (IL-1α and sTNFRI) of motivational anhedonia and consummatory anhedonia changed over time. These findings suggest that selected inflammatory pathways may contribute to specific depressive symptom domains during colorectal cancer survivorship. Given the exploratory nature of the analyses, replication in independent cohorts is required before clinical implications can be drawn.