Depression and inflammation among epidermal growth factor receptor (EGFR) mutant nonsmall cell lung cancer patients

Objective: Depression is highly prevalent in nonsmall cell lung cancer (NSCLC) and is associated with elevated inflammation. However, certain subtypes of driver mutation-associated NSCLC such as epidermal growth factor receptor (EGFR)-mutated NSCLC may be associated with less depression given the differences in their underlying biology and disease trajectories. Biological variables such as inflammation, measured by C-reactive protein (CRP), may provide insight into depression variability in EGFR mutant NSCLC.

Methods: Patients with EGFR mutant and wild-type metastatic NSCLC were evaluated for depression using the Hospital Anxiety and Depression Scale (HADS) on a continuous scale and meeting depression screening criteria (HADS ≥ 8). Inflammation was measured using CRP. A mediation model was created to understand how inflammation mediates EGFR wild-type associated depression.

Results: One hundred out of 120 patients with NSCLC were recruited (83.3% response rate). The 20 participants with EGFR mutant NSCLC had less depression (HADS-D 3.0 versus 5.4) (P < .001), met depression screening criteria less often (P = .047), and exhibited less inflammation (CRP = 0.23 mg/mL versus 2.71 mg/mL) (P < .001) in comparison with EGFR wild-type NSCLC. Multivariate linear regression model revealed that only CRP predicted depression (P = .015) while controlling for age and sex. Mediation analysis found that lower CRP partially mediated less depression in EGFR mutant NSCLC.

Conclusions: EGFR mutant NSCLC is associated with less depression but the relationship is partially mediated by lower CRP-related inflammation, which is a stronger predictor of depression than EGFR status. Depression in lung cancer varies by subtype and is significantly related to inflammation.