Associations between skeletal muscle-to-visceral fat ratio and depression symptom severity among cancer survivors: an examination of mediation pathways using the National Health and Nutrition Examination Survey (NHANES) 2011–2018

Background Depression is highly prevalent among individuals diagnosed with cancer and associated with reduced wellbeing, physical function, and increased mortality risk. Emerging evidence suggests that physiological factors such as body composition and systemic inflammation are associated with symptom severity and may help identify individuals diagnosed with cancer who are at greater risk of depression. This study examined whether the skeletal muscle-to-visceral fat ratio (SVR) is associated with depressive symptom severity in cancer survivors, and whether inflammatory biomarkers and behavioral factors mediate this relationship. Methods This cross-sectional analysis of 541 adult cancer survivors, obtained from National Health and Nutrition Examination Survey (NHANES, 2011–2018), examined associations between body composition, inflammation, and depression symptom severity. Body composition was indexed by SVR (DEXA-derived), inflammation was assessed via white blood cell (WBC) count and high sensitivity C-reactive proteins (HS-CRP), and depression symptom severity was measured using the Patient Health Questionnaire-9 (PHQ-9). Complex sample generalized linear models examined associations between predictors and PHQ-9, followed by mediation analyses testing WBC, HS-CRP, and physical activity as mediators. Results SVR was significantly and inversely associated with PHQ-9 scores in unadjusted ( b = − 0.501, 95% CI − 0.937, − 0.064, p = 0.025) and partially adjusted models ( b = − 0.590, 95% CI − 1.102, − 0.077, p = 0.025), attenuating after full adjustment ( b = − 0.423, 95% CI − 0.980, 0.134, p = 0.134). WBC showed no association with PHQ-9 at any stage, while HS-CRP showed a similar pattern to SVR. SVR was significantly associated with WBC and HS-CRP, mediation analyses found no significant indirect effects through WBC/physical activity. Pathway estimates were not fully identified due to a hypothesized causal link between physical activity and WBC. Conclusion Favorable body composition was associated with lower depressive symptom severity and biomarkers of inflammation in this population of cancer survivors. These relationships attenuate after adjustment. Neither HS-CRP nor physical activity/WBC showed clear evidence of mediating this association, suggesting that other or more complex mechanisms underpin the link between body composition and depression severity in cancer survivors.