Nonlinear Relationship Between Neutrophil to Lymphocyte Ratio, Depression

The relationship between neutrophil to lymphocyte ratio (NLR) and depression severity appears to be nonlinear, according to study results published in Journal of Psychosomatic Research.

Researchers from the 967^th Hospital of PLA Joint Logistics Support Force in China sourced data for this study from the National Health and Nutrition Examination Survey (NHANES), which was a nationally representative survey conducted by the Centers for Disease Control and Prevention (CDC). The incidence of depression was compared with NLR between 2005 and 2016. Clinically relevant depression was defined as Patient Health Questionnaire (PHQ-9) score of 10 or greater.

The study population comprised 22,207 individuals (mean age, 44.43 years; 51.05% women; 67.18% White). Among the study population, 11.4% were receiving antidepressants, and NLR was 2.14. Stratified by NLR quartiles, individuals in quartiles 1 (NLR<1.43; n=5497), 2 (NLR≥1.44-1.91; n=5565), 3 (NLR≥1.92-2.52; n=5528), and 4 (NLR≥2.53; n=5617) differed significantly for all characteristics except gender (all P ≤.01). In general, use of antidepressants increased with NLR.

Depression and NLR used as a continuous variable were significantly related in the unadjusted model (odds ratio [OR], 1.13; 95% CI, 1.06-1.21; P <.001) and after adjusting for age, gender, ethnicity, education, marital status, and poverty income ratio (adjusted OR [aOR], 1.11; 95% CI, 1.04-1.20; P =.004). The relationship was attenuated after further adjusting for body mass index (BMI), physical activity, smoking status, and antidepressant use (aOR, 1.06; 95% CI, 0.98-1.15; P =.12). No significant relationships between depression and NLR quartiles were observed in the fully adjusted model.

In the fully adjusted model, NLR used as a continuous variable was significantly related with PHQ-9 scores (β, 0.08; 95% CI, 0.004-0.15; P =.04) as was quartile 1 (β, -0.18; 95% CI, -0.33 to -0.03; P =.02).

The relationship between NLR and depression severity was fit using a standard linear model (β, 0.08; 95% CI, 0.004-0.15; P =.04). The relationship was also fit using an infection point, in which the relationship was negative with an NLR of less than 1.78 (β, -0.21; 95% CI, -0.40 to -0.01; P =.04) and positive with an NLR of at least 1.78 (β, 0.39; 95% CI, 0.16-0.62; P =.001).

In a subgroup analysis, the relationship between NLR and depression severity was associated with moderate physical activity (β, 0.19; 95% CI, 0.04-0.34; P =.01). Black ethnicity (β, 0.19; 95% CI, 0.06-0.32; P =.004), Hispanic ethnicity (β, 0.16; 95% CI, 0.01-0.30; P =.04), BMI of 18.5 to 25 kg/m² (β, 0.15; 95% CI, 0.04-0.34; P =.045), and married or cohabitating status (β, 0.11; 95% CI, 0.03-0.20; P =.01).

The major limitation of this analysis is that the researchers obtained the NLR data at a single time point.

Study authors concluded, “The results suggest that the association between NLR and depression is not general across depression populations among US adults. This association may be specific to subgroups. The relationship between NLR and depression severity is non-linear. NLR is negatively related to depression severity when NLR is less than 1.78, and NLR is positively related to depression severity when NLR is above 1.78.”