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Abstract
Background. Depression is clinically heterogeneous, and total Patient Health Questionnaire-9 (PHQ-9) scores can conceal symptom configurations with different inflammatory and metabolic correlates. Evidence linking immune-inflammatory activity and insulin resistance to depression has mostly addressed total symptom burden or binary thresholds.
Objective. To identify latent PHQ-9 symptom phenotypes in US adults and to evaluate whether the systemic immune-inflammation index (SII), the triglyceride-glucose index (TyG), and their interaction were associated with phenotype membership.
Methods. This cross-sectional secondary analysis used the National Health and Nutrition Examination Survey (NHANES) August 2021–August 2023 fasting subsample (adults aged at least 20 years with complete PHQ-9, blood count, fasting glucose, and triglyceride data). Survey-weighted ordinal latent class models (two to five classes) were compared. Multinomial regression (modal class membership; jackknife repeated-replication variance) adjusted for age, sex, race and ethnicity, education, body mass index, current smoking, and diabetes.
Results. Among 2,427 adults, a three-class solution was chosen: Minimal (53.4%), Somatic-dominant (32.5%), and Mixed-severe (14.1%); entropy was 0.810 and average posterior probability 0.915. In the adjusted sample (n = 2,409), odds ratios for Mixed-severe versus Minimal membership per one-standard-deviation increase were 1.16 (95% confidence interval [CI] 0.94–1.42) for SII, 1.10 (95% CI 0.89–1.36) for TyG, and 1.08 (95% CI 0.93–1.24) for SII×TyG. The global interaction test was not significant (p = 0.470). Continuous-score analyses agreed.
Conclusion. PHQ-9 responses identified three well-separated symptom phenotypes. SII, TyG, and their interaction did not independently distinguish phenotype membership. Phenotyping may refine epidemiological description. Single-occasion biomarkers of this kind should not currently assign depressive subtypes.
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