ABS 036: Why Normal Isn't Normal: PHQ-8 Depression Screening Inadvertently Detects Multi-System Dysfunction Hidden Within Standard Laboratory Ranges (NHANES 2013-2023)

Kirsten Kilponen ¹

¹ Hunter College

The Van Wickle Journal (2026) Volume 2, ABS036

Introduction: Fatigue, sleep disturbance, appetite changes, and difficulty concentrating (hallmark PHQ-8 symptoms) are often indistinguishable from autoimmune, metabolic, and inflammatory disorder symptoms. Patients with elevated PHQ-8 scores routinely present with "unremarkable" laboratory results, leading to psychiatric diagnosis and SSRI prescription. Treatment-resistant depression affects 2.8 million Americans, costing $25.8 billion annually, raising a fundamental question: what if the PHQ-8 inadvertently screens for physiological illness rather than psychiatric pathology?

Prior research examined isolated biomarkers in small clinical samples. No study has assessed coordinated multi-system patterns. We analyzed NHANES data (2013-2023, ages 25-74), examining 80-105 biomarkers per cycle across six physiological systems. While we anticipated correlations, patterns substantially exceeded expectations.

Methods: Participants were stratified into PHQ-8 bins (0-4, 5-9, 10-14, ≥15) across four NHANES cycles (2013-2023). Dual approaches employed arithmetic means (combined sexes) then geometric means (sex-stratified) to account for log-normal distributions. Percentage deviations from baseline and monotonicity were assessed via Spearman (ρ) and Kendall (τ), with strict monotonicity defined as unidirectional progression across bins.

Results: Across ten years, 90-97% of biomarkers demonstrated monotonic or near-monotonic relationships with PHQ-8 severity, with peaks at PHQ 10-14 or ≥15. At PHQ≥15 relative to baseline: hs-CRP increased 76%, urine albumin 162%, albumin-creatinine ratio 92%, triglycerides 26-30%, and insulin 51% (females). Micronutrient patterns indicated metabolic dysfunction: vitamin D3 declined while D2 remained stable, omega-3s decreased while arachidonic acid remained unchanged, and active folate fell as unmetabolized folic acid accumulated. Hematologic markers remained stable (hemoglobin -1-2%) despite metabolic dysregulation. Sex dimorphism reversed conventional patterns: males showed larger inflammatory effects (hs-CRP +60% versus +31% females).

Discussion: These findings indicate PHQ-8 functions as a screener for physiological dysfunction rather than psychiatric pathology. This suggests reexamining "normal" laboratory cutoffs, alternative referral pathways before SSRI prescription, precision medicine approaches, and mechanistic research over micronutrient supplementation. Clinical implementation is critical: screening instruments shape diagnostic trajectories, diagnostic labels shape treatment pathways, and treatment pathways shape patients' lives.