Inflammatory Biomarkers in Chronic Pain Predict Psychiatric Morbidity: A Multi-Network EHR Cohort
A. S. Verma, V. Sharma, A. Pathak, R. GuptaIntroduction
There is an increased recognition of the role of systemic inflammation, mediated through inflammatory markers like IL-6, CRP, in pathophysiology of psychiatric disorders like depression, schizophrenia and substance abuse. While bidirectional influence of chronic pain and psychiatric morbidity is also understood, large-scale, real-world estimates on this topic remain limited. We aim to bridge this gap through a cohort study using TriNetX.
Objectives
To compare 5-year risk of major depressive disorder (MDD), suicidality, and substance use disorder (SUD) in chronic pain patients with high vs. low inflammatory biomarkers.
Methods
We used the TriNetX US Collaborative Network (71 health systems). Adults (≥18y) with chronic pain (ICD-10: G89.21, G89.28, G89.29, G89.4, M79.7) were stratified by inflammatory status using most-recent lab thresholds, each with ≥2 instances: high inflammation (ESR ≥20 mm/h [LOINC 4537-7], CRP ≥3 mg/L [1988-5], hs-CRP ≥3 mg/L [30522-7], or haptoglobin ≥200 mg/dL [4542-7]) vs. low (≤ these thresholds). Index was first date meeting pain + lab criteria; outcomes were assessed from day 1 to 5 years. Propensity-score matching (1:1) balanced demographics (642,785 per group post-match). We ran risk analyses excluding prior outcomes and Kaplan–Meier with log-rank tests and hazard ratios (Table 1)
Results
After matching, MDD risk over 5 years was 19.2% in the high-inflammation cohort vs. 17.9% in low-inflammation (risk ratio [RR] = 1.074, 95% CI 1.064–1.083; HR = 1.162, 95% CI 1.151–1.174; log-rank p<0.001). Suicidality risk was 2.1% vs. 1.8% (RR = 1.170, 95% CI 1.141–1.199; HR = 1.247, 95% CI 1.216–1.279; p<0.001). SUD risk was 11.5% vs. 10.3% (RR = 1.112, 95% CI 1.100–1.125; HR = 1.188, 95% CI 1.174–1.203; p<0.001) (Table 2). Absolute risk differences were +1.3% (MDD), +0.3% (suicidality), and +1.2% (SUD).
Image 1: Long description.