Basal and LPS-stimulated inflammatory markers and the course of anxiety symptoms.
Level 3 - non-randomized controlled study
Prospective longitudinal cohort study with repeated measures over 9 years
PubMed 34509625 · doi:10.1016/j.bbi.2021.09.001
What was done
Researchers evaluated the longitudinal relationship between baseline basal and lipopolysaccharide (LPS)-stimulated inflammatory markers and anxiety symptom severity across five assessment waves over nine years. The study included up to 2,867 participants from the Netherlands Study of Depression and Anxiety (NESDA), of whom 43.6% had a current anxiety disorder at baseline (social phobia was most prevalent at 18.5%). Anxiety symptoms were assessed using the Beck Anxiety Inventory (BAI), Fear Questionnaire (FQ), and Penn State Worry Questionnaire (PSWQ). Multivariate-adjusted mixed models were used to analyze the associations over time, with additional adjustment for comorbid major depressive disorder.
What was found
Baseline inflammatory markers were significantly associated with anxiety symptom severity over the nine-year follow-up. The strongest effects were observed for somatic arousal symptoms (BAI somatic subscale) and agoraphobia (FQ subscale), with standardized beta-coefficients up to 0.14. Adjusting for comorbid major depressive disorder attenuated these associations by 25% to 30%, but they remained statistically significant.
Why it matters
This study provides prospective evidence that low-grade basal and stimulated inflammation relates specifically to persistent physical arousal and agoraphobic anxiety symptoms over nearly a decade. It also demonstrates that this inflammatory link is partially shared with depressive comorbidity rather than being entirely specific to anxiety.
Limits
Effect sizes were small (standardized betas up to 0.14), limiting individual clinical predictive value. The abstract does not report specific levels or distinct findings for individual cytokines versus CRP or basal versus LPS-stimulated conditions. As an observational study, residual confounding cannot be excluded, and causality cannot be established.
Cited by
- contradicts In the 9-year Netherlands Study on Anxiety and Depression, serum LPS was the only biomarker associated with 100% of anxiety and depression cases and predicted symptom severity.