Differential associations of depression and anxiety with stress-related biomarkers.
Level 3 - non-randomized controlled study
Observational cohort study with cross-sectional and 10-year longitudinal analyses in two population-based samples
PubMed 42447674 · doi:10.1016/j.psyneuen.2026.107958
What was done
Data from two population-based cohorts, MIDUS 2 (n = 1190) and MIDUS Refresher (n = 806), were analyzed to assess whether stress biomarkers relate to general distress, depression-specific symptoms (anhedonia), or anxiety-specific symptoms (anxious arousal) via the Mood and Anxiety Symptom Questionnaire (MASQ). Measured biomarkers included diurnal cortisol slope, C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), and low-frequency heart rate variability (LF-HRV). Symptom relationships were compared against the Center for Epidemiologic Studies Depression Scale (CES-D), and exploratory 10-year longitudinal bidirectional associations were evaluated.
What was found
Across both cohorts, anxious arousal predicted flatter diurnal cortisol slope, higher CRP, higher IL-6, and lower LF-HRV, whereas anhedonia showed weaker and less consistent associations. Although CES-D depression scores replicated links to biomarker dysregulation, dimensional MASQ findings indicated these associations were largely driven by anxiety-related arousal. Exploratory 10-year longitudinal analyses showed bidirectional associations between anxious arousal and both flatter diurnal cortisol slope and lower LF-HRV. The abstract reports no exact numerical effect sizes, test statistics, or p-values.
Why it matters
Common depression questionnaires often conflate general distress and somatic anxiety, which may lead to incorrect assumptions about the biological markers of pure depressive symptoms. Disentangling symptom clusters shows that physiological stress dysregulation is primarily driven by anxious arousal rather than anhedonia.
Limits
No exact effect sizes, confidence intervals, or numerical data are reported in the abstract. The study relies on self-report symptom scales rather than structured clinical diagnostic interviews. The 10-year longitudinal analyses were exploratory, and observational cohort designs cannot rule out residual confounding from unmeasured lifestyle or medical variables.
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