Differential associations of depression and anxiety with stress-related biomarkers

A large body of research links depression and anxiety with markers of chronic stress, including cortisol dysregulation and systemic inflammation. However, it is unclear whether these associations reflect disorder-specific features or shared general distress, as diagnostic criteria and overlapping measures often conflate symptoms of both conditions.

Using data from the MIDUS 2 and MIDUS Refresher studies (N = 1190; 806), we examined diurnal cortisol slope (DCS), C-reactive protein (CRP), interleukins (IL-6 and IL-10), tumor necrosis factor-α (TNF-α), and low-frequency heart rate variability (LF-HRV) in relation to Mood and Anxiety Symptom Questionnaire (MASQ) symptom dimensions: general distress (common to depression and anxiety), anhedonia (specific to depression), and anxious arousal (specific to anxiety).

Across two large, population-based samples, anxious arousal predicted flatter DCS, higher CRP and IL-6, and lower LF-HRV, whereas anhedonia showed weaker and less consistent associations. Exploratory analyses using the Center for Epidemiologic Studies Depression Scale (CES-D), a widely used depression measure that also captures general distress and anxiety, replicated findings linking depression to biomarker dysregulation. However, the MASQ findings suggest that such associations may largely reflect anxiety-related arousal symptoms. Exploratory 10-year longitudinal analyses revealed bidirectional associations between anxious arousal and both flatter DCS and lower LF-HRV.

Findings suggest that there is overlooked nuance in research linking depression with cortisol, inflammation, and HRV. Depression measures might be confounded with anxiety symptoms, and the anxious arousal symptom cluster might be particularly strongly related to specific markers of chronic stress.