Depressive and anxiety disorders have shown to be associated to premature or advanced biological aging and consequently to adversely impact somatic health. Treatments with antidepressant medication or running therapy are both found to be effective for many but not all patients with mood and anxiety disorders. These interventions may, however, work through different pathophysiological mechanisms and could differ in their impact on biological aging and somatic health. This study protocol describes the design of an unique intervention study that examines whether both treatments are similarly effective in reducing or reversing biological aging (primary outcome), psychiatric status, metabolic stress and neurobiological indicators (secondary outcomes).

Objective
The observed poorer physical function in persons with mental disorders could partly be due to dysregulation in physiological stress systems. However, an integrated picture of the role of physiological stress systems on objective physical function is lacking. This study examined the association of multiple physiological stress systems with objective physical function, and explored whether these stress systems contribute to the relationship between depression/anxiety and poorer physical function.
Methods
Data of 2860 persons of the Netherlands Study of Depression and Anxiety was used. Physical function was indicated by hand grip strength assessed using a hand-held dynamometer and lung function assessed using a peak flow meter. Inflammatory markers (CRP, IL-6, TNF-α), salivary cortisol (cortisol awakening response (AUCg, AUCi), evening cortisol) and ANS markers (heartrate, PEP, RSA) were determined. Depression/anxiety disorders were determined using psychiatric interviews. Linear regression analyses were adjusted for sociodemographics, health and lifestyle factors.
Results
Higher inflammation levels were associated with lower hand grip strength (BCRP = -0.21(SE = 0.06), p < .001) and lower lung function (BCRP = -2.07(SE = 0.66), p = .002), BTNF-α = −3.35(SE = 1.42), p = .022). Higher salivary cortisol levels were associated with lower lung function (Bevening cortisol = −2.22(SE = 0.59), p < .001). The association, in women, between depression/anxiety disorders and poorer physical function did not significantly diminish after adjustment for physiological stress markers.
Conclusion
This large cohort study showed that stress system dysfunction (especially the immune-inflammatory system and HPA-axis) contributes to poorer objective physical function. Stress system dysfunction did not explain the poorer physical function observed in persons with depression/anxiety disorders, suggesting that other pathways are involved to explain that association.

Background
Antidepressant medication and running therapy are both effective treatments for patients with depressive and anxiety disorders. However, they may work through different pathophysiological mechanisms and could differ in their impact on physical health. This study examined effects of antidepressants versus running therapy on both mental and physical health.
Methods
According to a partially randomized patient preference design, 141 patients with depression and/or anxiety disorder were randomized or offered preferred 16-week treatment: antidepressant medication (escitalopram or sertraline) or group-based running therapy ≥2 per week. Baseline (T0) and post-treatment assessment at week 16 (T16) included mental (diagnosis status and symptom severity) and physical health indicators (metabolic and immune indicators, heart rate (variability), weight, lung function, hand grip strength, fitness).
Results
Of the 141 participants (mean age 38.2 years; 58.2 % female), 45 participants received antidepressant medication and 96 underwent running therapy. Intention-to-treat analyses showed that remission rates at T16 were comparable (antidepressants: 44.8 %; running: 43.3 %; p = .881). However, the groups differed significantly on various changes in physical health: weight (d = 0.57; p = .001), waist circumference (d = 0.44; p = .011), systolic (d = 0.45; p = .011) and diastolic (d = 0.53; p = .002) blood pressure, heart rate (d = 0.36; p = .033) and heart rate variability (d = 0.48; p = .006).
Limitations
A minority of the participants was willing to be randomized; the running therapy was larger due to greater preference for this intervention.
Conclusions
While the interventions had comparable effects on mental health, running therapy outperformed antidepressants on physical health, due to both larger improvements in the running therapy group as well as larger deterioration in the antidepressant group.
Trial registration
Trialregister.nl Number of identification: NTR3460.