Circulating inflammatory markers, cell-free mitochondrial DNA, cortisol, endocannabinoids, and N-acylethanolamines in female depressed outpatients

Abstract

Objectives

Major depressive disorder (MDD) involves peripheral low-grade pro-inflammatory activity. This multi-biomarker case-control study characterises the proinflammatory status in MDD beyond C-reactive protein (CRP) and Interleukin (IL)-6 levels through investigating concomitant alterations of immunoregulatory biomolecules.

Methods

In 20 female MDD patients and 24 non-depressed women, circulating levels of CRP, IL-6, cortisol, selected endocannabinoids (ECs; anandamide [AEA], 2-arachidonylglycerol [2-AG]), and N-acylethanolamines (NAEs), as well as circulating cell-free mitochondrial DNA (ccf-mtDNA) were measured.

Results

We found higher serum CRP and plasma AEA levels in MDD and a positive association of CRP and AEA levels with current depressive symptoms. Blood levels of cortisol, ccf-mtDNA, 2-AG, and NAEs did depend on MDD diagnosis nor correlated with the severity of current depressive symptoms. CRP correlated positively with AEA, and AEA showed positive associations with 2-AG and NAE levels.

Conclusions

In this study, female MDD outpatients with mild to moderate disorder severity did not substantially differ from non-depressed controls in the resting levels of multiple immunoregulatory markers in peripheral blood. Instead of investigating resting levels, future research on the role of inflammatory activity in MDD should focus on investigating the reactivity of pathways modulating the immune system upon exposure to physical and psychosocial stressors.

Keywords:

• Depression
• inflammation
• morning cortisol
• mitochondrial DNA
• endocannabinoids

Acknowledgements

None.

Disclosure statement

The authors report no conflict of interest.

Data availability statement

Participants of this study did not agree for their data to be shared publicly, so supporting data is not available.

Additional information

Funding

This work was supported by prize money from the ‘Ulm University contest of ideas’ (Ulm University, Germany), which was used to conduct data collection, sample generation, and biological analyses.