# No relationship between inflammatory cytokines, heart rate variability, and morphology of the vagus nerves in patients with major depressive disorder

## TL;DR

This study found no link between inflammation markers, vagus nerve structure, and heart rate variability in people with major depression.

## Contribution

It is the first to investigate the relationship between inflammatory cytokines, vagus nerve morphology, and HRV in MDD patients.

## Key findings

- MDD patients had higher IL-1 beta and TNF-alpha levels compared to controls.
- No correlation was found between inflammatory cytokines, HRV, and vagus nerve morphology after adjusting for BMI.
- BMI was significantly correlated with hsCRP and HRV parameters in all participants.

## Abstract

Patients with major depressive disorder (MDD) often show of a low-grade inflammation. Inflammatory cytokines are assumed to be transmitted from the periphery to the brain, amongst others, via the vagus nerves (VN), which constitute a pivotal part of the microbiota-gut-brain axis. While functional aspects of the VNs (heart rate variability (HRV)) were extensively studied in patients with MDD, less is known about morphological alterations. Aim of this study was to examine the relationship between inflammatory cytokines, morphology, and function of the VNs in patients with MDD and healthy controls. Markers of inflammation (tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), and high-sensitive C-reactive protein (hsCRP)) were measured in 50 patients with MDD and 50 age- and sex-matched healthy controls. Inflammatory cytokines were correlated with sonographic characteristics of the VN (cross-sectional area and echogenicity) and with HRV at rest, during standing, and under slow paced breathing. Patients with MDD had significantly higher serum levels of IL-1 beta (0.17 ± 0.13 versus 0.09 ± 1.22 pg/ml, p < 0.001) and of TNF-alpha (0.72 ± 0.23 versus 0.62 ± 0.22 pg/ml, p = 0.013), while levels of hsCRP (1.91 ± 3.02 versus 1.60 ± 2.24 mg/l) were similar between groups. There was a significant correlation between body mass index (BMI) and hsCRP, as well as HRV parameters at rest in all participants. Controlling for the BMI, we found no correlation between inflammatory cytokines, HRV, and morphology of the VNs in patients with MDD. Therefore, further studies are warranted to address the assumed relationship between inflammation, morphology, and function of the VNs in patients with MDD.