TOPLINE:

A post hoc analysis found that the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on cardiac and inflammatory stress responses was critically dependent on variability in baseline heart rate, with age acting as a moderator.

METHODOLOGY:

• Researchers conducted a single-blind crossover randomised controlled trial with 110 participants (51 control individuals and 59 patients with major depressive disorder [MDD]).
• Participants underwent both taVNS (at the right cymba concha) and sham stimulation (at the earlobe) on two separate days in a counterbalanced order.
• All participants were subjected to the modified Montreal Imaging Stress Task, and outcomes included cardiac reactivity measured using heart rate (HR) and root mean square of successive differences (RMSSD), emotional reactivity, and levels of inflammatory proteins (eg, TNF alpha and interleukin-6).
• The main analysis compared the effect of taVNS between the MDD and control groups. For the post hoc analysis, participants were stratified into low (n = 54) and high (n = 55) RMSSD groups using a median split at 39.14 milliseconds.

TAKEAWAY:

• The planned analysis found no differences in any outcomes between taVNS and sham stimulation when comparing participants with MDD and control individuals.
• In the low RMSSD group, taVNS improved cardiac vagal reactivity to stress and increased stress perception but had minimal effects on TNF alpha levels.
• In the high RMSSD group, the opposite pattern was observed: taVNS significantly decreased RMSSD (P < .001) and increased HR and TNF alpha levels (P = .038).
• Age was a moderator; effects of taVNS on RMSSD and HR variability were greater at age 20 years but lower at ages 40-60 years, but the interaction between intervention and RMSSD remained significant.

IN PRACTICE:

"Our findings indicate that baseline RMSSD matters, at least for the biological outcomes of taVNS. A compromised CPA [cardiac parasympathetic activity] (here approximated by RMSSD) is associated with impaired cardiac and inflammatory responses to acute stress exposure and can be improved by acute taVNS," the authors wrote, suggesting that consideration of both RMSSD and age is essential for future studies. 

"However, participants with high RMSSD may react with the opposite pattern, which could lead to null findings, as we observed in our analysis using diagnostic groups (eg, MDD vs controls)," they added.

SOURCE:

The study was led by Carmen Schiweck, University Hospital, Frankfurt, Germany. It was published online on December 06 in Translational Psychiatry.

LIMITATIONS:

The use of transcutaneous rather than invasive vagus nerve stimulation lacked the precision of direct vagal fibre stimulation. Respiration rates were not measured, which could have affected the reliability of RMSSD when respiration rates were outside the normal range. The analysis focused on secondary outcomes and may have lacked sufficient power to detect three-way interaction effects. Additionally, the observed effects on inflammation were small and limited to acute stimulation.

DISCLOSURES:

No funding information was reported. Several authors reported receiving intramural funding, speaker fees, travel funding, honoraria, or grants from charitable foundations; collaborative research hubs; the Federal Ministry of Education and Research, Germany; and pharmaceutical companies including Recordati, Otsuka Pharma GmbH, UCB, Janssen, Boehringer Ingelheim, and Cyclerion.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.