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How Vagus Nerve Robustness Is Linked to Depression Risk

Low vagal tone as indexed by heart rate and HRV may be a marker for depression.

Gordon Johnson/Pixabay
Source: Gordon Johnson/Pixabay

A few days ago, I wrote a post about how slower breathing facilitates eudaimonia via the vagus nerve. In that post, I presented a wide range of science-based evidence that identifies a correlation between more robust vagal tone as indexed by higher heart rate variability (HRV), lower blood pressure, increased flexibility of the autonomic nervous system, psychophysiological well-being, and overall happiness.

This morning, a press release, "Depression risk detected by measuring heart rate changes," from the 33rd annual European College of Neuropsychopharmacology (ECNP) Congress, grabbed my attention.

Because vagus nerve robustness plays a key role in lowering heart rate and increasing HRV, the moment I read the title of this release, I suspected it was probably a study related to the parasympathetic branch's autonomic nervous system functions, which are directly tied to vagal tone. Of note: HRV tends to be lower (Cavanaugh et al., 2019) in patients with major depressive disorder (MDD).

Sure enough, by using a 24-hour monitor to track people's heart rate (BPMs) and HRV, this new (2020) proof-of-concept study found that changes in autonomic nervous system functions as indexed by faster heart rates and lower HRV over a full circadian cycle were a reliable indicator of whether or not someone was experiencing depressive symptoms. Heart rate (HR) and HRV were measured using a portable mini-ECG attached to the skin.

"Put simply, our pilot study suggests that by just measuring your heart rate for 24 hours, we can tell with 90 percent accuracy if a person is currently depressed or not," lead researcher Carmen Schiweck of Goethe University, who presented the findings of this proof-of-concept study at the 33rd ECNP virtual congress (Sept. 12-15, 2020), said in the release. "We found that those with depression had both a higher baseline heart rate and a lower heart rate variation [HRV], as we expected," Schiweck added. "On average, we saw that depressed patients had a heart rate which was roughly 10 to 15 beats per minute higher than in controls."

"Normally, heart rates are higher during the day and lower during the night. Interestingly, it seems that the drop in heart rate during the night is impaired in depression. This seems to be a way of identifying patients who are at risk of developing depression or to relapse," Schiweck noted.

"This is an innovative proof-of-concept study," Brenda Penninx of the Department of Psychiatry at Amsterdam University Medical Centre (who was not involved in the study) commented in the release. "This study monitored heart rate variability in the ambulatory setting for several days and nights, which gives unique night and day information on the autonomic nervous system. It needs to be examined whether these interesting findings hold in larger, more diverse treatment settings."

A few years ago, a study (McLaughlin et al., 2015) by researchers from Harvard, McGill, UCLA, and the University of Washington found that low vagal tone magnifies the association between psychosocial stress exposure and mental health issues in adolescents. At the time, Katie McLaughlin and coauthors wrote:

"Although measures of autonomic nervous system function are frequently used as clinical markers of disease risk, they have not typically been employed as risk markers by mental health clinicians. In the current report, we examine the extent to which specific aspects of autonomic nervous system function might provide valuable information to clinicians about sensitivity to stress—the propensity to experience negative outcomes following exposure to stressors—and, potentially, risk for psychopathology in children and adolescents."

Based on their findings, McLaughlin et al. concluded: "It is possible that interventions that increase vagal tone would have positive influences on stress sensitivity and vulnerability to internalizing psychopathology among youths exposed to trauma or experiencing high degrees of social adversity."

In addition to improving vagal tone and autonomic nervous system flexibility by hacking the vagus nerve without using drugs (e.g., taking slower breaths and longer exhalations), the latest proof-of-concept study also tested a recently approved ketamine-based antidepressant treatment.

Whereas traditional antidepressants such as SSRIs typically take about 14 days to kick in, FDA-approved ketamine (from a certified doctor's office or clinic) is rapid-acting; ketamine's effects are often felt within a few hours. Another recent study (Selvaraj et al., 2018) found that "a single intravenous administration of ketamine (0.5 mg/kg) in patients with treatment-resistant depression (TRD) induces dramatic improvement in depression symptoms within four hours."

For their latest (2020) proof-of-concept study, Schiweck and colleagues at KU Leuven's Mind Body Research group in Belgium also gave a small sample of 16 patients with TRD and 16 healthy controls either ketamine or a placebo and monitored their HR/HRV for over 72 consecutive hours (4 days and 3 nights).

"After treatment, we again measured the heart rates and found that both the rate and [heart rate variability] of the previously depressed patients had changed to be closer to those found in the controls," Schiweck said.

Interestingly, the researchers also found that TRD patients with a higher resting heart rate at baseline responded more positively to ketamine treatments. These findings suggest that measuring heart rate and HRV for at least 24 consecutive hours may help identify which patients are more likely to respond well to ketamine before administering this antidepressant treatment.

"We need to remember that this is a small proof-of-concept study: 6 of our 16 initial patients responded to treatment with at least a 30 percent reduction on the Hamilton Rating Scale for depression," Schiweck concluded. "So, we need to repeat the work with a larger, antidepressant free sample. Our next step is to follow up depressed patients and patients who are in remission, to confirm that the changes we see can be used as an early warning system."


"Heart Rate and Heart Rate Variability as Trait or State Marker for Depression? Insights From a Ketamine Treatment Paradigm" presented by Carmen Schiweck at the 33rd ECNP Congress (September 12-15, 2020) via a virtual platform.

Grace Cavanaugh, Dede Greenstein, Cristan Farmer, Carlos Zarate, Jennifer Evans. "Heart Rate Variability in Patients With Treatment-Resistant Depression and Healthy Controls After Treatment With Ketamine." Biological Psychiatry (First published: May 15, 2019) DOI: 10.1016/j.biopsych.2019.03.878

Katie A. McLaughlin, Leslie Rith-Najarian, Melanie A. Dirks, and Margaret A. Sheridan. "Low Vagal Tone Magnifies the Association Between Psychosocial Stress Exposure and Internalizing Psychopathology in Adolescents." Journal of Clinical Child & Adolescent Psychology (First published online: October 24, 2013) DOI: 10.1080/15374416.2013.843464