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Stress and Heart Rate Variability: A Meta-Analysis and Review of the


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Article in Psychiatry Investigation · February 2018


DOI: 10.30773/pi.2017.08.17

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REVIEW ARTICLE Print ISSN 1738-3684 / On-line ISSN 1976-3026
https://doi.org/10.30773/pi.2017.08.17 OPEN ACCESS

Stress and Heart Rate Variability: A Meta-Analysis and


Review of the Literature
Hye-Geum Kim1, Eun-Jin Cheon2, Dai-Seg Bai3, Young Hwan Lee2* , and Bon-Hoon Koo1* 
1
Department of Psychiatry, College of Medicine, Yeungnam University, Daegu, Republic of Korea
2
Department of Pediatrics, College of Medicine, Yeungnam University, Daegu, Republic of Korea
3
Division of Clinical Psychology, Department of Psychiatry, Yeungnam University Medical Center, Daegu, Republic of Korea

Objective Physical or mental imbalance caused by harmful stimuli can induce stress to maintain homeostasis. During chronic stress,
the sympathetic nervous system is hyperactivated, causing physical, psychological, and behavioral abnormalities. At present, there is no
accepted standard for stress evaluation. This review aimed to survey studies providing a rationale for selecting heart rate variability
(HRV) as a psychological stress indicator.
Methods Term searches in the Web of Science®, National Library of Medicine (PubMed), and Google Scholar databases yielded 37
publications meeting our criteria. The inclusion criteria were involvement of human participants, HRV as an objective psychological stress
measure, and measured HRV reactivity.
Results In most studies, HRV variables changed in response to stress induced by various methods. The most frequently reported factor
associated with variation in HRV variables was low parasympathetic activity, which is characterized by a decrease in the high-frequency
band and an increase in the low-frequency band. Neuroimaging studies suggested that HRV may be linked to cortical regions (e.g., the
ventromedial prefrontal cortex) that are involved in stressful situation appraisal.
Conclusion In conclusion, the current neurobiological evidence suggests that HRV is impacted by stress and supports its use for the ob-
jective assessment of psychological health and stress. Psychiatry Investig 2018;15(3):235-245

Key Words H
 eart rate variability, Stress, Autonomic nervous system.

INTRODUCTION or chronic physical, psychological, and behavioral impairment.2


The search for stress biomarkers remains a challenging task
Hans Selye defined stress as “a response to change in order for researchers and clinicians as there are several obstacles. One
to maintain the state of stability or homology that the body obstacle is a lack of consensus on the definition of stress. More-
has maintained against the stimulus to break the mental and over, we lack a comprehensive framework for investigating
physical balance and stability of the body.”1 Stress was also how organisms function in and adapt to constantly changing
defined by Kenneth Hambly as a maladaptive state in which environments.3 At present, there is no universally recognized
the sympathetic nervous system is overactivated, causing acute standard for stress evaluation. A number of studies using exist-
ing stress measurement methods (e.g., psychological measures
Received: May 5, 2017 Revised: August 1, 2017 of stress) and examining biological markers (e.g., cortisol, am-
Accepted: August 17, 2017 ylase) have been performed. Moreover, studies on heart rate
 Correspondence: Bon-Hoon Koo, MD, PhD
Department of Psychiatry, College of Medicine, Yeungnam University, 170 Hy-
variability (HRV) and stress are increasing in frequency. HRV
eonchung-ro, Nam-gu, Daegu 42415, Republic of Korea is the fluctuation of the length of heart beat intervals.4 HRV
Tel: +82-53-620-3343, Fax: +82-53-629-0256, E-mail: [email protected]
represents the ability of the heart to respond to a variety of
 Correspondence: Young Hwan Lee, MD, PhD
Department of Pediatrics, College of Medicine, Yeungnam University, 170 Hy- physiological and environmental stimuli.5 Low HRV conveys
eonchung-ro, Nam-gu, Daegu 42415, Republic of Korea a monotonously regular heart rate. Moreover, low HRV is as-
Tel: +82-53-640-6999, Fax: +82-53-629-2252, E-mail: [email protected]
*These authors contributed equally to this work.
sociated with impaired regulatory and homeostatic autonom-
cc This is an Open Access article distributed under the terms of the Creative Commons ic nervous system (ANS) functions, which reduce the body’s
Attribution Non-Commercial License (http://creativecommons.org/licenses/by- ability to cope with internal and external stressors. Thus,
nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduc-
tion in any medium, provided the original work is properly cited. HRV is a noninvasive electrocardiographic method that can

Copyright © 2018 Korean Neuropsychiatric Association 235


Stress and Heart Rate Variability

be used to measure the ANS in a variety of clinical situations tonomic Nervous System’ OR ‘Cardio-Vascular Reactivity’)]”;
(e.g., during psychological stress evaluations).6 Many research- 2) PubMed, “stress (Title) AND [‘HRV’ (Title/Abstract) OR
ers have conducted studies that used HRV to measure stress, ‘Heart Rate Variability’ (Title/Abstract)]”; and 3) Google Schol-
operating under the assumption that HRV is a reliable index ar, “allintitle: stress AND (‘Heart Rate Variability’ OR ‘HRV’).”
of stress. However, few studies have confirmed whether HRV The inclusion criteria were that each study involving human
is a good indicator of stress. In this review, we examined the participants, used HRV as an objective measure of psycholog-
literature providing a rationale for selecting HRV as a reliable ical stress, and measured HRV reactivity by evaluating any HRV
indicator of psychological stress. The value of HRV as a stress variables calculated using frequency-based or time-based mea-
indicator must be assessed to support its future clinical use as sures. Secondary references and other literature providing the-
a noninvasive and simple diagnostic test. oretical evidence for selecting HRV as a stress indicator or the
role of the ANS in psychological stress and heart rate were also
Methods included in the study. Each of the database searches yielded
107 studies matching the inclusion criteria. Subsequently, we
The Web of Science® (WoS), National Library of Medicine excluded studies that did not concur with the purpose of the
(PubMed), and Google Scholar databases were searched for literature review (e.g., studies assuming HRV is an objective
articles published from 2007 to 2017 pertaining to psychoso- measure of psychological stress and using it as a dependent
cial stress and HRV. The following combination of terms was variable). Ultimately, 37 studies meeting our criteria were se-
used for each database search: 1) WOS, “[Title (TI)=(stress) lected for this review (Figure 1).
AND TI=(‘Heart rate’ OR ‘Heart Rate Variability’ OR ‘HRV’
OR ‘Cardiac Vagal Control’ OR ‘Cardiac Vagal Tone’ OR ‘Au-
Identification

Web of Science Pubmed Google scholar


(N=273) (N=327) (N=302)

Records after duplicates removed


(N=235)
Screening

Records excluded (N=183)


Not studies on human
Records screened Not studies on healthy human
(N=235) No HRV measured
No measured HRV reactivity by
any HRV variables
Review papers
Eligibility

Full-text articles excluded (N=15)


Full-text articles assessed
Studies assuming HRV is an objective
for eligibility
measure of psychological stress and
(N=52)
using it as a dependent variable
Included

Studies included
in meta-analysis
(N=37)

Figure 1. Flow chart of study selection in the meta-analysis. HRV: heart rate variability.

236 Psychiatry Investig 2018;15(3):235-245


HG Kim et al.

Results static stress showed minimal individual variation. In con-


trast, psychological stressors produced widespread individual
Autonomic regulation of psychological stress differences in the autonomic response. In response to psy-
conditions chological stressors, participants either showed sympathetic
The two main pathways by which psychological stress af- activation, vagal withdrawal, or a reciprocal pattern of auto-
fects the body are the hypothalamic-pituitary-adrenal (HPA) nomic response.13 These findings show that individuals differ
axis and sympathetic nervous system (SNS).7 The ANS and in how they respond to psychological stressors.
HPA axis are highly coordinated and interconnected.8 The ANS
quickly promotes physiological changes through the SNS Autonomic cardiac control
and parasympathetic nervous system (PNS). The PNS pro- Although cardiac automaticity is intrinsic to various pace-
motes the sympathetic response to stress, commonly referred maker tissues, heart rate (HR) and rhythm are largely under
to as a fight or flight response, by withdrawing the inhibitory the control of the ANS.15 HR is controlled by the balancing ac-
effect.9 A series of changes follows, including the release of tion of the SNS and PNS branches. The parasympathetic in-
noradrenaline from the locus coeruleus.10 During the stress fluence on HR is mediated by the release of acetylcholine from
response, the HPA axis triggers a series of endocrine chang- the vagus nerve. Muscarinic acetylcholine receptors respond
es, beginning with the release of corticotropin releasing hor- to this release by increasing cell membrane K+ conductance.16,17
mone from the hypothalamus.8,11 Specifically, the PNS plays The sympathetic influence on HR is mediated by the release
an important role in alleviating the stress response of individ- of epinephrine and norepinephrine. β-adrenergic receptors
uals by inhibiting or inhibiting the SNS and HPA axis.8 Stress are activated by the release of these hormones, which results
is associated with variations in autonomic activity that dis- in cAMP-mediated phosphorylation of membrane proteins.18
rupt homeostatic processes.9 The ANS responds to the needs Increased SNS or diminished PNS activity results in cardio-
of the internal viscera as well as external stimuli. Homeosta- acceleration, whereas decreased SNS or increased PNS activ-
sis is associated with the regulation of internal viscera, where- ity causes cardio-deceleration.5 The SNS mainly acts on the
as the stress response prioritizes external stimuli over internal ventricular muscles and increases their contractility. More-
needs. Thus, stress occurs when an organism’s physiological over, the SNS increases the excitation frequency, excitation
demands are no longer adequately fulfilled by the PNS. Con- conduction velocity, and excitability of the sinoatrial (SA)
sequently, the measurement of parasympathetic tone may node. When the SNS is maximally stimulated, the magnitude
serve as an index of stress and stress vulnerability. Moreover, of the HR and contractility can triple and double, respective-
stasis, which is a lack of endogenous variability in neurally me- ly. The PNS primarily acts on the SA and atrioventricular (AV)
diated peripheral systems (e.g., heart rate), is a sign of severe nodes to reduce HR. Vagal and sympathetic activity constant-
physiological distress.9 ly interacts. As the SA node is rich in acetylcholinesterase, the
The homeostatic functions of the ANS are demonstrated by effect of the vagal impulse is brief, owing to rapid hydrolysis
the baroreceptor-heart rate reflex, a reciprocal change in the of acetylcholine.19,20 Under resting conditions, vagal tone pre-
activities of the ANS.12 Baroreceptor reflexes are organized vails over sympathetic activity, and variations in the heart
largely within lower central autonomic substrates at the brain- period are largely dependent on vagal modulation. When the
stem level. However, through the evolutionary development SNS and PNS are removed, the HR rises above steady-state
of the rostral brain systems, these lower autonomic systems rates. Vagal dominance occurs when the vagus nerve, which
became integrated with higher neural networks.13 The limbic is a parasympathetic nerve in the stable state, is more active
system and forebrain including the hypothalamus, amygdala, than sympathetic nerves. Dysregulation of the autonomic ner-
and medial prefrontal cortex, have been shown to issue syn- vous control of the cardiovascular system is associated with
aptic projections to brainstem reflex networks as well as to au- increased sympathetic and reduced parasympathetic tone
tonomic regions.12 Stressors can lead to an inhibition or shift and plays an important role in coronary artery disease and
in the set point of baroreceptor reflexes.12,14 Brainstem barore- the genesis of potentially lethal ventricular arrhythmias.6,21
ceptor reflexes exert reciprocal control over the two autonom- Separate rhythmic contributions from sympathetic and para-
ic branches (i.e., SNS and PNS).12 sympathetic autonomic activity modulate the HR intervals of
The reciprocal mode of autonomic control can vary under the QRS complex in the electrocardiogram (ECG) at distinct
different circumstances. Using selective pharmacological block- frequencies. In this context, the degree of variability in the HR
ades targeting the SNS and PNS, Berntson et al.13 found that provides information about the functioning of nervous con-
orthostatic challenges and standard psychological stressors trol on the HR and the heart’s ability to respond. Since the
produced distinct patterns of control. Responses to ortho- heart is not a metronome and its beats are irregular, HRV is

www.psychiatryinvestigation.org 237
Stress and Heart Rate Variability

normal and to be expected. Moreover, HRV indicates the search and psychophysiology. After that, HRV was treated as
heart’s ability to respond to multiple physiological and envi- a descriptive variable without being attributed to any specific
ronmental events, (e.g., breathing, physical exercise, mental physiological state. At present, understanding of HRV inter-
stress, hemodynamic and metabolic changes, and sleep and pretation is increasing, and we are also aware of the interac-
orthostatism) and compensate for disease-induced disor- tion between HRV’s underlying physiological mechanisms
ders.5,22-25 HRV can be used as a valuable tool to measure the and behavioral processes.29
sympathetic and parasympathetic function of the ANS.5 HRV variables are summarized in Tables 1 and 2.15 In 1996,
the Task Force of the European Society of Cardiology (ESC)
Theoretical significance of heart rate variability and the North American Society of Pacing and Electrophysi-
Long before the modern technology of HRV was invented, ology (NASPE) defined and established standards for the mea-
physicians recognized the potential importance of heart rhythms. surement, physiological interpretation, and clinical use of
In 1847, Ludwig was able to observe a quickening of pulse rate HRV. Time-domain and frequency-domain indices and geo-
with inhalation and a slowing with exhalation in the dog.26 metric measures are standard clinical parameters.15 Time-do-
This was the first report of respiratory sinus arrhythmia (RSA). main analysis measures variation in HR over time or the inter-
Moreover, in 1868, Donders examined the relationship be- vals between successive normal cardiac cycles. Time-domain
tween respiration, HR, and the vagus nerve.27 In 1920, Bain- analysis of recording data involves simple calculations of mean
bridge explained RSA in terms of alterations in baroreceptor normal-to-normal (NN) intervals and the variance between
and volume receptor responses associated with respiratory al- NN intervals. One of the simplest time-domain analysis vari-
terations in thoracic pressure.28 Moreover, in 1915, the studies ables is the standard deviation of the NN interval (SDNN; i.e.,
of Eppinger and Hess focused on clinical issues related to pu- the standard deviation of NN). When HRV is large and irreg-
tative abnormalities in autonomic functions. They focused on ular, the SDNN value increases. Therefore, SDNN is an index of
the potential role of the ANS in atypical physiological respons- physiological resilience against stress. In contrast to SDNN,
es and clinical disorders. Their studies also emphasized the which is computed directly from the NN interval, the root
activity of the vagus nerve, which may allow pharmacologi- mean square of the successive differences (RMSSD), number
cal manipulations and potential treatments.29 In 1967, Wolf of interval differences of successive NN intervals greater than
viewed HRV as reflecting brain-vagal-heart communication.30 50 ms (NN50), and proportion derived by dividing NN50 by
Wolf provided an important connection between clinical re- the total number of NN intervals (pNN50) are derived from
Table 1. Heart rate variability (HRV) time-domain measures15
Variable Units Description
Statistical measures
SDNN ms Standard deviation of all NN intervals
SDANN ms Standard deviation of the averages of NN intervals in all 5-minute segments of the entire recording
RMSSD ms The square root of the mean of the sum of the squares of differences between adjacent NN intervals
SDNN index ms Mean of the standard deviations of all NN intervals for all 5-minute segments of the entire recording
SDSD ms Standard deviation of differences between adjacent NN intervals
NN50 count Number of pairs of adjacent NN intervals differing by more than 50 ms in the entire recording; three
variants are possible counting all such NN intervals pairs or only pairs in which the first or the second
interval is longer
pNN50 % NN50 count divided by the total number of all NN intervals
Geometric measures
HRV triangular Total number of all NN intervals divided by the height of the histogram of all NN intervals measured on
index a discrete scale with bins of 7.8125 ms (1/128 seconds)
TINN ms Baseline width of the minimum square difference triangular interpolation of the highest peak of the
histogram of all NN intervals
Differential index ms Difference between the widths of the histogram of differences between adjacent NN intervals measured
at selected heights (e.g., at the levels of 1,000 and 10,000 samples)
Logarithmic index Coefficient φ of the negative exponential curve k · e−φt, which is the best approximation of the histogram
of absolute differences between adjacent NN intervals
NN: normal-to-normal

238 Psychiatry Investig 2018;15(3):235-245


HG Kim et al.

Table 2. Heart rate variability (HRV) frequency-domain measures15


Variable Units Description Frequency range
Analysis of short-term recordings (5 min)
5-min total power ms2 The variance of NN intervals over the temporal segment ≈≤0.4 Hz
VLF ms 2
Power in VLF range ≤0.04 Hz
LF ms2 Power in LF range 0.04–0.15 Hz
LF norm nu LF power in normalized units LF/(total power-VLF)×100
HF ms 2
Power in HF range 0.15–0.4 Hz
HF norm nu HF power in normalized units HF/(total power-VLF)×100
LF/HF Ratio LF (ms2)/HF (ms2)
Analysis of entire 24 hours
Total power Variance of all NN intervals ≈≤0.4 Hz
ULF Power in the ULF range ≤0.003 Hz
LF Power in the VLF range 0.003–0.04 Hz
VLE Power in the LF range 0.04–0.15 Hz
HF Power in the HF range 0.15–0.4 Hz
α Slope of the linear interpolation of the spectrum in a log-log scale ≈≤0.04 Hz
VLF: very low frequency band, LF: low-frequency band, HF: high-frequency band, ULF: ultra low frequency band

the difference between adjacent NN intervals. These variables tionship between the number of job stressors, self-reported
are impacted by the PNS, as they reflect beat-to-beat chang- sleep quality, and daytime autonomic activities. They found
es.31,32 Power Spectral Density (PSD) analysis of the frequen- no correlation between the HRV parameters and five job stress-
cy domain provides information about how power is distrib- or scores.36 However, subsequent studies have reported that
uted (i.e., the variance) as a function of frequency, which allows some HRV indicators reflect psychological stress. Studies of
autonomic balance to be quantified at any given time. By using healthy human individuals that examined HRV variation as-
PSD analysis to understand HRV, we can distinguish between sociated with psychologically stressful situations are summa-
the activity of the SNS and PNS. Frequency-domain analysis is rized in Table 3. There was heterogeneity among the studies
preferred for short-term measurements (i.e., 5 min). PSD anal- concerning the type of stress-eliciting task used and HRV re-
ysis allows the intensity of the HRV spectral components [i.e., activity (i.e., laboratory environment task or subjective stress
the high-frequency band (HF), low-frequency band (LF), and reports). Moreover, the HRV reactivity studies were either
very low frequency band (VLF)] to be determined. Different short-term (5 min) or continuous 24-h studies. In most stud-
HRV spectral components are associated with either the sym- ies, HRV variables changed in response to stress induced by
pathetic or parasympathetic branches of the ANS. The HF is a various methods. However, the presence of significant varia-
measure of PNS activity, as it reflects the activity of the vagus tion in HRV variables was inconsistent. The most frequently
nerve, whereas LF reflects the activity of the SNS.33,34 reported factor associated with variation in HRV variables
was low parasympathetic activity, which is characterized by a
Studies of HRV reactivity to psychological stressors decrease in the HF and an increase in the LF. Dimitriev et al.37
in healthy human participants recently reported that mental stress leads to an increase in
Sloan et al.35 analyzed 24-h electrocardiographic record- predictability, RR interval regularity, and reduced complexity.
ings from 33 healthy participants to examine the association This reflects a change toward more stable and periodic HR
between the RR interval, HRV responses, and periodic diary behavior under stress. Reduced HRV and inhibited parasym-
entries measuring physical position, negative affect, and time pathetic activation increase vulnerability to future stress.
of day. As expected, their results showed that increases in stress
were associated with decreases in the RR interval. Moreover, Neurobiological evidence of HRV as a stress
psychological stress was significantly associated with an in- measurement
crease in the LF/HF ratio, suggesting increased SNS activity Many of the studies examined were consistent with Claude
during stressful periods of the day.35 Using a questionnaire Bernarde’s (1865) finding that the vagus nerve serves as a
survey and short-term HRV recordings of 223 healthy male structural and functional link between the brain and the heart.
white-collar workers, Kageyama et al.36 investigated the rela- His work was among the earliest to systematically investigate

www.psychiatryinvestigation.org 239
Table 3. Studies of HRV reactivity to psychological stressors in healthy human participants

240
Age Significantly changed
Authors Year N Stress evaluation HRV measures Major findings
(mean±SD, range) HRV measures
Kageyama et al.36 1998 223 30.8±5.4 (21–42) Questionnaire survey Short-term None of the HRV parameters were None
(perceived job stressors) HF, LF, LF/HF correlated to any of five job stressor
scores.
Kaegi et al.57 1999 17 Medical residents Scenario simulating a 24 hr continious HR significantly increased during mental HR, LF, HF, LF/HF
medical emergency HR, LF, HF, LF/HF stress.
Stress and Heart Rate Variability

Delaney et al.58 2000 30 (14M, 16F) 34.4±8.7 (18–56) Stroop Word Color Short-term Simple, cost-effective method of analysing HR, pNN50, TP, LF,
in male Conflict Test (to produce HR, pNN50, TP, VLF, LF, HRV is suitable for detection of short- HF, LFnu, HFnu,
30.9±3.9 (25–36) psychological strain) HF, LFnu, HFnu, LF/ term changes in sympathovagal balance. LF/HF
in female HF

Psychiatry Investig 2018;15(3):235-245


Vrijkotte et al.59 2000 109 47.2± 5.3 (35–55) Monitored HRV on 2 24 hr continious The detrimental effects of work stress are HR, RMSSD
workdays and 1 non- HR, RMSSD partly mediated by increased HRV to a
workday stressful workday, and lower vagal tone.
Dishman et al.60 2000 92 (52M 40F) Self-ratings of trait anxiety Short-term This indicates a lower cardiac vagal HF
and perceived emotional LF, HF component of HRV among men and
stress women who perceived more stress.
Lucini et al.61 2002 30 22±1 30 to 60 minutes before an Short-term Mild real-life stress increases arterial RR, LF, HF, HFnu,
university examination RR, RR variance, LFnu, pressure and impairs cardiovascular LF/HF,
HFnu, LF/HF homeostasis.
Hjortskov et al.62 2004 12 female 23.7±4.8 Computer-work-related Short-term Reduction in the HF and an increase in HF, LF/HF
mental stressors (either LF, HF, LF/HF the LF/HF were observed in the stress
added to or removed situation compared to the control session.
from a standardized
computer work session
in the laboratory)
Kang et al.63 2004 169 male Aged over 40 Job Contect Short-term SDNN was significantly lower in the high SDNN
Questionnaire SDNN, RMSSD, LF, HF, strain group than in the low strain
VLF, LF/HF group. However, they could not find a
significant association in LF/HF ratio.
Hintsanen et al.64 2007 406M, 457F Mean age 32.3 Effort-reward imbalance Short-term Higher effort-reward imbalance was HR, RMSSD, pNN50
(ERI) questionnaire HR, RMSSD, pNN, HF, associated with lower HRV, and lower
LF/HF reward was associated with higher HR
among women, not men.
Table 3. Studies of HRV reactivity to psychological stressors in healthy human participants (continued)
Age Significantly changed
Authors Year N Stress evaluation HRV measures Major findings
(mean±SD, range) HRV measures
Orsila et al.65 2008 30 (15M, 15F) 40±8.8 (24–62) Perceived mental stress Wristop continious Highest correlation between perceived TINN, RMSSD, SD1
during the workday MeanHR, MeanRR, mental stress with the differences
RMSSD, TINN, LF, H between the values of TINN and the
F, LF/HF, SD1, SD2 RMSSD obtained in the morning and
during the workday.
Chandola et al.66 2008 10,308 Range 35–55 Job-strain questionnaire Short-term There was an association between work LF. HF, SDNN
(3413M, 6895F) (Self-reported work RR, LF, HF, SDNN, stress and low HRV for participants at
stress) all ages.
Filaire et al.67 2010 52(26M, 26F) 46.2±5.8 in male, State-trait anxiety inventory Short-term A reduction in the HF and HFnu HR, pNN50, RMSSD,
37.2±3.0 in female The perceived stress scale HR, pNN50, SDNN, component of HRV and an increase in HF, HFnu, LF/HF
(before and after the PMSSD, TP, LF, LFnu, the LH/HF ratio were observed at the
lecture) HF, HFnu, LF/HF end of the lecture.
Lampert et al.68 2011 163 Mean age 30 Cumulative stress/ 24 hr continious The odds of having low ULF for those in ULF, VLF, LF
adversity checklist ULF, VLF, LF, HF the higher total stress, chronic stressors,
and adverse life events groups were 2.2,
1.9, and 2.1 respectively.
Taelman et al.69 2011 28 22±1.96 (19–26) Mental task (part 1 of the Short-term HRV is sensitive to any change in mental HF, LF, LF/HF, fHF
home version of the HF, LF, LF/HF, fHF or physical state. They were able to
MENSA test) distinguish between rest, physical and
mental condition by combining different
HRVcharacteristics.
Uusitalo et al.70 2011 19 (1M, 18F) Mean age 42 Effort-reward imbalance 36 hr continious Daytime HRV correlated significantly and RMSDD, LF
(24–57) (ERI) questionnaire RMSDD, HF, LF, negatively with daytime stress feelings on
both days.
Clays et al.71 2011 653 male Range 40–55 Job Stress Questionnaire 24 hr continious The work stressor index was significantly HR, pNN50,
(JSQ) HR, pNN50, SDNN, LF, associated with lower pNN50, lower HF LF/HF
HF LF/HF HF power and a higher ratio of LF/HF
power.
Michels et al.72 2013 334 (51.2% boys) Range 5–10 Self-reported chronic Short-term Low HRV (lower parasympathetic RMSSD, LF/HF, HF
stress aspects (events, RMSSD, pNN50, LF, HF, activity) might serve as stress indicator
emotions and problems) LFnu, HFnu LF/HF in children.
Vargas-Luna 2013 57 female 48.19±5.98 (40–60) Stroop test, 3 min Short-term HRV gives a fast reaction to the LF, HF
et al.73 LF, HF psychological stress.

www.psychiatryinvestigation.org 241
HG Kim et al.
Stress and Heart Rate Variability

the connections between the brain and the heart.38 Percep-

differences between adjacent NN intervals, SDNN: standard deviation of all NN intervals, RR: rhythm-to-rhythm, TINN: triangular interpolation of RR interval histogram, SD1: the standard
SD: standard deviation, HRV: heart rate variability, HF: high-frequency band, LF: low-frequency band, HR: heart rate, M: male, F: female, pNN50: NN50 count divided by the total number of
all NN intervals, NN: normal-to-normal, TP: total power, VLF: very low frequency band, LFnu: LF norm, HFnu: HF norm, RMSSD: The square root of the mean of the sum of the squares of
Significantly changed

LF/HF, RR, SDNN,


Stressor frequency was unrelated to HRV. SDNN, RMSSD, HF
All the components of HRV were sensitive HR, RR interval, BP,
tions of threat and safety are common core elements of “stress-
HRV measures

SDNN, RMSSD,

TP, LF, HF, HFnu,

RMSSD, NN50,
LF, HF, LF/HF
ors.” Continuous perception of threats is harmful to the hu-
man body and affects the regulation of hippocampal circuits,

pNN50
endocrine systems, ANS, and others.39-42 If an organism is to

deviation of the Poincare plot perpendicular to the line-of-identity, SD2: the standard deviation of the Poincare plot along the line-of-identity, ULF: ultra low frequency band
avoid a chronic state of threat, it is essential to determine
whether threat assessment is appropriate depending on the
But individuals with more pronounced context. The prefrontal cortex (PFC) and medial PFC (mPFC),
affective reactivity to stressors also had
to stress in all the healthy individuals.

reduced with increase in the intensity


All the frequency domain indices were
lower levels of all three HRV indices
in particular, appear to be important in this appraisal pro-
cess.3,38 In safe contexts, threat representations in the amyg-

of stress except for LFnu, which


dala would be inhibited by the ventromedial PFC (vmPFC).
Major findings

A manipulation of the vmPFC, such as pharmacological in-


significantly increased. tervention, can help to inhibit subcortical threat circuits and
reduce stress responses.43-46 Studies have shown reciprocal
inhibition of the PFC and amygdala.47-49 The aim of this study
was to investigate the relationship between HRV and neuro-
genic rhythms. These inhibitory prefrontal processes can be
assessed using measures of vagal function, such as HRV. A me-
ta-analysis of HRV neuroimaging studies found a link between
PNN50, TP, LFnu, HFnu,

RMSSD, NN50, pNN50


SDNN, RMSSD, NN50,

TP, LF, HF, LFnu, HFnu,

HRV and brain regions (e.g., the ventral aspect of the mPFC)
Mean HR, Mean RR,

LF/HF, RR, SDNN,


HRV measures

(reported negative affect SDNN, RMSSD, HF

associated with reduced threat perception.3 HRV can measure


LF, HF, LF/HF

the degree of functional integration of the axes connecting


vmPFC, brainstem and peripheral anatomy and can represent
Short-term

Short-term

Short-term
Table 3. Studies of HRV reactivity to psychological stressors in healthy human participants (continued)

the degree to which it provides flexible control over ANS.

Clinical applications of HRV


In view of observations of stress-associated variation in HRV
Stroop Color Word Test

The medical students’


Stress evaluation

stress questionnaire
Telephone interviews

and existing neurobiological evidence, HRV may be used as


and minor stressful

an objective assessment of stress and mental health. Howev-


er, since psychiatric illnesses have numerous causes and
symptoms, consistent biological measurements are difficult
events)

to acquire in individuals with mental illness. Thus, a patient’s


psychological and medical history should be equally consid-
ered when interpreting HRV results. Therefore, HRV can be
(mean±SD, range)

2016 150 (72M, 78F) Medical students

considered a tool that reflects heart activity and overall auto-


Range 35–85

nomic health, rather than specific mental illnesses or disease


Age

28.52±0.71

states. Since the concept of stress includes biological and psy-


chological factors, objective and physiological evaluations as
well as self-reporting should be integrated when evaluating
stress, using HRV in clinical practice. Many studies have found
an association between mental health and HRV. However,
909
50
N

since HRV is associated with various stress factors, stress du-


ration, individual coping ability, and lifestyle habits, these
studies are difficult to interpret. Many physical conditions and
2016

2016
Year

lifestyle habits can affect HRV results, including physiologi-


cal factors (e.g., breathing, circadian rhythms, and posture),
Endukuru et al.74

non-modifiable factors (e.g., age, sex, and genetic factors),


Authors

Punita et al.76

modifiable lifestyle factors (e.g., obesity, metabolic syndrome,


75
Sin et al.

physical activity, smoking, and drinking), and other factors


[e.g., medication (e.g., anticholinergics, stimulants, and beta-

242 Psychiatry Investig 2018;15(3):235-245


HG Kim et al.

blockers)].50-55 2. Campkin M. Stress management in primary care. Fam Pract 2000;17:


98-99.
Hans Seyle1,56 proposed a three-stage stress response model.
3. Thayer JF, Ahs F, Fredrikson M, Sollers JJ, Wager TD. A meta-analysis
The first stage is the “alarm reaction stage,” in which the body of heart rate variability and neuroimaging studies: implications for
reacts to a stressor with the fight-or-flight response and acti- heart rate variability as a marker of stress and health. Neurosci Biobe-
vates the SNS. The second stage is the “resistance stage,” in hav Rev 2012;36:747-756.
4. Malik M, Camm AJ. Heart Rate Variability. Armonk, NY: Futura Pub.
which the body adapts to the stressor. During this stage, the Co.; 1995.
PNS restores many physiological functions to normal, while 5. Rajendra Acharya U, Paul Joseph K, Kannathal N, Lim CM, Suri JS.
the body focuses its resources against the stressor. Although Heart rate variability: a review. Med Biol Eng Comput 2006;44:1031-
1051.
the outward appearance of the organism seems normal, blood 6. Sztajzel J. Heart rate variability: a noninvasive electrocardiographic
glucose, cortisol, and adrenalin levels remain elevated. If a method to measure the autonomic nervous system. Swiss Med Wkly
stressor continues beyond the body’s capacity to cope, the or- 2004;134:514-522.
7. Marques AH, Silverman MN, Sternberg EM. Evaluation of stress sys-
ganism exhausts its resources, making it susceptible to disease
tems by applying noninvasive methodologies: measurements of neu-
or death. This “exhaustion stage” is reached when the acquired roimmune biomarkers in the sweat, heart rate variability and salivary
adaptation or resistance is lost. When assessing the severity cortisol. Neuroimmunomodulation 2010;17:205-208.
of a patient’s stress level in a clinical setting, HRV results should 8. Rotenberg S, McGrath JJ. Inter-relation between autonomic and HPA
axis activity in children and adolescents. Biol Psychol 2016;117:16-25.
be interpreted with this three-stage process in mind. At each 9. Porges SW. Cardiac vagal tone: a physiological index of stress. Neuro-
stage, stress causes changes in physiological function, which sci Biobehav Rev 1995;19:225-233.
are reflected in HRV changes. Due to the variety of potential 10. Curtis AL, Lechner SM, Pavcovich LA, Valentino RJ. Activation of the
locus coeruleus noradrenergic system by intracoerulear microinfusion
stressors and individual stress responses, it is essential to un- of corticotropin-releasing factor: effects on discharge rate, cortical nor-
derstand the overall autonomic context and examine a pa- epinephrine levels and cortical electroencephalographic activity. J Phar-
tient’s medical and psychological history when interpreting macol Exp Ther 1997;281:163-172.
11. Egliston KA, McMahon C, Austin MP. Stress in pregnancy and infant
the relationship between HRV and stress.
HPA axis function: conceptual and methodological issues relating to
the use of salivary cortisol as an outcome measure. Psychoneuroendo-
Discussion crinology 2007;32:1-13.
12. Berntson GG, Cacioppo JT. Heart Rate Variability: Stress and Psychi-
atric Conditions. In: Malik M, Camm J, Editors. Dynamic Electrocar-
HRV is sensitive to changes in ANS activity (i.e., changes in diography: Blackwell Publishing, 2007, p.57-64.
the SNS and PNS) associated with stress. In most studies, HRV 13. Berntson GG, Cacioppo JT, Binkley PF, Uchino BN, Quigley KS, Field-
variables changed in response to stress induced by various stone A. Autonomic cardiac control. III. Psychological stress and cardi-
ac response in autonomic space as revealed by pharmacological block-
methods. The most frequently reported factor associated with ades. Psychophysiology 1994;31:599-608.
variation in HRV variables was low parasympathetic activity, 14. Ditto B, France C. Carotid baroreflex sensitivity at rest and during psy-
which is characterized by a decrease in the HF and an increase chological stress in offspring of hypertensives and non-twin sibling
pairs. Psychosom Med 1990;52:610-620.
in the LF. HRV may be associated with the activity of a flexible
15. Heart rate variability: standards of measurement, physiological inter-
network of neural structures, which are dynamically orga- pretation and clinical use. Task Force of the European Society of Cardi-
nized in response to environmental challenges. Indeed, neu- ology and the North American Society of Pacing and Electrophysiolo-
roimaging studies suggest that HRV may be linked to reduced gy. Circulation 1996;93:1043-1065.
16. Osterrieder W, Noma A, Trautwein W. On the kinetics of the potassi-
threat perception, mediated by cortical regions (e.g., the ven- um channel activated by acetylcholine in the S-A node of the rabbit
tral aspect of the mPFC) involved in the appraisal of stressful heart. Pflügers Archiv 1980;386:101-109.
situations. In clinical situations, HRV can be considered a tool 17. Noma A, Trautwein W. Relaxation of the ACh-induced potassium cur-
rent in the rabbit sinoatrial node cell. Pflugers Arch 1978;377:193-200.
that reflects heart activity and overall autonomic health, rath- 18. Brown HF, DiFrancesco D, Noble SJ. How does adrenaline accelerate
er than specific mental illnesses or disease states. Thus, when the heart? Nature 1979;280:235-236.
evaluating the relationship between stress and HRV, it is es- 19. Akselrod S, Gordon D, Madwed JB, Snidman NC, Shannon DC, Co-
hen RJ. Hemodynamic regulation: investigation by spectral analysis.
sential to consider the overall autonomic context as well as
Am J Physiol 1985;249:H867-H875.
the patient’s medical and psychological history. 20. Levy MN. Sympathetic-parasympathetic interactions in the heart. Circ
Res 1971;29:437-445.
Acknowledgements 21. Kjellgren O, Gomes JA. Heart rate variability and baroreflex sensitivity
This work was supported by the National Research Foundation of Korea in myocardial infarction. Am Heart J 1993;125:204-215.
(NRF) grant funded by the Korean government (MSIP: Ministry of Sci- 22. Caruana-Montaldo B, Gleeson K, Zwillich CW. The control of breath-
ence, ICT, and Future Planning) (No. 216C000671). ing in clinical practice. Chest 2000;117:205-225.
23. Tian K, Qin J, Huang L, Long M, Wu J, Yu S, et al. [The effect of aerobic
and anaerobic endurance training on the regulating function of auto-
REFERENCES
nomic nervous system and its significance]. Sheng Wu Yi Xue Gong
1. Selye H. The Stress of Life. New York: McGraw-Hill; 1956. Cheng Xue Za Zhi 2006;23:1020-1023.

www.psychiatryinvestigation.org 243
Stress and Heart Rate Variability

24. Aubert AE, Seps B, Beckers F. Heart rate variability in athletes. Sports 48. Milad MR, Wright CI, Orr SP, Pitman RK, Quirk GJ, Rauch SL. Recall
Med 2003;33:889-919. of fear extinction in humans activates the ventromedial prefrontal cor-
25. Vanderlei LC, Pastre CM, Hoshi RA, Carvalho TD, Godoy MF. Basic tex and hippocampus in concert. Biol Psychiatry 2007;62:446-454.
notions of heart rate variability and its clinical applicability. Rev Bras 49. Delgado MR, Nearing KI, LeDoux JE, Phelps EA. Neural circuitry un-
Cir Cardiovasc 2009;24:205-217. derlying the regulation of conditioned fear and its relation to extinc-
26. Ludwig C. Beitrage zur Kenntniss des Einflusses der Respriations bewe- tion. Neuron 2008;59:829-838.
gungen auf den Blutlauf im Aortensysteme. Arch Anat Physiol 1847;13: 50. Romanowicz M, Schmidt JE, Bostwick JM, Mrazek DA, Karpyak VM.
242-3027. Changes in heart rate variability associated with acute alcohol consump-
27. Donder FC. Zur Physiologies des Nervus vagus. Pfluegers Arch Ges tion: current knowledge and implications for practice and research. Al-
Physiol 1868;1:331-361. cohol Clin Exp Res 2011;35:1092-1105.
28. Bainbridge FA. The relation between respiration and the pulse-rate. J 51. Spaak J, Tomlinson G, McGowan CL, Soleas GJ, Morris BL, Picton P,
Physiol 1920;54:192-202. et al. Dose-related effects of red wine and alcohol on heart rate variabil-
29. Berntson GG, Bigger JT Jr, Eckberg DL, Grossman P, Kaufmann PG, ity. Am J Physiol Heart Circ Physiol 2010;298:H2226-H2231.
Malik M, et al. Heart rate variability: origins, methods, and interpre- 52. Dinas PC, Koutedakis Y, Flouris AD. Effects of active and passive to-
tive caveats. Psychophysiology 1997;34:623-648. bacco cigarette smoking on heart rate variability. Int J Cardiol 2013;163:
30. Wolf S. The end of the rope: the role of the brain in cardiac death. Can 109-115.
Med Assoc J 1967;97:1022-1025. 53. Felber Dietrich D, Ackermann-Liebrich U, Schindler C, Barthelemy JC,
31. Kleiger RE, Stein PK, Bosner MS, Rottman JN. Time domain measure- Brandli O, Gold DR, et al. Effect of physical activity on heart rate vari-
ments of heart rate variability. Cardiol Clin 1992;10:487-498. ability in normal weight, overweight and obese subjects: results from
32. Hnatkova K, Copie X, Staunton A, Malik M. Numeric processing of the SAPALDIA study. Eur J Appl Physiol 2008;104:557-565.
Lorenz plots of R-R intervals from long-term ECGs. Comparison with 54. Min KB, Min JY, Paek D, Cho SI. The impact of the components of met-
time-domain measures of heart rate variability for risk stratification abolic syndrome on heart rate variability: using the NCEP-ATP III and
after myocardial infarction. J Electrocardiol 1995;28(Suppl):74-80. IDF definitions. Pacing Clin Electrophysiol 2008;31:584-591.
33. Ori Z, Monir G, Weiss J, Sayhouni X, Singer DH. Heart rate variability. 55. Altuncu ME, Baspinar O, Keskin M. The use of short-term analysis of
Frequency domain analysis. Cardiol Clin 1992;10:499-537. heart rate variability to assess autonomic function in obese children and
34. Malliani A, Pagani M, Lombardi F, Cerutti S. Cardiovascular neural its relationship with metabolic syndrome. Cardiol J 2012;19:501-506.
regulation explored in the frequency domain. Circulation 1991;84:482- 56. Selye H. Stress in Health and Disease. Boston: Butterworths; 1976.
492. 57. Kaegi DM, Halamek LP, Van Hare GF, Howard SK, Dubin AM. Effect
35. Sloan RP, Shapiro PA, Bagiella E, Boni SM, Paik M, Bigger JT Jr, et al. of mental stress on heart rate variability: validation of simulated oper-
Effect of mental stress throughout the day on cardiac autonomic con- ating and delivery room training modules. Pediatr Res 1999;45:77A.
trol. Biol Psychol 1994;37:89-99. 58. Delaney JP, Brodie DA. Effects of short-term psychological stress on
36. Kageyama T, Nishikido N, Kobayashi T, Kurokawa Y, Kaneko T, Kabu- the time and frequency domains of heart-rate variability. Percept Mot
to M. Self-reported sleep quality, job stress, and daytime autonomic ac- Skills 2000;91:515-524.
tivities assessed in terms of short-term heart rate variability among 59. Vrijkotte TG, van Doornen LJ, de Geus EJ. Effects of work stress on
male white-collar workers. Ind Health 1998;36:263-272. ambulatory blood pressure, heart rate, and heart rate variability. Hyper-
37. Dimitriev DA, Saperova EV. [Heart rate variability and blood pressure tension 2000;35:880-886.
during mental stress]. Ross Fiziol Zh Im I M Sechenova 2015;101:98-107. 60. Dishman RK, Nakamura Y, Garcia ME, Thompson RW, Dunn AL,
38. Thayer JF, Lane RD. Claude Bernard and the heart-brain connection: Blair SN. Heart rate variability, trait anxiety, and perceived stress among
further elaboration of a model of neurovisceral integration. Neurosci physically fit men and women. Int J Psychophysiol 2000;37:121-133.
Biobehav Rev 2009;33:81-88. 61. Lucini D, Norbiato G, Clerici M, Pagani M. Hemodynamic and auto-
39. Seeman TE, McEwen BS, Rowe JW, Singer BH. Allostatic load as a nomic adjustments to real life stress conditions in humans. Hyperten-
marker of cumulative biological risk: MacArthur studies of successful sion 2002;39:184-188.
aging. Proc Natl Acad Sci U S A 2001;98:4770-4775. 62. Hjortskov N, Rissén D, Blangsted AK, Fallentin N, Lundberg U, Søgaard
40. Sapolsky RM. Why stress is bad for your brain. Science 1996;273:749- K. The effect of mental stress on heart rate variability and blood pressure
750. during computer work. Eur J Appl Physiol 2004;92:84-89.
41. McEwen BS. From molecules to mind. Stress, individual differences, 63. Kang MG, Koh SB, Cha BS, Park JK, Woo JM, Chang SJ. Association
and the social environment. Ann N Y Acad Sci 2001;935:42-49. between job stress on heart rate variability and metabolic syndrome in
42. Chrousos GP, Kino T. Interactive functional specificity of the stress and shipyard male workers. Yonsei Med J 2004;45:838-846.
immune responses: the ying, the yang, and the defense against 2 major 64. Hintsanen M, Elovainio M, Puttonen S, Kivimaki M, Koskinen T, Raita-
classes of bacteria. J Infect Dis 2005;192:551-555. kari OT, et al. Effort-reward imbalance, heart rate, and heart rate vari-
43. Quirk GJ, Beer JS. Prefrontal involvement in the regulation of emotion: ability: the cardiovascular risk in young finns study. Int J Behav Med
convergence of rat and human studies. Curr Opin Neurobiol 2006;16: 2007;14:202-212.
723-727. 65. Orsila R, Virtanen M, Luukkaala T, Tarvainen M, Karjalainen P, Viik J,
44. Milad M, Vidal-Gonzalez I, Quirk G. Electrical stimulation of medial et al. Perceived mental stress and reactions in heart rate variability- a
prefrontal cortex reduces conditioned fear in a temporally specific man- pilot study among employees of an electronics company. Int J Occup
ner. Behav Neurosci 2004;118:389-394. Saf Ergon 2008;14:275-283.
45. Milad MR, Quirk GJ. Neurons in medial prefrontal cortex signal mem- 66. Chandola T, Britton A, Brunner E, Hemingway H, Malik M, Kumari
ory for fear extinction. Nature 2002;420:70-74. M, et al. Work stress and coronary heart disease: what are the mecha-
46. Amat J, Paul E, Watkins LR, Maier SF. Activation of the ventral medial nisms? Eur Heart J 2008;29:640-648.
prefrontal cortex during an uncontrollable stressor reproduces both 67. Filaire E, Portier H, Massart A, Ramat L, Teixeira A. Effect of lecturing
the immediate and long-term protective effects of behavioral control. to 200 students on heart rate variability and alpha-amylase activity. Eur
Neuroscience 2008;154:1178-1186. J Appl Physiol 2010;108:1035-1043.
47. Schiller D, Levy I, Niv Y, LeDoux JE, Phelps EA. From fear to safety and 68. Lampert R, Tuit K, Sinha R. Chronic stress and adverse life events are
back: reversal of fear in the human brain. J Neurosci 2008;28:11517- associated with depressed autonomic function as measured by heart
11525. rate variability. Circulation 2011;124:A10441.

244 Psychiatry Investig 2018;15(3):235-245


HG Kim et al.

69. Taelman J, Vandeput S, Gligorijevic I, Spaepen A, Van Huffel S. Time- diac Response to Psychological Stress by Short-Term ECG Recordings:
frequency heart rate variability characteristics of young adults during Heart Rate Variability and Detrended Fluctuation Analysis. In: Long
physical, mental and combined stress in laboratory environment. Conf M, editor. World Congress on Medical Physics and Biomedical Engi-
Proc IEEE Eng Med Biol Soc 2011;2011:1973-1976. neering May 26-31, 2012, Beijing, China. Berlin, Heidelberg: Springer
70. Uusitalo A, Mets T, Martinmaki K, Mauno S, Kinnunen U, Rusko H. Berlin Heidelberg; 2013, p.333-335.
Heart rate variability related to effort at work. Appl Ergon 2011;42:830- 74. Endukuru CK, Tripathi S. Evaluation of cardiac responses to stress in
838. healthy individuals- a non invasive evaluation by heart rate variability
71. Clays E, De Bacquer D, Crasset V, Kittel F, de Smet P, Kornitzer M, et and stroop test. Int J Sci Res 2016;5:286-289.
al. The perception of work stressors is related to reduced parasympa- 75. Sin NL, Sloan RP, McKinley PS, Almeida DM. Linking daily stress
thetic activity. Int Arch Occup Environ Health 2011;84:185-191. processes and laboratory-based heart rate variability in a national
72. Michels N, Sioen I, Clays E, De Buyzere M, Ahrens W, Huybrechts I, sample of midlife and older adults. Psychosom Med 2016;78:573-582.
et al. Children’s heart rate variability as stress indicator: association 76. Punita P, Saranya K, Kumar SS. Gender difference in heart rate vari-
with reported stress and cortisol. Biol Psychol 2013;94:433-440. ability in medical students and association with the level of stress. Natl
73. Vargas-Luna M, Huerta-Franco MR, Montes JB. Evaluation of the Car- J Physiol Pharm Pharmacol 2016;6:431-437.

www.psychiatryinvestigation.org 245

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