The Effect of Non-Pharmacological Treatment for Psychophysiological Insomnia on Cardiovascular Autonomic Regulation Assessed Using Heart Rate Variability

Abstract

Background and Objective Cardiac autonomic regulation is altered in psychophysiological insomnia. We evaluated whether successful non-pharmacological treatment for psychophysiological insomnia could stabilize cardiac autonomic regulation. Methods Subjects were 26 patients with psychophysiological insomnia who underwent four sessions of non-pharmacological treatment. We measured subjects’ heart rate variability (HRV) at baseline and post-treatment. Based on the post-treatment Insomnia Severity Index (ISI) score, we categorized subjects into responder (n = 16, post-ISI < 8) and non-responder (n = 10) groups. Results At baseline, we found no significant differences between responder and non-responder groups in age, sex, body mass index, insomnia severity, and features of HRV time and frequency domains. In the responders group, we observed significant increases in the standard deviation of the normal sinus to normal sinus interval (SDNN) (p = 0.02), the proportion of the number of interval differences of successive normal sinus to normal sinus intervals greater than 50 ms by the total number of normal sinus to normal sinus intervals (pNN50) (p = 0.02), total power (p < 0.01), and very low frequency (p = 0.02) and a significant decrease in low frequency (p = 0.04) after successful non-pharmacological treatment for insomnia. However, in the non-responders group, there were no significant changes in HRV features after treatment. Conclusions The successful non-pharmacological treatment of insomnia may reduce the risk of cardiovascular complications in patients with psychophysiological insomnia.

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pISSN 2093-9175 / eISSN 2233-8853
10 Copyright
©
2011 The Korean Society of Sleep Medicine
ORIGINAL ARTICLE
INTRODUCTION
Insomnia is defined as difficulty initiating or maintaining sleep, waking up too early, or
experiencing non-restorative sleep. Several studies have shown that insomnia is associated with
various medical conditions, including hypertension, diabetes, and congestive heart failure.1,2
Furthermore, both insomnia and short sleep duration are associated with increased risk of car-
diovascular complications and high mortality rates.3,4 Studies have examined the relationship
between insomnia and the risk of cardiovascular complications by measuring heart rate va-
riability (HRV),5-7 which is a non-invasive method for assessing cardiovascular risk.8 is re-
search showed altered cardiac autonomic regulation, as measured using HRV, in patients with
psychophysiological insomnia.
Although chronic sleep disturbance may increase the risk of serious health problems, whe-
ther improving insomnia will improve health is debatable.9 One recent study found that treat-
ing insomnia with hypnotics or non-pharmacological treatment improved patients’ quality of
life (QOL).10-13 However, other studies have reported hypnotics decreased the physical aspects
of QOL.11 Furthermore, long-term use of hypnotics is associated with various adverse events
and, potentially, dependency.
Non-pharmacological therapy is a rst-line treatment for primary insomnia,14 and it com-
prises behavioral, cognitive, and educational components. Most studies have reported that non-
Received: February 4, 2011
Revised: March 24, 2011
Accepted: April 1, 2011
Correspondence
Seockhoon Chung, MD, PhD
Department of Psychiatry,
University of Ulsan College of Medicine,
Asan Medical Center,
86 Asanbyeongwon-gil, Songpa-gu,
Seoul 138-736, Korea
Tel +82-2-3010-3411
Fax +82-2-485-8381
E-mail schung@amc.seoul.kr
e Eect of Non-Pharmacological Treatment
for Psychophysiological Insomnia on Cardiovascular Autonomic
Regulation Assessed Using Heart Rate Variability
Seockhoon Chung, MD, PhD, Hoyoung An, MD, Jangho Park, MD, Hyojung Kim, RN
Department of Psychiatry, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
Background and ObjectiveaaCardiac autonomic regulation is altered in psychophysiological insomnia. We evaluated whether success-
ful non-pharmacological treatment for psychophysiological insomnia could stabilize cardiac autonomic regulation.
MethodsaaSubjects were 26 patients with psychophysiological insomnia who underwent four sessions of non-pharmacological treatment.
We measured subjects’ heart rate variability (HRV) at baseline and post-treatment. Based on the post-treatment Insomnia Severity Index
(ISI) score, we categorized subjects into responder (n = 16, post-ISI < 8) and non-responder (n = 10) groups.
ResultsaaAt baseline, we found no signicant dierences between responder and non-responder groups in age, sex, body mass index,
insomnia severity, and features of HRV time and frequency domains. In the responders group, we observed signicant increases in the
standard deviation of the normal sinus to normal sinus interval (SDNN) (p = 0.02), the proportion of the number of interval dierences
of successive normal sinus to normal sinus intervals greater than 50 ms by the total number of normal sinus to normal sinus intervals
(pNN50) (p = 0.02), total power (p < 0.01), and very low frequency (p = 0.02) and a signicant decrease in low frequency (p = 0.04) aer
successful non-pharmacological treatment for insomnia. However, in the non-responders group, there were no signicant changes in
HRV features aer treatment.
Conclusionsaae successful non-pharmacological treatment of insomnia may reduce the risk of cardiovascular complications in pa-
tients with psychophysiological insomnia. Sleep Med Res 2011;2:10-15
Key WordsaaHeart rate variability, Insomnia, Cardiovascular complication, Cognitive-behavioral therapy.
Sleep Med Res 2011;2:10-15
online © ML Comm

Chung S, et al.
www.sleepmedres.org 11
pharmacological treatment alone, or in combination with ph-
armacotherapy, was more eective, with longer lasting eects,
than was pharmacotherapy alone.15-17 Moreover, non-pharma-
cological treatment is safer than medication for treating inso-
mnia. In the present study, we hypothesized that insomnia
treatment would reduce the risk of cardiovascular compli-
cations, as measured by HRV. is study aimed to test whether
successful non-pharmacological treatment of psychophysiolo-
gical insomnia would normalize cardiac autonomic activity.
METHODS
Subjects
Between May 2009 and November 2010, we recruited subjects
from the sleep clinic at the Department of Psychiatry in the Asan
Medical Center. All patients had been newly diagnosed with psy-
chophysiological insomnia according to the diagnostic criteria
of the International Classication of Sleep Disorders-2nd edit-
ion.18 e exclusion criteria were 1) current use of sleeping pills,
psychotropic agents, antihypertensive or antihyperlipidemic
agents, or medication to treat diabetes; 2) presence of a concur-
rent major psychiatric condition, such as major depressive dis-
order or anxiety disorder; and 3) the presence of other, concur-
rent sleep disorders, such as circadian rhythm sleep disorder,
restless legs syndrome (RLS), periodic limb movements during
sleep (PLMS) or obstructive sleep apnea syndrome (OSAS). All
prospective participants underwent a full history and psychia-
tric examination by a psychiatrist (sleep specialist). e subjects
were asked to complete a sleep diary for a week. To assess pa-
tients for sleep disorders such as RLS, PLMS, and OSAS, we ut-
ilized sleep questionnaires and/or reports from the patients
and their families. We administered the HRV test and various
rating scales to the subjects at baseline. ese rating scales were
the Insomnia Severity Index (ISI),19 the Pittsburg Sleep Quality
Scale (PSQI),20 the Epworth Sleepiness Scale (ESS),21 the ab-
breviated version of the Dysfunctional Beliefs and Attitudes
about Sleep Scale (DBAS-16),22 the Hospital Anxiety and De-
pression Scale (HADS),23 and the Pre-Sleep Arousal Scale (PS-
AS).24 e subjects underwent four non-pharmacological treat-
ment sessions over an 8-week period, aer which we repeated
the rating scales and HRV test. is protocol was approved by
the Institutional Review Board of the Asan Medical Center.
Non-Pharmacological Treatment
In the present study, cognitive-behavioral treatment (CBT)
consisted of four sessions, one every other week over an eight-
week period. A psychiatrist (sleep specialist) and a specialized
nurse conducted all sessions, individualized for each subject.
e rst was the baseline session, in which we assessed subjects
for sleep and psychiatric disorders and taught them about psy-
chophysiological insomnia and sleep hygiene. Additionally, the
subjects were instructed to continue their sleep diaries. During
the second session, we analyzed each subject’s sleep diary and
conducted their sleep restriction therapy based on information
from the analysis. Each subject also received instructions about
abdominal breathing. During the third session, we assessed
changes in the subject’s sleeping patterns and cognition due to
sleep restriction. The subject then received stimulus control
therapy and instruction in progressive muscular relaxation. In
the last session, we reviewed the changes that occurred during
the previous three sessions and gave the subjects paradoxical
intention and cognitive therapy and instructions on guided
imagery.
Heart Rate Variability Measures
Each subject’s HRV was recorded for 5 min aer a rest period
of at least 10 min. Electrocardiogram (EKG) signals were con-
tinuously monitored and simultaneously sampled using an EKG
monitor (LXCJ103, Laxtha, Daejeon, Korea) and the data were
analyzed using a data analyzer (CANS 3000, Laxtha). e HRV
measurements followed the standards that the Task Force of
the European Society of Cardiology and the North American
Society of Pacing and Electrophysiology suggested in 1996.25
We calculated spectral power for four frequency bands: very
low frequency (VLF, ≤ 0.04 Hz), low frequency (LF, 0.04-0.15
Hz), high frequency (HF, 0.15-0.4 Hz), and total power (0-0.4
Hz) and performed a natural logarithmic transformation on
these HRV parameters. Next, we calculated the LF to HF ratio,
expressing it as LF/HF. The time domain variables we cal-
culated were heart rate, HRV index, the standard deviation of
the normal sinus to normal sinus interval (SDNN), the square
root of the mean of the sum of the squares of dierences be-
tween adjacent normal-to-normal intervals (RMSSD) the st-
andard deviation of successive differences between adjacent
normal-to-normal intervals (SDSD), and the proportion of the
number of interval differences of successive normal sinus to
normal sinus intervals greater than 50 ms by the total number
of normal sinus to normal sinus interals (pNN50).
Statistical Analysis
To compare clinical characteristics between subjects in the
CBT responders group and those in the non-responders group,
we employed student’s t-test and chi-square analyses. We as-
sessed within-group changes using paired t-tests. Statistical sig-
nicance was set at p < 0.05 for two-tailed tests. e Statistical
Package for the Social Sciences (SPSS), version 12.0 K (SPSS Inc.,
Chicago, IL, USA), was used to conduct these statistical tests.
RESULTS
We enrolled 46 patients with psychophysiological insomnia
who were not taking sleeping pills, psychotropic agents, antihy-

12 Sleep Med Res 2011;2:10-15
Heart Rate Variability in Insomnia Patients
pertensive or antihyperlipidemic drugs, or diabetes medication.
Of these 46 subjects, we excluded 20 who did not complete the
four-session CBT regimen. We divided the remaining 26 sub-
jects into CBT responders (n = 16) and CBT non-responders (n
= 10) based on their post-treatment ISI score (dening “res-
ponding” as having a post-treatment ISI < 8).
No significant differences in age, body mass index (BMI),
sex, or blood pressure were found between the CBT responder
and CBT non-responder groups (Table 1). Likewise, we found
no signicant between-group dierences in baseline reported
sleep latency and sleep eciency, ISI, PSQI, ESS, PSAS, DBAS-
16, and HADS scores. Furthermore, the baseline time- and fre-
quency-domain HRV variables did not dier signicantly be-
tween groups (Table 2). Following treatment, the CBT res-
ponder group’s time domain variables (SDNN, p = 0.02; pNN50,
p = 0.02) and certain frequency domain variables (total power,
p < 0.01; VLF, p = 0.02) signicantly increased (Table 3) while LF
(p < 0.04) signicantly decreased (Table 4) and HF (p = 0.051)
marginally increased. However, we observed no significant
changes in time or frequency domain variables in the CBT non-
responder group (Table 3 and 4).
DISCUSSION
In the present study, SDNN and pNN50 time domain va-
Table 1. Demographic and clinical characteristics of the subjects at baseline
CBT responders (n=16) CBT non-responders (n=10) p-value
Age (yr) 057.9 ± 10.9 59.4 ± 7.4 0.71
Body mass index (kg/m2) 25.1 ± 3.8 23.6 ± 4.6 0.41
Sex (M/F) 6/10 4/6 0.90
Systolic blood pressure (mmHg) 119.3 ± 6.70120.2 ± 9.100.75
Diastolic blood pressure (mmHg) 82.5 ± 5.8 82.6 ± 8.7 0.68
Sleep latency (min) 102.9 ± 70.5 101.0 ± 67.1 0.89
Sleep eciency (%) 077.7 ± 18.9 070.8 ± 26.5 0.29
ISI score 19.5 ± 4.0 18.1 ± 4.9 0.57
PSQI scores 13.0 ± 4.0 14.9 ± 4.6 0.32
ESS score 06.9 ± 4.6 04.4 ± 3.9 0.20
DBAS-16 score 080.9 ± 34.9 086.8 ± 29.6 0.69
PSAS score 045.0 ± 12.3 043.7 ± 11.6 0.82
HADS score 15.1 ± 5.9 19.8 ± 8.1 0.13
CBT: cognitive-behavioral therapy, ISI: Insomnia Severity Index, PSQI: Pittsburg Sleep Quality Index, ESS: Epworth Sleepiness Scale, DBAS-
16: Dysfunctional Belief and Attitudes about Sleep-16 items, PSAS: Pre-Sleep Arousal Scale, HADS: Hospital Anxiety Depression Scale.
Table 2. Baseline heart rate variability between CBT responder and non-responder groups
CBT responders (n=16) CBT non-responders (n=10) p-value
HRV index 9.6 ± 3.5 8.4 ± 3.6 0.42
RR intervals (s) 0.91 ± 0.11 0.84 ± 0.17 0.24
HR 66.9 ± 10.7 73.9 ± 14.9 0.17
SDNN (ms) 29.6 ± 12.5 26.3 ± 13.1 0.54
RMSSD (ms) 18.1 ± 7.6017.3 ± 13.1 0.85
SDSD (ms) 22.0 ± 9.0022.2 ± 15.3 0.96
pNN50 (%) 23.0 ± 16.6 18.9 ± 18.6 0.57
Total power 6.4 ± 0.9 6.3 ± 0.8 0.87
VLF 5.9 ± 1.0 5.6 ± 1.0 0.45
LF 5.4 ± 0.8 5.3 ± 0.5 0.77
HF 4.3 ± 1.1 4.7 ± 0.8 0.41
LF/HF 1.2 ± 0.4 1.1 ± 0.2 0.41
CBT: cognitive-behavioral therapy, HRV: heart rate variability, HR: heart rate, SDNN: standard deviation of all normal to normal RR intervals,
RMSSD: square root of the mean of the sum of the squares of successive NN interval dierences, SDSD: standard deviation of successive dif-
ferences between adjacent normal-to-normal intervals, pNN50: proportion of number of intervals >50 ms dierent from preceding interval,
VLF: very low frequency, LF: low frequency, HF: high frequency.

Chung S, et al.
www.sleepmedres.org 13
riables increased significantly following successful non-phar-
macological treatment. Furthermore, following treatment the
frequency domain variables of total power and VLF power sig-
nificantly increased, while LF power significantly decreased.
Our results suggest that successful non-pharmacological treat-
ment for insomnia may reduce the risk of cardiovascular com-
plications.
Research indicates decreased HRV results from increased
sympathetic activation and reduced parasympathetic activat-
ion.25 Furthermore, studies have shown decreases in time domain
variables, such as SDNN, RMSSD, and pNN50, occur in associ-
ation with an increased risk of cardiovascular complications.8
Of the frequency domain variables, HF correlates highly with
parasympathetic tone, and LF reects sympathetic activity. In
contrast, the physiology underlying VLF power is poorly un-
derstood.26,27
e human response to chronic sleep disturbance is similar
to that for stress and depression.28,29 Sleep deprivation may
cause neurotransmitter and neuroendocrine system changes,
which the autonomic sympatho-adrenal system and the hy-
pothalamic-pituitary-adrenal axis mediate.30 Moreover, inso-
mnia or sleep restriction correlates with an increased risk of
cardiovascular complications.31 Researchers have demonstrated
this relationship via the HRV test,5,32-34 an established non-
invasive tool for quantifying sympathetic and parasympathetic
modulation. Healthy, sleep-deprived subjects show evidence of
changes in sympathetic and parasympathetic modulation.35,36
Reportedly, SDNN decreases signicantly during sleep in pa-
tients with insomnia,5 and a study found lower wake-to-sleep
heart rates and lower SDNN in subjects with subjectively-re-
ported insomnia.34 ese ndings indicate patients with inso-
mnia have detectable, constant sympathetic hyperactivation.33
Furthermore, spectral analysis has revealed significantly in-
creased LF power or signicantly decreased HF power in pa-
tients with insomnia.5,32 ese data indicate chronic sleep dis-
turbance correlates with increased sympathetic nervous system
activity and an increased risk for the development of cardio-
vascular disorders.
In the present study, we observed signicant HRV changes
in the CBT responders group but no changes in the non-respon-
der group, suggesting successful insomnia treatment reduces
sympathetic hyperactivity and stimulates parasympathetic
activity. Several studies have investigated hypnotics’ eects on
HRV,37,38 though their results were not conclusive. No study has
examined the eect of non-pharmacological insomnia treatment
on HRV in patients with psychophysiological insomnia. Non-
pharmacological treatment in the present study included sleep
restriction, stimulus control, cognitive therapy, and relaxation
training. We found non-pharmacological insomnia treatment
significantly affected HRV of patients in the CBT responder
group but did not signicantly inuence HRV in non-respon-
ders. Our ndings suggest that successful insomnia treatment
may improve patient health. ese ndings also provide evid-
ence of non-pharmacological treatment’s impact. Electroence-
Table 3. Changes in time domain variables of heart rate variability
CBT responders (n=16) CBT non-responders (n=10)
Baseline Aer CBT p-value Baseline Aer CBT p-value
HRV index 9.6 ± 3.5 8.4 ± 3.6 0.42 8.4 ± 3.6 08.9 ± 2.4 0.59
RR intervals (s) 0.91 ± 0.11 0.93 ± 0.13 0.71 0.84 ± 0.17 00.84 ± 0.13 0.92
HR 66.9 ± 10.7 66.1 ± 9.600.79 73.9 ± 14.9 073.4 ± 13.3 0.89
SDNN (ms) 29.6 ± 12.5 35.9 ± 8.800.02 26.3 ± 13.1 28.9 ± 9.1 0.58
RMSSD (ms) 18.1 ± 7.6019.6 ± 9.400.51 17.3 ± 13.1 124.3 ± 16.1 0.32
SDSD (ms) 22.0 ± 9.0024.9 ± 11.3 0.24 22.2 ± 15.3 18.8 ± 4.8 0.50
pNN50 (%) 23.0 ± 16.6 31.7 ± 10.6 0.02 18.9 ± 18.6 021.9 ± 12.6 0.63
CBT: cognitive-behavioral therapy, HRV: heart rate variability, HR: heart rate, SDNN: standard deviation of all normal to normal RR intervals,
RMSSD: square root of the mean of the sum of the squares of successive NN interval dierences, SDSD: standard deviation of successive dif-
ferences between adjacent normal-to-normal intervals, pNN50: proportion of number of intervals > 50 ms dierent from preceding interval.
Table 4. Changes in frequency domain variables of heart rate variability
CBT responders (n=16) CBT non-responders (n=10)
Baseline Aer CBT p-value Baseline Aer CBT p-value
Total power 6.4 ± 0.6 7.0 ± 0.5 < 0.01 6.3 ± 0.8 6.6 ± 0.5 0.42
VLF 5.9 ± 1.0 6.4 ± 0.6 0.02 5.6 ± 1.0 5.9 ± 0.7 0.53
LF 5.4 ± 0.8 4.8 ± 1.0 0.04 5.3 ± 0.5 4.9 ± 1.0 0.31
HF 4.3 ± 1.1 4.8 ± 0.8 0.051 4.7 ± 0.8 4.4 ± 0.8 0.26
LF/HF 1.2 ± 0.4 1.2 ± 0.3 0.76 1.1 ± 0.2 1.1 ± 0.3 0.84
CBT: cognitive-behavioral therapy, VLF: very low frequency, LF: low frequency, HF: high frequency.

14 Sleep Med Res 2011;2:10-15
Heart Rate Variability in Insomnia Patients
phalogram spectral analysis studies have conrmed that CBT
is an eective insomnia treatment.39,40 Moreover, reportedly non-
pharmacological treatment of post-traumatic stress disorder
and other anxiety disorders41,42 has eectively stabilized HRV.
Further study is needed on how non-pharmacological treatment
aects hyperarousal states in insomnia and other psychiatric
disorders.
e present study is limited by its small sample size. It may
have been underpowered for detecting signicant group dif-
ferences. e small sample size resulted from our exclusion of
patients taking medications, including sleeping pills, psycho-
tropic agents, and antihypertensive or antihyperlipidemic
agents, to rule out any medication eects on cardiac autonomic
activity.38,43 Another study limitation is the lack of normal con-
trol subjects. We did not perform nocturnal polysomnography
(NPSG) in this study. A primary objective of NPSG is the ex-
clusion of subjects with sleep disorders, such as RLS, PLMS, and
OSAS. OSAS in particular can influence cardiac autonomic
activity.44 However, patients with psychophysiological insom-
nia do not routinely undergo NPSG, and we found no signi-
cant between-group dierences in OSAS risk factors, such as
sex, age, and BMI. In conclusion, the successful non-pharma-
cological treatment of insomnia may reduce the risk of cardio-
vascular complications in patients with psychophysiological
insomnia.
Acknowledgements
This study was supported by a education & research fund (2010-
488) from the Asan Institute for Life Sciences, Seoul, Korea.
Conflicts of Interest
e authors have no nancial conicts of interest.
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