RESEARCH ARTICLE

Arterial baroreflex dysfunction in major depressive disorder

Mats Johansson • Anna Ehnvall • Peter Friberg •

Anna Myredal

Received: 4 August 2009 / Accepted: 5 January 2010 / Published online: 2 February 2010

� Springer-Verlag 2010

Abstract

Objectives Patients treated for major depressive disorder

are at increased risk for sudden cardiac death. Impaired

arterial baroreflex function has been associated with ven-

tricular arrhythmias. Our hypothesis was that arterial bar-

oreflex dysfunction prevails in major depressive disorder

and that electroconvulsive therapy in conjunction to med-

ical therapy would improve both depressive symptoms and

baroreflex function.

Methods Thirty-three patients with major depressive

disorder who were treated in hospital were studied before

and after electroconvulsive treatment. Eighteen patients

underwent follow-up investigations 6 months after dis-

charge. ECG and beat-to-beat blood pressures were recor-

ded continuously. Arterial baroreflex sensitivity (BRS) and

effectiveness index were calculated. Twenty healthy sub-

jects were examined for comparison.

Results Heart rate and systolic blood pressures were ele-

vated (P \ 0.01 for all) in depressive patients before

treatment when compared with healthy subjects, whereas

arterial BRS and baroreflex effectiveness were reduced

(10 ± 7 vs. 15 ± 5 ms/mmHg and 0.35 ± 0.20 vs. 0.48 ±

0.14, P \ 0.01 for both). Whereas depressive symptoms

decreased after treatment (P \ 0.05), blood pressures, heart

rate, arterial BRS, and effectiveness remained unchanged. At

follow-up, 6 months after discharge all variables were

unchanged when compared with values obtained at discharge.

Conclusion Both the sensitivity and the number of times the

arterial baroreflex is being active are reduced in major

depressive disorder and this baroreflex dysfunction may pre-

vail long-term when depressive symptoms have improved.

Keywords Depression � Baroreflex sensitivity �Effectiveness index � Blood pressure

Introduction

Subjects in the general population who have depressive

symptoms and patients with major depressive disorders are

both at increased risk for cardiovascular diseases [1]. There

are several mechanisms by which depression may act to

increase the risk of cardiovascular disease. Endothelial dys-

function and low-grade inflammation have been associated to

major depressive diseases and hence, considered as plausible

mechanisms linking it to cardiovascular morbidity [2, 3].

Furthermore, published data suggest that clinical depression

predicts the risk of sudden cardiac death independently of

established risk factors such as diabetes, myocardial infarction

or congestive heart failure [4]. Patients with clinical depres-

sion who were referred to a mental health clinic had higher risk

of out-of-hospital cardiac arrest when compared with other

patients suggesting a further risk increase for sudden cardiac

death in severely depressed subjects [5].

M. Johansson (&) � P. Friberg � A. Myredal

Department of Clinical Physiology,

Sahlgrenska University Hospital,

413 45 Goteborg, Sweden

e-mail: matsjohans@telia.com; mats.johansson@lthalland.se

A. Ehnvall

Psychiatric Out-Patient Clinic, Varberg, Sweden

M. Johansson � A. Myredal

Department of Internal Medicine,

Varberg Hospital, Varberg, Sweden

A. Ehnvall

Institute of Clinical Neuroscience,

Sahlgrenska University Hospital,

Goteborg, Sweden

123

Clin Auton Res (2010) 20:235–240

DOI 10.1007/s10286-010-0053-y

A decreased heart rate response to a given blood pres-

sure change, arterial baroreflex sensitivity (BRS), has been

associated with an increased risk of cardiac death or non-

fatal cardiac arrests after a myocardial infarction [6]. We

have recently reported that the baroreflex effectiveness

index (BEI), reflecting the number of times the arterial

baroreflex is being active, was a strong independent pre-

dictor of long-term survival among patients with chronic

renal failure, whereas BRS was a predictor of sudden

cardiac death [7].

The data regarding arterial baroreflex function in

patients treated for MDD are scarce and the results have

varied [8, 9]. Electroconvulsive therapy (ECT) is an

effective anti-depressive therapy that is most commonly

reserved for severe treatment resistant depression [10]. No

previous study has assessed baroreflex function among

patients undergoing electro-convulsive therapy in adjunct

to medical therapy for major depressive disorder. We

speculated that arterial baroreflex dysfunction prevails in

severe depressive disease and that the baroreflex dysfunc-

tion would improve after successful therapy.

Methods

The research was carried out in accordance with the Dec-

laration of Helsinki (2000) of the World Medical Associ-

ation and the local ethical committee at Sahlgrenska

University Hospital approved the study and all subjects

gave their informed consent to participate.

Study population

Patients treated for depression

Thirty-three patients with major depressive disorder

according to Diagnostic and Statistical Manual of Mental

Disorders IV criteria who were treated in hospital by ECT

in conjunction to medical anti-depressive treatment were

included in the study. ECT is an effective anti-depressive

therapy that is most commonly reserved for severe treat-

ment resistant depression. Hence, 29 patients were on

anti-depressive drug treatment, a combination of two anti-

depressive drugs were used in five patients and seven

patients were on lithium treatment for the 3 months pre-

ceding the study. Seventeen patients had a history of at

least two previous episodes of major depressive disorder,

whereas eight patients had a bipolar affective disorder.

Exclusion criteria were atrial fibrillation, history of heart

failure, diabetes mellitus, hypertension, renal failure,

myocardial infarction, stroke or medication with drugs

having anticholinergic effects. The average age was

47 years (range 18–81) and there were 27 females. None

had a history of cardiovascular disease or were on treat-

ment with beta receptor blockers, diuretics, calcium

channel blockers, angiotensin converting enzyme inhibitors

or angiotensin II receptor blockers. Thirteen patients were

on treatment with a serotonin and noradrenalin re-uptake

inhibitor (12 on venlafaxin and 1 on duloxetin treatment)

and 12 patients were on treatment with a centrally acting a2

receptor antagonist (11 on mirtazapin and 1 on mianserin

treatment) for the 3 months preceding the baseline inves-

tigations. Anti-depressive medications were not changed

for the 3 months preceding or during the ECT treatments.

At the follow-up examination on average 6 months after

discharge, 9 of 18 patients were on treatment with a

serotonin and noradrenalin re-uptake inhibitor (six on

venlafaxin and three on duloxetin treatment), whereas four

patients were on treatment with centrally acting a2 receptor

antagonist (three on mirtazapin and one on mianserin

treatment). Furthermore, three patients were taking an

antipsychotic agent (two were on risperidon and one on

olanzapin treatment), whereas none were on treatment with

a tricyclic anti-depressive drug. The majority of patients

were on treatment with a sedative or hypnotic drug at

baseline and during the in-hospital treatment. The anti-

depressive drug treatment was continued in the majority of

patients after discharge from hospital.

Healthy subjects

Twenty healthy subjects of similar age and gender distri-

bution as the patients (average age 47 years, range 32–

76 years, 17 females) were recruited by advertisement in a

local newspaper. All healthy subjects were non-smokers,

had no significant past medical history and were not taking

any regular medication. They were all normotensive with

normal ECGs.

Experimental protocol

Patients were included in the study when they were in

hospital for major depressive disorder awaiting ECT

treatment. Beat-to-beat blood pressure and ECG were

recorded continuously during 30 min supine rest on the day

preceding the first ECT, on the day before discharge from

the hospital (on average 18 days, range 3–43 days, after

the first ECT) and at follow up (on average 6 months, range

4–14 months). ECT was administered three times a week

and the total number of treatments varied between 2 and

18, the average value was seven treatments. All 33 patients

were examined at baseline. Of these, 24 underwent follow

up examinations at discharge and 18 were also examined at

follow up 6 months after discharge from hospital.

All patients underwent echocardiography within 3 months

after inclusion in the study.

236 Clin Auton Res (2010) 20:235–240

123

The healthy subjects underwent ECG and continuous

blood pressure monitoring during 20-min rest and answered

the same questionnaires as the patients.

The Montgomery Asberg Depression Rating Scale

(MADRS-S) was used on the investigation days for esti-

mation of the severity of depression. MADRS-S is a vali-

dated nine-item self-rating depression scale developed in

Sweden that has been used in various studies [11, 12]. The

MADRS-S has been validated against the Beck Depression

Inventory as a self-assessment instrument for depression

[11]. Depressive symptoms were classified according to

previous studies as mild (MADRS-S 7-19), moderate

(MADRS-S 20-34) and severe (MADRS-S C35) [13].

Data acquisition and calculations

All subjects refrained from caffeine-containing beverages

for at least 12 h before the investigations. On arrival at the

laboratory, subjects rested supine in a quiet room for

10 min. After the resting period, simultaneous surface ECG

(lead II) and beat-to-beat blood pressure signals measured

by a Portapres device (Finapres Medical Systems,

Amsterdam, The Netherlands) were acquired for 30 min

[14]. Registrations in the current study were recorded at a

sampling frequency of 1,000 Hz and stored on a pc. The

recordings were inspected off-line for removal of artefac-

tual segments and sequences containing non-sinus beats.

The time series of SBP and RR intervals (defined as the

interval between the R-waves of two consecutive heart

beats on the ECG) from the entire recording period were

scanned to identify baroreflex sequences, which were

defined as three or more consecutive beats in which suc-

cessive SBP and RR intervals concordantly increased or

decreased, with the threshold set at 1.0 mmHg and 5.0 ms,

respectively, and a shift of ?1 between the blood pressure

pulse and the RR intervals [15].

Linear regression was applied to each sequence and only

those with the squared correlation coefficient r2 [ 0.85

were accepted for further analysis. The arterial baroreflex

function was estimated by calculating the following (1) the

spontaneous BRS, reflecting the average regression slope

for all the linear regressions plotted for accepted baroreflex

sequences within the whole time frame, (2) the BEI,

defined as the ratio between the number of SBP ramps

followed by the respective reflex PI interval ramps that

fulfilled the BRS criteria and the total number of SBP

ramps was calculated during the recording period accord-

ing to the equation [16]:

BEI ¼ total number of PI=SBP sequences

total number of SBP ramps

For each blood pressure ramp the overall blood pressure

change was calculated and the sloop of the ramp was

estimated by the maximum of the first derivative of the

blood pressure signal within the time interval of the ramp

(max dP/dt). For each blood pressure ramp, the overall

blood pressure change was calculated and the slope of the

ramp was estimated by the maximum of the first derivative

of the blood pressure signal within the time interval of the

ramp (max dP/dt).

A Sequoia C512 ultrasound equipment was used for the

echocardiography examinations. All investigations were

performed by a specialist in cardiology with 15 years

experience of echocardiography. Images were stored on a

hard disk and measurements were performed offline. The

average of three measurements was used. Left ventricular

hypertrophy, systolic and diastolic left ventricular function

were estimated according to guidelines of the American

Society of Echocardiography [17].

Statistics

Numerical distributions are presented by their mean ± SD.

Student’s t test for unpaired and paired comparisons were

used for continuous data with normal distributions. The

BRS and the number of sequences and BEI showed a non-

normal distribution and hence, the Mann–Whitney U test

and Wilcoxon’s sign rank test for unpaired and paired

comparisons were used. For comparisons of depression

scale values, non-parametric tests were used. Comparisons

of proportions were carried out using cross-tabulation and

Fischer’s exact test. Statistical significance was defined as

P \ 0.05.

Results

Patients with major depressive disorder did not differ com-

pared to healthy subjects regarding age, gender distribution,

or body mass index (Table 1). At baseline, systolic blood

pressures and heart rate were elevated among depressive

patients compared to healthy subjects, whereas BRS and BEI

were reduced by 29 and 32%, respectively (P \ 0.01 for all,

Table 1; Fig. 1). The average change of the blood pressure

ramps did not differ between depressive patients and healthy

subjects (5.6 ± 1.7 vs. 5.9 ± 1.4 mmHg for healthy sub-

jects) at baseline. Likewise, the average maximum of the first

derivative of the blood pressure signal within the time

interval of the blood pressure ramps did not differ between

the groups (3.3 ± 1.1 vs. 2.8 ± 0.8 mmHg/s for healthy

subjects).

At discharge from the hospital, on average 18 days

(range 3–43 days) after admission, systolic and diastolic

blood pressures, heart rate, BRS, and BEI were not sig-

nificantly changed (Table 2). Systolic blood pressures and

Clin Auton Res (2010) 20:235–240 237

123

heart rate at discharge remained elevated when compared

with healthy subjects, whereas BRS and BEI were reduced

(P \ 0.05 for all). At the follow-up investigation, on

average 6 months (range 4–14 months) after the baseline

investigation, blood pressures, heart rate, BRS and BEI

remained unchanged when compared with the values

obtained at discharge from the hospital (Table 2).

There were no relationships between BRS or BEI and

the MDRS-S score and patients having MADRS-S score

above the median value of 22 did not differ from other

patients regarding blood pressures, heart rate, BRS, or BEI.

The MADRS-S score decreased after ECT (Table 2,

P \ 0.01 for baseline vs. values at discharge). At discharge

from hospital and at the follow-up examination 73 and

67%, respectively, of the depressive patients had a clini-

cally significant improvement according to MADRS-S

(defined as improvement of at least one depression class,

for example from severe depressive symptoms at baseline

to moderate at discharge). There were no differences

regarding BRS or BEI between patients who improved

after electroconvulsive treatment when compared with

non-responders. The average left ventricular ejection

fraction among depressive patients was 66% (range 55–

78%). None of the patients had a reduced left ventricular

ejection fraction below 50%. Three patients fulfilled the

criteria for left ventricular hypertrophy and three were

classified as having left ventricular diastolic dysfunction.

Discussion

The current study establishes the notion that arterial baro-

reflex dysfunction is prevailing long term in major

depressive disorder. Apart from a reduced gain of the

arterial baroreflex (BRS), an estimation of the number of

times the baroreflex is being active was reduced among

depressive patients. Several studies have demonstrated an

association between reduced BRS and depressive symp-

toms among patients with coronary artery disease, whereas

the results have varied in major depressive disorder

Table 1 Demographical and

measured variables among

patients treated for depressive

illness and healthy subjects at

baseline

a Measured by the Portapres

deviceb Montgomery Asberg

Depression Rating Scale. Pvalues denote statistically

significant difference for values

in patients with depressive

illness versus healthy subjects

Patients with MDD

(n = 33)

Healthy subjects

(n = 20)

P

Age (years, range) 47 (18–81) 49 (33–76) 0.715

Female gender (numbers) 27 17 0.728

Body mass index (kg/m2) 25 ± 4 24 ± 3 0.183

Systolic blood pressure (mmHg)a 128 ± 21 112 ± 9 0.002

Diastolic blood pressure (mmHg)a 64 ± 12 60 ± 10 0.230

Heart rate (bpm) 79 ± 13 62 ± 7 \0.001

Baroreflex sensitivity, BRS (ms/mmHg) 10 ± 7 14 ± 4 0.002

Baroreflex effectiveness index, BEI 0.34 ± 0.20 0.50 ± 0.13 0.001

MADRS-Sb sum (median, range) 33 (12–49) 2 (0-6) \0.001

Fig. 1 Box plots are showing the individual values for BRS (leftpanel) and BEI (right panel) above and below the 90th and below the

10th percentiles, respectively. Boxes are displaying the 75th and 25th

percentiles and lines in boxes represent the median values. Patients

with major depressive disorder (MDD, n = 33) showed reduced

values for BRS and BEI at baseline compared to HS (n = 20,

P \ 0.01 for both)

238 Clin Auton Res (2010) 20:235–240

123

patients without overt cardiovascular disease. Watkins and

co-workers reported that anxiety, but not depression

severity, was associated with reduced BRS in patients with

major depressive disorder [8]. Moreover, a recent study did

not find any differences in BRS between untreated

depressive patients and healthy subjects [18]. On the other

hand, Broadley [9] reported impaired BRS in subjects with

no other cardiac risk factors treated for major depressive

disorder. Interestingly, all patients in the latter study had a

history of two or more episodes of unipolar depression but

were in remission at the time of the study [9]. This cor-

roborates the present findings of BRS remaining reduced

up to 6 months after electroconvulsive treatment when

depressive symptoms have improved. However, although

depressive symptoms improved in the current study, a

majority of patients still reported mild or moderate

depressive symptoms 6 months after the initiation of ECT.

Hence, one may speculate that even mild depressive symp-

toms, which are prevalent among patients with recurrent

depression could impair the arterial baroreflex function

long-term.

The current study demonstrated a reduced BEI among

depressive patients, reflecting a reduced number of times

the arterial baroreflex was being active. Di Rienzo and co-

workers [16] reported that sino-aortic denervation in cats

reduced BEI to a value near zero supporting the contention

that BEI was related to arterial baroreflex function. Even

though the mechanisms behind a reduced BEI remain to be

elucidated, a variable that is closely related to BEI, the

number of baroreflex sequences have been reported to be

reduced in patients with diabetes and a reduced BEI among

chronic renal failure patients was related to diabetes sug-

gesting that neuropathy of the autonomic peripheral nerves

may influence BEI [19, 20]. Neuropathy of the autonomic

peripheral nerves seems less likely in the present popula-

tion of middle-aged depressive patients without diabetes

or overt cardiovascular diseases but central inhibitory

influences affecting the cardiac vagal motor neurons of the

prefrontal cortex and the insular cortex may prevail in

major depressive disorder [21].

Since all the patients were on other anti-depressive

treatments, changes in the outcome variables cannot

strictly be related to ECT treatment alone. Another limi-

tation of the current study is the possibility of a drug effect

on the arterial baroreflex function. Anti-depressive medi-

cation in severe major depressive disorder is commonly

used long-term, sometimes for several years after recur-

rences. We did not observe any differences regarding BRS

or BEI between patients on drugs increasing central nor-

adrenergic transmission and other patients. Likewise,

Broadley and co-workers [9 reported similar values for

BRS in patients on and off treatment with drugs increasing

the central noradrenergic transmission, whereas Garakani

and co-workers 22] reported reduced heart rate variability

in depressive patients on sertraline treatment in conjunction

to cognitive behavioral therapy compared to patients who

were only treated by cognitive behavioral therapy.

The present data cannot establish the clinical impact of

arterial baroreflex dysfunction in major depressive disor-

der. However, reduced BRS has been linked to sudden

death and hence, the current observations may explain

some of the increased risk for sudden death reported in

major depressive disorders [4, 5]. Previous studies using

medical treatment alone or in adjunct to cognitive behav-

iour therapy in depression have failed to decrease the

incidence of cardiovascular diseases or improve survival

although the patients were relieved from depressive

symptoms [23]. There are experimental data supporting the

notion of a protective effect against ventricular arrhythmias

and sudden death by an intact BRS [24]. During a reha-

bilitation programme after myocardial infarction, patients

who responded to training by increasing BRS had a more

favourable outcome compared to patients who failed to

improve BRS [25]. One may speculate that physical exercise

Table 2 Measured variables are displayed for patients with major depressive disorder who underwent investigations at baseline before elec-

troconvulsive therapy, at discharge from hospital and 6 months after discharge

Baseline (n = 18) At dischargea (n = 18) Follow upb (n = 18)

Systolic blood pressure (mmHg) 126 ± 19 120 ± 20 119 ± 26

Diastolic blood pressure (mmHg) 64 ± 13 58 ± 13 61 ± 17

Heart rate (beats per minute) 78 ± 11 80 ± 8 78 ± 9

Baroreflex Sensitivity, BRS (ms/mmHg) 9 ± 5 8 ± 3 10 ± 6

Baroreflex effectiveness Index (BEI) 0.37 ± 0.18 0.38 ± 0.23 0.36 ± 0.15

MADRS-Sc sum (median, range) 32 (17–46) 16 (2–30)** 14 (0–37)**

** Denotes a statistically significant difference versus baseline, P \ 0.01a The average duration of the hospital stay was 18 days (range 3–43 days)b Follow up investigation was performed on average 6 months (range 4–14 months) after the baseline investigationc Montgomery Asberg Depression Rating Scale

Clin Auton Res (2010) 20:235–240 239

123

programs, which may improve both depressive symptoms

and the arterial baroreflex function could reduce the risk of

sudden cardiac death and improve survival in major depres-

sive disorders.

Acknowledgments We gratefully acknowledge Gun Bodehed-Berg

and Ruth Jonsson (members of the staff) for assistance with data

acquisition. This work was supported by grants from the Scientific

Council of Halland.

References

1. Barefoot JC, Schroll M (1996) Symptoms of depression, acute

myocardial infarction, and total mortality in a community sample

[see comments]. Circulation 93:1976–1980

2. Broadley AJ, Korszun A, Jones CJ, Frenneaux MP (2002) Arte-

rial endothelial function is impaired in treated depression. Heart

88:521–523

3. Ford DE, Erlinger TP (2004) Depression and C-reactive protein

in US adults: data from the Third National Health and Nutrition

Examination Survey. Arch Intern Med 164:1010–1014

4. Luukinen H, Laippala P, Huikuri HV (2003) Depressive symp-

toms and the risk of sudden cardiac death among the elderly. Eur

Heart J 24:2021–2026

5. Empana JP, Jouven X, Lemaitre RN, Sotoodehnia N, Rea T,

Raghunathan TE, Simon G, Siscovick DS (2006) Clinical

depression and risk of out-of-hospital cardiac arrest. Arch Intern

Med 166:195–200

6. La Rovere MT, Bigger JT Jr, Marcus FI, Mortara A, Schwartz PJ

(1998) Baroreflex sensitivity and heart-rate variability in pre-

diction of total cardiac mortality after myocardial infarction.

ATRAMI (autonomic tone and reflexes after myocardial infarc-

tion) Investigators [see comments]. Lancet 351:478–484

7. Johansson M, Gao SA, Friberg P, Annerstedt M, Carlstrom J,

Ivarsson T, Jensen G, Ljungman S, Mathillas O, Nielsen FD,

Strombom U (2007) Baroreflex effectiveness index and baro-

reflex sensitivity predict all-cause mortality and sudden death in

hypertensive patients with chronic renal failure. J Hypertens

25:163–168

8. Watkins LL, Grossman P, Krishnan R, Blumenthal JA (1999)

Anxiety reduces baroreflex cardiac control in older adults with

major depression [see comments]. Psychosom Med 61:334–340

9. Broadley AJ, Frenneaux MP, Moskvina V, Jones CJ, Korszun A

(2005) Baroreflex sensitivity is reduced in depression. Psychosom

Med 67:648–651

10. Khalid N, Atkins M, Tredget J, Giles M, Champney-Smith K,

Kirov G (2008) The effectiveness of electroconvulsive therapy

in treatment-resistant depression: a naturalistic study. J ECT

24:141–145

11. Svanborg P, Asberg M (2001) A comparison between the Beck

Depression Inventory (BDI) and the self-rating version of the

montgomery asberg depression rating scale (MADRS). J Affect

Disord 64:203–216

12. Montgomery SA, Asberg M (1979) A new depression scale

designed to be sensitive to change. Br J Psychiatry 134:382–389

13. Herrmann N, Black SE, Lawrence J, Szekely C, Szalai JP (1998)

The sunnybrook stroke study: a prospective study of depressive

symptoms and functional outcome. Stroke 29:618–624

14. Imholz BP, Langewouters GJ, van Montfrans GA, Parati G, van

Goudoever J, Wesseling KH, Wieling W, Mancia G (1993)

Feasibility of ambulatory, continuous 24-h finger arterial pressure

recording. Hypertension 21:65–73

15. Gao SA, Johansson M, Rundqvist B, Lambert G, Jensen G,

Friberg P (2002) Reduced spontaneous baroreceptor sensitivity in

patients with renovascular hypertension. J Hypertens 20:111–116

16. Di Rienzo M, Parati G, Castiglioni P, Tordi R, Mancia G, Pedotti

A (2001) Baroreflex effectiveness index: an additional measure of

baroreflex control of heart rate in daily life. Am J Physiol Regul

Integr Comp Physiol 280:R744–R751

17. Cheitlin MD, Armstrong WF, Aurigemma GP, Beller GA, Bier-

man FZ, Davis JL, Douglas PS, Faxon DP, Gillam LD, Kimball

TR, Kussmaul WG, Pearlman AS, Philbrick JT, Rakowski H,

Thys DM (2003) ACC/AHA/ASE 2003 guideline update for the

clinical application of echocardiography––summary article: a

report of the American College of Cardiology/American Heart

Association Task Force on practice guidelines (ACC/AHA/ASE

Committee to update the 1997 guidelines for the clinical appli-

cation of echocardiography). J Am Coll Cardiol 42:954–970

18. Dawood T, Lambert EA, Barton DA, Laude D, Elghozi JL, Esler

MD, Haikerwal D, Kaye DM, Hotchkin EJ, Lambert GW (2007)

Specific serotonin reuptake inhibition in major depressive disor-

der adversely affects novel markers of cardiac risk. Hypertens

Res 30:285–293

19. Frattola A, Parati G, Gamba P, Paleari F, Mauri G, Di Rienzo M,

Castiglioni P, Mancia G (1997) Time and frequency domain

estimates of spontaneous baroreflex sensitivity provide early

detection of autonomic dysfunction in diabetes mellitus. Dia-

betologia 40:1470–1475

20. Johansson M, Gao SA, Friberg P, Annerstedt M, Bergstrom G,

Carlstrom J, Ivarsson T, Jensen G, Ljungman S, Mathillas O,

Nielsen FD, Strombom U (2005) Reduced baroreflex effective-

ness index in hypertensive patients with chronic renal failure. Am

J Hypertens 18:995–1000

21. Verberne AJ, Owens NC (1998) Cortical modulation of the

cardiovascular system. Prog Neurobiol 54:149–168

22. Garakani A, Martinez JM, Aaronson CJ, Voustianiouk A, Kauf-

mann H, Gorman JM (2009) Effect of medication and psycho-

therapy on heart rate variability in panic disorder. Depress

Anxiety 26:251–258

23. Berkman LF, Blumenthal J, Burg M, Carney RM, Catellier D,

Cowan MJ, Czajkowski SM, De Busk R, Hosking J, Jaffe A,

Kaufmann PG, Mitchell P, Norman J, Powell LH, Raczynski JM,

Schneiderman N (2003) Effects of treating depression and low

perceived social support on clinical events after myocardial

infarction: the enhancing recovery in coronary heart disease

patients (ENRICHD) randomized trial. JAMA 289:3106–3116

24. Schwartz PJ, Vanoli E, Stramba-Badiale M, De Ferrari GM,

Billman GE, Foreman RD (1988) Autonomic mechanisms and

sudden death. New insights from analysis of baroreceptor reflexes

in conscious dogs with and without a myocardial infarction.

Circulation 78:969–979

25. La Rovere MT, Bersano C, Gnemmi M, Specchia G, Schwartz PJ

(2002) Exercise-induced increase in baroreflex sensitivity pre-

dicts improved prognosis after myocardial infarction. Circulation

106:945–959

240 Clin Auton Res (2010) 20:235–240

123