0
Get Alert
Please Wait... Processing your request... Please Wait.
You must sign in to sign-up for alerts.

Please confirm that your email address is correct, so you can successfully receive this alert.

Article   |    
Effects of Depression, Anxiety, Comorbidity, and Antidepressants on Resting-State Heart Rate and Its Variability: An ELSA-Brasil Cohort Baseline Study
Andrew H. Kemp, Ph.D.; Andre R. Brunoni, M.D., Ph.D.; Itamar S. Santos, M.D., Ph.D.; Maria A. Nunes, M.D., Ph.D.; Eduardo M. Dantas, Ph.D.; Roberta Carvalho de Figueiredo, Ph.D.; Alexandre C. Pereira, M.D., Ph.D.; Antonio L.P. Ribeiro, M.D., Ph.D.; José G. Mill, M.D., Ph.D.; Rodrigo V. Andreão, Ph.D.; Julian F. Thayer, Ph.D.; Isabela M. Benseñor, M.D., Ph.D.; Paulo A. Lotufo, M.D., Dr.P.H.
Am J Psychiatry 2014;:. doi:10.1176/appi.ajp.2014.13121605
View Author and Article Information

The authors report no financial relationships with commercial interests.

Dr. Kemp is supported by an International Research Professorship from the University of São Paulo, Brazil. Dr. Ribeiro is supported by a research grant (Pesquisador Mineiro) from the Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), the research agency of the state of Minas Gerais, Brazil. Dr. Brunoni is a recipient of a young investigator award from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), the research agency of the state of São Paulo, Brazil. The ELSA-Brasil baseline study was supported by the Brazilian Ministry of Health (Science and Technology Department) and the Brazilian Ministry of Science and Technology (Financiadora de Estudos e Projetos and Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq, the national research council of Brazil) (grants 01 06 0010.00 RS, 01 06 0212.00 BA, 01 06 0300.00 ES, 01 06 0278.00 MG, 01 06 0115.00 SP, 01 06 0071.00 RJ). Drs. Kemp and Bensenor are recipients of funding from FAPESP and Ohio State University (2013/50327-6).

From University Hospital and the Faculty of Medicine, University of São Paulo, São Paulo, Brazil; the School of Psychology and Discipline of Psychiatry, University of Sydney, Sydney, Australia; the Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Brazil; the Collegiate of Biological Sciences, Federal University of Vale do São Francisco, Petrolina, Pernambuco, Brazil; Campus Centro Oeste Dona Lindu, Federal University of São João Del-Rei, Brazil; the Laboratory of Genetics and Molecular Cardiology, Heart Institute/InCor, University of São Paulo Medical School, São Paulo; Hospital das Clínicas and Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil; the Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, Brazil; and the Department of Psychology, Ohio State University, Columbus.

Presented in part at the annual meeting of the American Heart Association, Dallas, Nov. 16–20, 2013.

Address correspondence to Dr. Kemp (andrew.kemp@hu.usp.br or andrew.kemp@sydney.edu.au).

Copyright © 2014 by the American Psychiatric Association

Received December 09, 2013; Revised March 27, 2014; Revised May 29, 2014; Accepted June 16, 2014.

Abstract

Objective  Increases in resting-state heart rate and decreases in its variability are associated with substantial morbidity and mortality, yet contradictory findings have been reported for the effects of the mood and anxiety disorders and of antidepressants. The authors investigated heart rate and heart rate variability in a large cohort from Brazil, using propensity score weighting, a relatively novel method, to control for numerous potential confounders.

Method  A total of 15,105 participants were recruited in the Brazilian Longitudinal Study of Adult Health. Mood and anxiety disorders were ascertained using the Portuguese version of the Clinical Interview Schedule–Revised. Heart rate and its variability were extracted from 10-minute resting-state electrocardiograms. Regressions weighted by propensity scores were carried out to compare participants with and without depressive or anxiety disorders, as well as users and non-users of antidepressants, on heart rate and heart rate variability.

Results  Use of antidepressants was associated with increases in heart rate and decreases in its variability. Effects were most pronounced for the tricyclic antidepressants (Cohen’s d, 0.72–0.81), followed by serotonin and norepinephrine reuptake inhibitors (Cohen’s d, 0.42–0.95) and other antidepressants (Cohen’s d, 0.37–0.40), relative to participants not on antidepressants. Only participants with generalized anxiety disorder showed robust, though small, increases in heart rate and decreases in its variability after propensity score weighting.

Conclusions  The findings may, in part, underpin epidemiological findings of increased risk for cardiovascular morbidity and mortality. Many factors that have an adverse impact on cardiac activity were controlled for in this study, highlighting the importance of cardiovascular risk reduction strategies. Further study is needed to examine whether, how, and when such effects contribute to morbidity and mortality.

Abstract Teaser
Figures in this Article

Your Session has timed out. Please sign back in to continue.
Sign In Your Session has timed out. Please sign back in to continue.
Sign In to Access Full Content
 
Username
Password
Sign in via Athens (What is this?)
Athens is a service for single sign-on which enables access to all of an institution's subscriptions on- or off-site.
Not a subscriber?

Subscribe Now/Learn More

PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.

Need more help? PsychiatryOnline Customer Service may be reached by emailing PsychiatryOnline@psych.org or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).

FIGURE 1. Key Findings Associated With the Impact of Antidepressants on Heart Rate and Its Variability After Propensity Score Weightinga

a lnRMSSD=log-transformed root mean square of successive difference; lnHF=log-transformed high-frequency component; SSRI=selective serotonin reuptake inhibitor; SNRI=serotonin and norepinephrine reuptake inhibitor. Error bars indicate 95% confidence intervals corresponding to the propensity score weighted regression. Antidepressant group sizes are follows: no antidepressant, N=14,069; SSRI, N=356; SNRI, N=52; tricyclic antidepressant, N=84; other antidepressant, N=75.

+

References

Thayer  JF;  Hansen  AL;  Saus-Rose  E;  Johnsen  BH:  Heart rate variability, prefrontal neural function, and cognitive performance: the neurovisceral integration perspective on self-regulation, adaptation, and health.  Ann Behav Med 2009; 37:141–153
[CrossRef] | [PubMed]
 
Porges  SW:  The Polyvagal Theory: Neurophysiological Foundations of Emotions, Attachment, Communication, and Self-Regulation .  New York,  WW Norton, 2011
 
Saul  JP:  Beat-to-beat variations of heart rate reflect modulation of cardiac autonomic outflow.  Physiology (Bethesda) 1990; 5:32–37
 
Kemp  AH;  Quintana  DS:  The relationship between mental and physical health: insights from the study of heart rate variability.  Int J Psychophysiol 2013; 89:288–296
[CrossRef] | [PubMed]
 
Kleiger  RE;  Miller  JP;  Bigger  JT  Jr;  Moss  AJ:  Decreased heart rate variability and its association with increased mortality after acute myocardial infarction.  Am J Cardiol 1987; 59:256–262
[CrossRef] | [PubMed]
 
Carney  RM;  Rich  MW;  teVelde  A;  Saini  J;  Clark  K;  Freedland  KE:  The relationship between heart rate, heart rate variability, and depression in patients with coronary artery disease.  J Psychosom Res 1988; 32:159–164
[CrossRef] | [PubMed]
 
Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology:  Heart rate variability: standards of measurement, physiological interpretation, and clinical use.  Circulation 1996; 93:1043–1065
[CrossRef] | [PubMed]
 
Thayer  JF;  Friedman  BH;  Borkovec  TD:  Autonomic characteristics of generalized anxiety disorder and worry.  Biol Psychiatry 1996; 39:255–266
[CrossRef] | [PubMed]
 
Kemp  AH;  Quintana  DS;  Felmingham  KL;  Matthews  S;  Jelinek  HF:  Depression, comorbid anxiety disorders, and heart rate variability in physically healthy, unmedicated patients: implications for cardiovascular risk.  PLoS One 2012; 7:e30777
[CrossRef] | [PubMed]
 
Licht  CMM;  de Geus  EJC;  van Dyck  R;  Penninx  BWJH:  Longitudinal evidence for unfavorable effects of antidepressants on heart rate variability.  Biol Psychiatry 2010; 68:861–868
[CrossRef] | [PubMed]
 
Licht  CMM;  Penninx  BWJH;  de Geus  EJC:  Effects of antidepressants, but not psychopathology, on cardiac sympathetic control: a longitudinal study.  Neuropschopharmacology , 2012, 37:2487–2495
[CrossRef]
 
Tu  Y-K;  Gunnell  D;  Gilthorpe  MS:  Simpson’s paradox, Lord’s paradox, and suppression effects are the same phenomenon: the reversal paradox.  Emerg Themes Epidemiol 2008; 5:2
[CrossRef] | [PubMed]
 
McCaffrey  DF;  Griffin  BA;  Almirall  D;  Slaughter  ME;  Ramchand  R;  Burgette  LF:  A tutorial on propensity score estimation for multiple treatments using generalized boosted models.  Stat Med 2013; 32:3388–3414
[CrossRef] | [PubMed]
 
Ridgeway  G:  Assessing the effect of race bias in post-traffic stop outcomes using propensity scores.  J Quant Criminol 2006; 22:1–29
[CrossRef]
 
Schmidt  MI;  Duncan  BB;  Mill  JG;  Lotufo  PA;  Chor  D;  Barreto  SM;  Aquino  EM;  Passos  VMA;  Matos  SM;  Molina  MDCB;  Carvalho  MS;  Benseñor  IM:  Cohort profile: Longitudinal Study of Adult Health (ELSA-Brasil).  Int J Epidemiol  (Epub ahead of print, Feb 27, 2014)
 
Kemp  AH;  Quintana  DS;  Gray  MA;  Felmingham  KL;  Brown  K;  Gatt  JM:  Impact of depression and antidepressant treatment on heart rate variability: a review and meta-analysis.  Biol Psychiatry 2010; 67:1067–1074
[CrossRef] | [PubMed]
 
Brunoni  AR;  Kemp  AH;  Dantas  EM;  Goulart  AC;  Nunes  MA;  Boggio  PS;  Mill  JG;  Lotufo  PA;  Fregni  F;  Benseñor  IM:  Heart rate variability is a trait marker of major depressive disorder: evidence from the Sertraline vs Electric Current Therapy to Treat Depression Clinical Study.  Int J Neuropsychopharmacol 2013; 16:1937–1949
[CrossRef] | [PubMed]
 
Nunes  MA;  de Mello Alves  MG;  Chor  D;  Schmidt  MI;  Duncan  BB:  Adaptação transcultural do CIS-R (Clinical Interview Schedule–Revised Version) para o português no Estudo Longitudinal de Saúde do Adulto (ELSA).  Revista HCPA 2012; 31:487–490
 
Lewis  G;  Pelosi  AJ;  Araya  R;  Dunn  G:  Measuring psychiatric disorder in the community: a standardized assessment for use by lay interviewers.  Psychol Med 1992; 22:465–486
[CrossRef] | [PubMed]
 
Dantas  EM;  Sant’Anna  ML;  Andreão  RV;  Gonçalves  CP;  Morra  EA;  Baldo  MP;  Rodrigues  SL;  Mill  JG:  Spectral analysis of heart rate variability with the autoregressive method: what model order to choose? Comput Biol Med 2012; 42:164–170
[CrossRef] | [PubMed]
 
Nemeroff  CB;  Goldschmidt-Clermont  PJ:  Heartache and heartbreak: the link between depression and cardiovascular disease.  Nat Rev Cardiol 2012; 9:526–539
[CrossRef] | [PubMed]
 
Moffitt  TE;  Harrington  H;  Caspi  A;  Kim-Cohen  J;  Goldberg  D;  Gregory  AM;  Poulton  R:  Depression and generalized anxiety disorder: cumulative and sequential comorbidity in a birth cohort followed prospectively to age 32 years.  Arch Gen Psychiatry 2007; 64:651–660
[CrossRef] | [PubMed]
 
Rottenberg  J:  Cardiac vagal control in depression: a critical analysis.  Biol Psychol 2007; 74:200–211
[CrossRef] | [PubMed]
 
Licht  CMM;  de Geus  EJC;  Zitman  FG;  Hoogendijk  WJG;  van Dyck  R;  Penninx  BWJH:  Association between major depressive disorder and heart rate variability in the Netherlands Study of Depression and Anxiety (NESDA).  Arch Gen Psychiatry 2008; 65:1358–1367
[CrossRef] | [PubMed]
 
Licht  CMM;  de Geus  EJC;  van Dyck  R;  Penninx  BWJH:  Association between anxiety disorders and heart rate variability in the Netherlands Study of Depression and Anxiety (NESDA).  Psychosom Med 2009; 71:508–518
[CrossRef] | [PubMed]
 
Ioannidis  JPA:  Why most discovered true associations are inflated.  Epidemiology 2008; 19:640–648
[CrossRef] | [PubMed]
 
Koole  SL;  Lakens  D:  Rewarding replications: a sure and simple way to improve psychological science.  Perspect Psychol Sci 2012; 7:608–614
[CrossRef]
 
Alvares  GA;  Quintana  DS;  Kemp  AH;  Van Zwieten  A;  Balleine  BW;  Hickie  IB;  Guastella  AJ:  Reduced heart rate variability in social anxiety disorder: associations with gender and symptom severity.  PLoS ONE 2013; 8:e70468
[CrossRef] | [PubMed]
 
Whang  W;  Kubzansky  LD;  Kawachi  I;  Rexrode  KM;  Kroenke  CH;  Glynn  RJ;  Garan  H;  Albert  CM:  Depression and risk of sudden cardiac death and coronary heart disease in women: results from the Nurses’ Health Study.  J Am Coll Cardiol 2009; 53:950–958
[CrossRef] | [PubMed]
 
Hamer  M;  Batty  GD;  Seldenrijk  A;  Kivimaki  M:  Antidepressant medication use and future risk of cardiovascular disease: the Scottish Health Survey.  Eur Heart J 2011; 32:437–442
[CrossRef] | [PubMed]
 
Fox  K;  Borer  JS;  Camm  AJ;  Danchin  N;  Ferrari  R;  Lopez Sendon  JL;  Steg  PG;  Tardif  J-C;  Tavazzi  L;  Tendera  M; Heart Rate Working Group:  Resting heart rate in cardiovascular disease.  J Am Coll Cardiol 2007; 50:823–830
[CrossRef] | [PubMed]
 
Hanson  CS;  Outhred  T;  Brunoni  AR;  Malhi  GS;  Kemp  AH:  The impact of escitalopram on vagally mediated cardiovascular function to stress and the moderating effects of vigorous physical activity: a randomized controlled treatment study in healthy participants.  Front Physiol 2013; 4:259
[PubMed]
 
Sandercock  GRH;  Bromley  PD;  Brodie  DA:  The reliability of short-term measurements of heart rate variability.  Int J Cardiol 2005; 103:238–247
[CrossRef] | [PubMed]
 
Dantas  EM;  Gonçalves  CP;  Silva  ABT;  Rodrigues  SL;  Ramos  MS;  Andreão  RV;  Pimentel  EB;  Lunz  W;  Mill  JG:  Reproducibility of heart rate variability parameters measured in healthy subjects at rest and after a postural change maneuver.  Braz J Med Biol Res 2010; 43:982–988
[CrossRef] | [PubMed]
 
Penttilä  J;  Helminen  A;  Jartti  T;  Kuusela  T;  Huikuri  HV;  Tulppo  MP;  Coffeng  R;  Scheinin  H:  Time domain, geometrical and frequency domain analysis of cardiac vagal outflow: effects of various respiratory patterns.  Clin Physiol 2001; 21:365–376
[CrossRef] | [PubMed]
 
References Container
+
+

CME Activity

There is currently no quiz available for this resource. Please click here to go to the CME page to find another.
Submit a Comments
Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discertion of APA editorial staff.

* = Required Field
(if multiple authors, separate names by comma)
Example: John Doe



Related Content
Articles
Books
Textbook of Traumatic Brain Injury, 2nd Edition > Chapter 35.  >
Manual of Clinical Psychopharmacology, 7th Edition > Chapter 12.  >
Dulcan's Textbook of Child and Adolescent Psychiatry > Chapter 50.  >
Manual of Clinical Psychopharmacology, 7th Edition > Chapter 12.  >
The American Psychiatric Publishing Textbook of Geriatric Psychiatry, 4th Edition > Chapter 26.  >
Topic Collections
Psychiatric News
APA Guidelines
PubMed Articles