Hostname: page-component-cd9895bd7-gbm5v Total loading time: 0 Render date: 2024-12-27T11:45:16.969Z Has data issue: false hasContentIssue false
  • English
  • Français

Attenuated vagally-mediated heart rate variability at rest and in response to postural maneuvers in patients with generalized anxiety disorder

Published online by Cambridge University Press:  07 June 2019

Hsin-An Chang ,
Wen-Hui Fang ,
Fang-Jung Wan ,
Nian-Sheng Tzeng ,
Yia-Ping Liu ,
Jia-Fwu Shyu ,
Tieh-Ching Chang ,
San-Yuan Huang  and
Chuan-Chia Chang Open the ORCID record for Chuan-Chia Chang [Opens in a new window]
Hsin-An Chang
Affiliation:
Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
Wen-Hui Fang
Affiliation:
Department of Family and Community Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
Fang-Jung Wan
Affiliation:
Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
Nian-Sheng Tzeng
Affiliation:
Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
Yia-Ping Liu
Affiliation:
Department of Psychiatry, Cheng Hsin General Hospital, Taipei, Taiwan Departments of Physiology and Psychiatry, Laboratory of Cognitive Neuroscience, National Defense Medical Center, Taipei, Taiwan
Jia-Fwu Shyu
Affiliation:
Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan
Tieh-Ching Chang
Affiliation:
Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
San-Yuan Huang
Affiliation:
Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
Chuan-Chia Chang*
Affiliation:
Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
*
Author for correspondence: Chuan-Chia Chang, E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Altered heart rate variability (HRV), an index of autonomic nervous system function, has been reported in generalized anxiety disorder (GAD), but the results have been mixed. Thus, the present study, using a large sample size and better methodology, aims to examine whether GAD is associated with impaired HRV, both at rest and in response to posture challenges.

Methods

In total, 1832 participants were recruited in this study, consisting of 682 patients with GAD (including 326 drug- and comorbidity-free GAD patients) and 1150 healthy controls. Short-term HRV was measured during the supine-standing-supine test (5-min per position). Propensity score matching (PSM), a relatively novel method, was used to control for potential confounders.

Results

After PSM algorithm, drug- and comorbidity-free GAD patients had reductions in resting (baseline) high-frequency power (HF), an index for parasympathetic modulation, and increases in the low-frequency/HF ratio (LF/HF), an index for sympathovagal balance as compared to matched controls. Furthermore, the responses of HF and LF/HF to posture changes were all attenuated when compared with matched controls. Effect sizes, given by Cohen's d, for resting HF and HF reactivity were 0.42 and 0.36–0.42, respectively.

Conclusions

GAD is associated with altered sympathovagal balance, characterized by attenuation in both resting vagal modulation and vagal reactivity, with an almost medium effect size (Cohen's d ≈ 0.4), regardless of medication use or comorbidity status.

Keywords

Autonomic dysregulationgeneralized anxiety disorderheart rate variabilityresting vagal modulationsupine-standing-supine testvagal reactivity
Type
Original Articles
Information
Psychological Medicine , Volume 50 , Issue 9 , July 2020 , pp. 1433 - 1441
Copyright
Copyright © Cambridge University Press 2019

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

*

Equal contributors.

References

Alvares, GA, Quintana, DS, Hickie, IB and Guastella, AJ (2016) Autonomic nervous system dysfunction in psychiatric disorders and the impact of psychotropic medications: a systematic review and meta-analysis. The Journal of Psychiatry & Neuroscience 41, 89–104.CrossRefGoogle ScholarPubMed
Chalmers, JA, Quintana, DS, Abbott, MJ and Kemp, AH (2014) Anxiety disorders are associated with reduced heart rate variability: a meta-analysis. Frontiers in Psychiatry 5, 80.CrossRefGoogle ScholarPubMed
Chang, HA, Chang, CC, Tzeng, NS, Kuo, TB, Lu, RB and Huang, SY (2013 a) Cardiac autonomic dysregulation in acute schizophrenia. Acta Neuropsychiatrica 25, 155–164.CrossRefGoogle ScholarPubMed
Chang, HA, Chang, CC, Tzeng, NS, Kuo, TB, Lu, RB and Huang, SY (2013 b) Generalized anxiety disorder, comorbid major depression and heart rate variability: a case-control study in Taiwan. Psychiatry Investigation 10, 326–335.CrossRefGoogle ScholarPubMed
Chen, HY (2000) Guidebook of Beck Depression Inventory-II-Chinese Version. Taipei, Taiwan: Chinese Behavioral Science Corporation.Google Scholar
Diamond, AE and Fisher, AJ (2016) Comparative autonomic responses to diagnostic interviewing between individuals with GAD, MDD, SAD and healthy controls. Frontiers in Human Neuroscience 10, 677.Google ScholarPubMed
Faul, F, Erdfelder, E, Buchner, A and Lang, AG (2009) Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behavior Research Methods 41, 1149–1160.CrossRefGoogle ScholarPubMed
Fisher, AJ and Newman, MG (2013) Heart rate and autonomic response to stress after experimental induction of worry versus relaxation in healthy, high-worry, and generalized anxiety disorder individuals. Biological Psychology 93, 65–74.CrossRefGoogle ScholarPubMed
Frasure-Smith, N and Lesperance, F (2008) Depression and anxiety as predictors of 2-year cardiac events in patients with stable coronary artery disease. Archives of General Psychiatry 65, 62–71.CrossRefGoogle ScholarPubMed
Galuszka, J, Opavsky, J, Lukl, J, Stejskal, P, Zapletalova, J and Salinger, J (2004) Short-term spectral analysis of heart rate variability during supine-standing-supine test in patients with paroxysmal atrial fibrillation. Biomedical Papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia 148, 63–67.CrossRefGoogle ScholarPubMed
Greaves-Lord, K, Tulen, J, Dietrich, A, Sondeijker, F, van Roon, A, Oldehinkel, A, Ormel, J, Verhulst, F and Huizink, A (2010) Reduced autonomic flexibility as a predictor for future anxiety in girls from the general population: the TRAILS study. Psychiatry Research 179, 187–193.CrossRefGoogle ScholarPubMed
Hammel, JC, Smitherman, TA, McGlynn, FD, Mulfinger, AM, Lazarte, AA and Gothard, KD (2011) Vagal influence during worry and cognitive challenge. Anxiety, Stress, and Coping 24, 121–136.CrossRefGoogle ScholarPubMed
Hansen, BB and Bowers, J (2008) Covariate balance in simple, stratified and clustered comparative studies. Statistical Science 23, 219–236.CrossRefGoogle Scholar
Jetty, PV, Charney, DS and Goddard, AW (2001) Neurobiology of generalized anxiety disorder. The Psychiatric Clinics of North America 24, 75–97.CrossRefGoogle ScholarPubMed
Jiang, XL, Zhang, ZG, Ye, CP, Lei, Y, Wu, L, Zhang, Y, Chen, YY and Xiao, ZJ (2015) Attenuated or absent HRV response to postural change in subjects with primary insomnia. Physiology & Behavior 140, 127–131.CrossRefGoogle ScholarPubMed
Kemp, AH, Brunoni, AR, Santos, IS, Nunes, MA, Dantas, EM, Carvalho de Figueiredo, R, Pereira, AC, Ribeiro, AL, Mill, JG, Andreao, RV, Thayer, JF, Bensenor, IM and Lotufo, PA (2014) Effects of depression, anxiety, comorbidity, and antidepressants on resting-state heart rate and its variability: an ELSA-Brasil cohort baseline study. The American Journal of Psychiatry 171, 1328–1334.CrossRefGoogle ScholarPubMed
Kessler, RC, Gruber, M, Hettema, JM, Hwang, I, Sampson, N and Yonkers, KA (2008) Co-morbid major depression and generalized anxiety disorders in the National Comorbidity Survey follow-up. Psychological Medicine 38, 365–374.CrossRefGoogle ScholarPubMed
Kingwell, BA, Thompson, JM, Kaye, DM, McPherson, GA, Jennings, GL and Esler, MD (1994) Heart rate spectral analysis, cardiac norepinephrine spillover, and muscle sympathetic nerve activity during human sympathetic nervous activation and failure. Circulation 90, 234–240.CrossRefGoogle ScholarPubMed
Kogan, AV, Allen, JJ and Weihs, KL (2012) Cardiac vagal control as a prospective predictor of anxiety in women diagnosed with breast cancer. Biological Psychology 90, 105–111.CrossRefGoogle ScholarPubMed
Levine, JC, Fleming, R, Piedmont, JI, Cain, SM and Chen, WJ (2016) Heart rate variability and generalized anxiety disorder during laboratory-induced worry and aversive imagery. Journal of Affective Disorders 205, 207–215.CrossRefGoogle ScholarPubMed
Licht, CM, de Geus, EJ, van Dyck, R and Penninx, BW (2009) Association between anxiety disorders and heart rate variability in The Netherlands Study of Depression and Anxiety (NESDA). Psychosomatic Medicine 71, 508–518.CrossRefGoogle Scholar
Lin, YJ (2000) Manual for the Beck Anxiety Inventory. Taipei, Taiwan: Chinese Behavioral Science Corporation.Google Scholar
Lyonfields, JD, Borkovec, TD and Thayer, JF (1995) Vagal tone in generalized anxiety disorder and the effects of aversive imagery and worrisome thinking. Behavior Therapy 26, 457–466.CrossRefGoogle Scholar
Martens, EJ, de Jonge, P, Na, B, Cohen, BE, Lett, H and Whooley, MA (2010) Scared to death? Generalized anxiety disorder and cardiovascular events in patients with stable coronary heart disease: The Heart and Soul Study. Archives of General Psychiatry 67, 750–758.CrossRefGoogle ScholarPubMed
McCaffrey, DF, Griffin, BA, Almirall, D, Slaughter, ME, Ramchand, R and Burgette, LF (2013) A tutorial on propensity score estimation for multiple treatments using generalized boosted models. Statistics in Medicine 32, 3388–3414.CrossRefGoogle ScholarPubMed
Noyes, R Jr (2001) Comorbidity in generalized anxiety disorder. The Psychiatric Clinics of North America 24, 41–55.CrossRefGoogle ScholarPubMed
Pittig, A, Arch, JJ, Lam, CW and Craske, MG (2013) Heart rate and heart rate variability in panic, social anxiety, obsessive-compulsive, and generalized anxiety disorders at baseline and in response to relaxation and hyperventilation. International Journal of Psychophysiology 87, 19–27.CrossRefGoogle ScholarPubMed
Pradeep, J, Sambashivaiah, S, Thomas, T, Radhakrishnan, R, Vaz, M and Srinivasan, K (2012) Heart rate variability responses to standing are attenuated in drug naive depressed patients. Indian Journal of Physiology and Pharmacology 56, 213–221.Google ScholarPubMed
Quintana, DS, Elstad, M, Kaufmann, T, Brandt, CL, Haatveit, B, Haram, M, Nerhus, M, Westlye, LT and Andreassen, OA (2016) Resting-state high-frequency heart rate variability is related to respiratory frequency in individuals with severe mental illness but not healthy controls. Scientific Reports 6, 37212.CrossRefGoogle Scholar
Reyes del Paso, GA, Langewitz, W, Mulder, LJ, van Roon, A and Duschek, S (2013) The utility of low frequency heart rate variability as an index of sympathetic cardiac tone: a review with emphasis on a reanalysis of previous studies. Psychophysiology 50, 477–487.CrossRefGoogle ScholarPubMed
Sheehan, DV, Lecrubier, Y, Sheehan, KH, Amorim, P, Janavs, J, Weiller, E, Hergueta, T, Baker, R and Dunbar, GC (1998) The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. The Journal of Clinical Psychiatry 59, 22–33.Google ScholarPubMed
Shinba, T (2017) Major depressive disorder and generalized anxiety disorder show different autonomic dysregulations revealed by heart-rate variability analysis in first-onset drug-naive patients without comorbidity. Psychiatry and Clinical Neurosciences 71, 135–145.CrossRefGoogle ScholarPubMed
Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology (1996) Heart rate variability: standards of measurement, physiological interpretation and clinical use. Circulation 93, 1043–1065.CrossRefGoogle Scholar
Thayer, JF and Lane, RD (2007) The role of vagal function in the risk for cardiovascular disease and mortality. Biological Psychology 74, 224–242.CrossRefGoogle ScholarPubMed
Thayer, JF, Friedman, BH and Borkovec, TD (1996) Autonomic characteristics of generalized anxiety disorder and worry. Biological Psychiatry 39, 255–266.CrossRefGoogle ScholarPubMed
Thoemmes, F (2012) Propensity score matching in SPSS. Available at http://arxiv.org/ftp/arxiv/papers/1201/1201.6385.pdf.Google Scholar
Tonhajzerova, I, Ondrejka, I, Javorka, K, Turianikova, Z, Farsky, I and Javorka, M (2010) Cardiac autonomic regulation is impaired in girls with major depression. Progress in Neuro-Psychopharmacology & Biological Psychiatry 34, 613–618.CrossRefGoogle ScholarPubMed
Tu, YK, Gunnell, D and Gilthorpe, MS (2008) Simpson's Paradox, Lord's Paradox, and Suppression Effects are the same phenomenon – the reversal paradox. Emerging Themes in Epidemiology 5, 2.CrossRefGoogle ScholarPubMed
Tully, PJ, Cosh, SM and Baune, BT (2013) A review of the affects of worry and generalized anxiety disorder upon cardiovascular health and coronary heart disease. Psychology, Health & Medicine 18, 627–644.CrossRefGoogle ScholarPubMed
Tully, PJ, Winefield, HR, Baker, RA, Denollet, J, Pedersen, SS, Wittert, GA and Turnbull, DA (2015) Depression, anxiety and major adverse cardiovascular and cerebrovascular events in patients following coronary artery bypass graft surgery: a five year longitudinal cohort study. BioPsychoSocial Medicine 9, 14.CrossRefGoogle ScholarPubMed