The physiological effects of slow breathing in the healthy human

Marc A Russo, Danielle M Santarelli, Dean O'Rourke, Marc A Russo, Danielle M Santarelli, Dean O'Rourke

Abstract

Slow breathing practices have been adopted in the modern world across the globe due to their claimed health benefits. This has piqued the interest of researchers and clinicians who have initiated investigations into the physiological (and psychological) effects of slow breathing techniques and attempted to uncover the underlying mechanisms. The aim of this article is to provide a comprehensive overview of normal respiratory physiology and the documented physiological effects of slow breathing techniques according to research in healthy humans. The review focuses on the physiological implications to the respiratory, cardiovascular, cardiorespiratory and autonomic nervous systems, with particular focus on diaphragm activity, ventilation efficiency, haemodynamics, heart rate variability, cardiorespiratory coupling, respiratory sinus arrhythmia and sympathovagal balance. The review ends with a brief discussion of the potential clinical implications of slow breathing techniques. This is a topic that warrants further research, understanding and discussion.

Key points: Slow breathing practices have gained popularity in the western world due to their claimed health benefits, yet remain relatively untouched by the medical community.Investigations into the physiological effects of slow breathing have uncovered significant effects on the respiratory, cardiovascular, cardiorespiratory and autonomic nervous systems.Key findings include effects on respiratory muscle activity, ventilation efficiency, chemoreflex and baroreflex sensitivity, heart rate variability, blood flow dynamics, respiratory sinus arrhythmia, cardiorespiratory coupling, and sympathovagal balance.There appears to be potential for use of controlled slow breathing techniques as a means of optimising physiological parameters that appear to be associated with health and longevity, and that may extend to disease states; however, there is a dire need for further research into the area.

Educational aims: To provide a comprehensive overview of normal human respiratory physiology and the documented effects of slow breathing in healthy humans.To review and discuss the evidence and hypotheses regarding the mechanisms underlying slow breathing physiological effects in humans.To provide a definition of slow breathing and what may constitute "autonomically optimised respiration".To open discussion on the potential clinical implications of slow breathing techniques and the need for further research.

Conflict of interest statement

Conflict of interest None declared.

Figures

Figure 1
Figure 1
Maximum HRV is typically observed at about a respiratory frequency of 6 breaths per min (0.1 Hz). Reproduced from [25] with permission from the publisher.
Figure 2
Figure 2
Simplified model of cardiorespiratory control showing coupling between respiratory and cardiovascular systems. τ: circulatory delay; ILV: instantaneous lung volume; HR: heart rate; CNS: central nervous system; SAP: systolic arterial pressure; DAP: diastolic arterial pressure. Reproduced from [108] with permission from the publisher.

References

    1. Jerath R, Edry JW, Barnes VA, et al. Physiology of long pranayamic breathing: neural respiratory elements may provide a mechanism that explains how slow deep breathing shifts the autonomic nervous system. Med Hypotheses 2006; 67: 566–571.
    1. Brown RP, Gerbarg PL. Sudarshan Kriya yogic breathing in the treatment of stress, anxiety, and depression: part I-neurophysiologic model. J Altern Complement Med 2005; 11: 189–201.
    1. Bruton A, Lewith GT. The Buteyko breathing technique for asthma: a review. Complement Ther Med 2005; 13: 41–46.
    1. Courtney R. The functions of breathing and its dysfunctions and their relationship to breathing therapy. Int J Osteopath Med 2009; 12: 78–85.
    1. Prem V, Sahoo RC, Adhikari P. Comparison of the effects of Buteyko and pranayama breathing techniques on quality of life in patients with asthma – a randomized controlled trial. Clin Rehabil 2013; 27: 133–141.
    1. Macedo TM, Freitas DA, Chaves GS, et al. Breathing exercises for children with asthma. Cochrane Database Syst Rev 2016; 4: CD011017.
    1. Freitas DA, Holloway EA, Bruno SS, et al. Breathing exercises for adults with asthma. Cochrane Database Syst Rev 2013: CD001277.
    1. Cowie RL, Conley DP, Underwood MF, et al. A randomised controlled trial of the Buteyko technique as an adjunct to conventional management of asthma. Respir Med 2008; 102: 726–732.
    1. Cooper S, Oborne J, Newton S, et al. Effect of two breathing exercises (Buteyko and pranayama) in asthma: a randomised controlled trial. Thorax 2003; 58: 674–679.
    1. Burgess J, Ekanayake B, Lowe A, et al. Systematic review of the effectiveness of breathing retraining in asthma management. Expert Rev Respir Med 2011; 5: 789–807.
    1. Downey R. Anatomy of the normal diaphragm. Thorac Surg Clin 2011; 21: 273–279, ix.
    1. Cluzel P, Similowski T, Chartrand-Lefebvre C, et al. Diaphragm and chest wall: assessment of the inspiratory pump with MR imaging-preliminary observations. Radiology 2000; 215: 574–583.
    1. De Troyer A, Wilson TA. Action of the diaphragm on the rib cage. J Appl Physiol 2016; 121: 391–400.
    1. Brochard L. Transdiaphragmatic Pressure In: Benito S, Net A, eds. Pulmonary Function in Mechanically Ventilated Patients. Berlin, Springer Berlin Heidelberg, 1991; pp. 52–61.
    1. De Troyer A, Boriek AM. Mechanics of the respiratory muscles. Compr Physiol 2011; 1: 1273–1300.
    1. Vostatek P, Novak D, Rychnovsky T, et al. Diaphragm postural function analysis using magnetic resonance imaging. PloS One 2013; 8: e56724.
    1. Kolar P, Neuwirth J, Sanda J, et al. Analysis of diaphragm movement during tidal breathing and during its activation while breath holding using MRI synchronized with spirometry. Physiol Res 2009; 58: 383–392.
    1. Stromberg SE, Russell ME, Carlson CR. Diaphragmatic breathing and its effectiveness for the management of motion sickness. Aerosp Med Hum Perform 2015; 86: 452–457.
    1. Nattie E, Li A. Central chemoreceptors: locations and functions. Compr Physiol 2012; 2: 221–254.
    1. Paterson DJ, Nye PC. Reflexes arising from the arterial chemoreceptors. Adv Exp Med Biol 1994; 360: 71–86.
    1. Bernardi L, Gabutti A, Porta C, et al. Slow breathing reduces chemoreflex response to hypoxia and hypercapnia, and increases baroreflex sensitivity. J Hypertens 2001; 19: 2221–2229.
    1. Braun SR. Respiratory Rate and Pattern In: Walker HK, Hall WD, Hurst JW, eds. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd Edn. Boston, Butterworth-Heinemann Ltd, 1990.
    1. Bilo G, Revera M, Bussotti M, et al. Effects of slow deep breathing at high altitude on oxygen saturation, pulmonary and systemic hemodynamics. PloS one 2012; 7: e49074.
    1. Bernardi L, Spadacini G, Bellwon J, et al. Effect of breathing rate on oxygen saturation and exercise performance in chronic heart failure. Lancet 1998; 351: 1308–1311.
    1. Bernardi L, Porta C, Gabutti A, et al. Modulatory effects of respiration. Auton Neurosci 2001; 90: 47–56.
    1. Wise RA, Robotham JL, Summer WR. Effects of spontaneous ventilation on the circulation. Lung 1981; 159: 175–186.
    1. Shekerdemian L, Bohn D. Cardiovascular effects of mechanical ventilation. Arch Dis Child 1999; 80: 475–480.
    1. Toska K, Eriksen M. Respiration-synchronous fluctuations in stroke volume, heart rate and arterial pressure in humans. J Physiol (Lond) 1993; 472: 501–512.
    1. Hsieh CW, Mao CW, Young MS, et al. Respiratory effect on the pulse spectrum. J Med Eng Technol 2003; 27: 77–84.
    1. Dick TE, Mims JR, Hsieh YH, et al. Increased cardio-respiratory coupling evoked by slow deep breathing can persist in normal humans. Respir Physiol Neurobiol 2014; 204: 99–111.
    1. Bordoni B, Zanier E. Anatomic connections of the diaphragm: influence of respiration on the body system. J Multidiscip Healthc 2013; 6: 281–291.
    1. Byeon K, Choi JO, Yang JH, et al. The response of the vena cava to abdominal breathing. J Altern Complement Med 2012; 18: 153–157.
    1. Kimura BJ, Dalugdugan R, Gilcrease GW, et al. The effect of breathing manner on inferior vena caval diameter. Eur J Echocardiogr 2011; 12: 120–123.
    1. Ovadia-Blechman Z, Gavish B, Levy-Aharoni D, et al. The coupling between peripheral microcirculation and slow breathing. Med Eng Phys 2017; 39: 49–56.
    1. Elstad M. Respiratory variations in pulmonary and systemic blood flow in healthy humans. Acta Physiol (Oxf) 2012; 205: 341–348.
    1. Laude D, Goldman M, Escourrou P, et al. Effect of breathing pattern on blood pressure and heart rate oscillations in humans. Clin Exp Pharmacol Physiol 1993; 20: 619–626.
    1. Feihl F, Broccard AF. Interactions between respiration and systemic hemodynamics. Part I: basic concepts. Intensive Care Med 2009; 35: 45–54.
    1. Billman GE. Heart rate variability – a historical perspective. Front Physiol 2011; 2: 86.
    1. Eckberg DL. The human respiratory gate. J Physiol (Lond) 2003; 548: 339–352.
    1. Dick TE, Hsieh YH, Dhingra RR, et al. Cardiorespiratory coupling: common rhythms in cardiac, sympathetic, and respiratory activities. Prog Brain Res 2014; 209: 191–205.
    1. Radaelli A, Raco R, Perfetti P, et al. Effects of slow, controlled breathing on baroreceptor control of heart rate and blood pressure in healthy men. J Hypertens 2004; 22: 1361–1370.
    1. Chang Q, Liu R, Shen Z. Effects of slow breathing rate on blood pressure and heart rate variabilities. Int J Cardiol 2013; 169: e6–e8.
    1. Zhang Z, Wang B, Wu H, et al. Effects of slow and regular breathing exercise on cardiopulmonary coupling and blood pressure. Med Biol Eng Comput 2016; 55: 327–341.
    1. Joseph CN, Porta C, Casucci G, et al. Slow breathing improves arterial baroreflex sensitivity and decreases blood pressure in essential hypertension. Hypertension 2005; 46: 714–718.
    1. Hayano J, Yasuma F, Okada A, et al. Respiratory sinus arrhythmia. A phenomenon improving pulmonary gas exchange and circulatory efficiency. Circulation 1996; 94: 842–847.
    1. Lopes TC, Beda A, Granja-Filho PC, et al. Cardio-respiratory interactions and relocation of heartbeats within the respiratory cycle during spontaneous and paced breathing. Physiol Meas 2011; 32: 1389–1401.
    1. Lorenzi-Filho G, Dajani HR, Leung RS, et al. Entrainment of blood pressure and heart rate oscillations by periodic breathing. Am J Respir Crit Care Med 1999; 159: 1147–1154.
    1. Mortola JP, Marghescu D, Siegrist-Johnstone R. Thinking about breathing: Effects on respiratory sinus arrhythmia. Respir Physiol Neurobiol 2016; 223: 28–36.
    1. Malliani A, Lombardi F, Pagani M. Power spectrum analysis of heart rate variability: a tool to explore neural regulatory mechanisms. Br Heart J 1994; 71: 1–2.
    1. Parati G, Saul JP, Di Rienzo M, et al. Spectral analysis of blood pressure and heart rate variability in evaluating cardiovascular regulation. A critical appraisal. Hypertension 1995; 25: 1276–1286.
    1. Sleight P, La Rovere MT, Mortara A, et al. Physiology and pathophysiology of heart rate and blood pressure variability in humans: is power spectral analysis largely an index of baroreflex gain? Clin Sci 1995; 88: 103–109.
    1. Badra LJ, Cooke WH, Hoag JB, et al. Respiratory modulation of human autonomic rhythms. Am J Physiol Heart Circ Physiol 2001; 280: H2674–H2688.
    1. Wehrwein EA, Joyner MJ. Regulation of blood pressure by the arterial baroreflex and autonomic nervous system. Handb Clin Neurol 2013; 117: 89–102.
    1. Cohen MA, Taylor JA. Short-term cardiovascular oscillations in man: measuring and modelling the physiologies. J Physiol (Lond) 2002; 542: 669–683.
    1. Julien C. The enigma of Mayer waves: facts and models. Cardiovasc Res 2006; 70: 12–21.
    1. Akselrod S, Gordon D, Madwed JB, et al. Hemodynamic regulation: investigation by spectral analysis. Am J Physiol 1985; 249: H867–H875.
    1. Baselli G, Porta A, Cerutti S, et al. RR-arterial pressure variability relationships. Auton Neurosci 2001; 90: 57–65.
    1. Cevese A, Gulli G, Polati E, et al. Baroreflex and oscillation of heart period at 0.1 Hz studied by alpha-blockade and cross-spectral analysis in healthy humans. J Physiol (Lond) 2001; 531: 235–244.
    1. Lanfranchi PA, Somers VK. Arterial baroreflex function and cardiovascular variability: interactions and implications. Am J Physiol Regul Integr Comp Physiol 2002; 283: R815–R826.
    1. Pitzalis MV, Mastropasqua F, Massari F, et al. Effect of respiratory rate on the relationships between RR interval and systolic blood pressure fluctuations: a frequency-dependent phenomenon. Cardiovasc Res 1998; 38: 332–339.
    1. Guzik P, Piskorski J, Krauze T, et al. Correlations between the Poincare plot and conventional heart rate variability parameters assessed during paced breathing. J Physiol Sci 2007; 57: 63–71.
    1. Sin PY, Galletly DC, Tzeng YC. Influence of breathing frequency on the pattern of respiratory sinus arrhythmia and blood pressure: old questions revisited. Am J Physiol Heart Circ Physiol 2010; 298: H1588–H1599.
    1. Tharion E, Samuel P, Rajalakshmi R, et al. Influence of deep breathing exercise on spontaneous respiratory rate and heart rate variability: a randomised controlled trial in healthy subjects. Indian J Physiol Pharmacol 2012; 56: 80–87.
    1. Paprika D, Gingl Z, Rudas L, et al. Hemodynamic effects of slow breathing: does the pattern matter beyond the rate? Acta Physiol Hung 2014; 101: 273–281.
    1. Brown TE, Beightol LA, Koh J, et al. Important influence of respiration on human R-R interval power spectra is largely ignored. J Appl Physiol 1993; 75: 2310–2317.
    1. Beda A, Simpson DM, Carvalho NC, et al. Low-frequency heart rate variability is related to the breath-to-breath variability in the respiratory pattern. Psychophysiology 2014; 51: 197–205.
    1. Wang YP, Kuo TB, Lai CT, et al. Effects of respiratory time ratio on heart rate variability and spontaneous baroreflex sensitivity. J Appl Physiol 2013; 115: 1648–1655.
    1. Wang YP, Kuo TB, Lai CT, et al. Effects of breathing frequency on baroreflex effectiveness index and spontaneous baroreflex sensitivity derived by sequence analysis. J Hypertens 2012; 30: 2151–2158.
    1. Lin IM, Tai LY, Fan SY. Breathing at a rate of 5.5 breaths per minute with equal inhalation-to-exhalation ratio increases heart rate variability. Int J Psychophysiol 2014; 91: 206–211.
    1. Berntson GG, Cacioppo JT, Quigley KS. Respiratory sinus arrhythmia: autonomic origins, physiological mechanisms, and psychophysiological implications. Psychophysiology 1993; 30: 183–196.
    1. Yasuma F, Hayano J. Respiratory sinus arrhythmia: why does the heartbeat synchronize with respiratory rhythm? Chest 2004; 125: 683–690.
    1. Angelone A, Coulter NA Jr. Respiratory sinus arrhythmia: a frequency dependent phenomenon. J Appl Physiol 1964; 19: 479–482.
    1. Hirsch JA, Bishop B. Respiratory sinus arrhythmia in humans: how breathing pattern modulates heart rate. Am J Physiol 1981; 241: H620–H629.
    1. Ben-Tal A, Shamailov SS, Paton JF. Central regulation of heart rate and the appearance of respiratory sinus arrhythmia: new insights from mathematical modeling. Math Biosci 2014; 255: 71–82.
    1. Vaschillo EG, Vaschillo B, Lehrer PM. Characteristics of resonance in heart rate variability stimulated by biofeedback. Appl Psychophysiol Biofeedback 2006; 31: 129–142.
    1. Taylor JA, Myers CW, Halliwill JR, et al. Sympathetic restraint of respiratory sinus arrhythmia: implications for vagal-cardiac tone assessment in humans. Am J Physiol Heart Circ Physiol 2001; 280: H2804–H2814.
    1. Eckberg DL, Kifle YT, Roberts VL. Phase relationship between normal human respiration and baroreflex responsiveness. J Physiol (Lond) 1980; 304: 489–502.
    1. Giardino ND, Glenny RW, Borson S, et al. Respiratory sinus arrhythmia is associated with efficiency of pulmonary gas exchange in healthy humans. Am J Physiol Heart Circ Physiol 2003; 284: H1585–H1591.
    1. Ito S, Sasano H, Sasano N, et al. Vagal nerve activity contributes to improve the efficiency of pulmonary gas exchange in hypoxic humans. Exp Physiol 2006; 91: 935–941.
    1. Hayano J, Yasuma F. Hypothesis: respiratory sinus arrhythmia is an intrinsic resting function of cardiopulmonary system. Cardiovasc Res 2003; 58: 1–9.
    1. Ben-Tal A, Shamailov SS, Paton JF. Evaluating the physiological significance of respiratory sinus arrhythmia: looking beyond ventilation-perfusion efficiency. J Physiol (Lond) 2012; 590: 1989–2008.
    1. Larsen PD, Tzeng YC, Sin PY, et al. Respiratory sinus arrhythmia in conscious humans during spontaneous respiration. Respir Physiol Neurobiol 2010; 174: 111–118.
    1. Grossman P, Kollai M. Respiratory sinus arrhythmia, cardiac vagal tone, and respiration: within- and between-individual relations. Psychophysiology 1993; 30: 486–495.
    1. Piepoli M, Sleight P, Leuzzi S, et al. Origin of respiratory sinus arrhythmia in conscious humans. An important role for arterial carotid baroreceptors. Circulation 1997; 95: 1813–1821.
    1. deBoer RW, Karemaker JM, Strackee J. Hemodynamic fluctuations and baroreflex sensitivity in humans: a beat-to-beat model. Am J Physiol 1987; 253: H680–H689.
    1. Baselli G, Cerutti S, Badilini F, et al. Model for the assessment of heart period and arterial pressure variability interactions and of respiration influences. Med Biol Eng Comput 1994; 32: 143–152.
    1. Tafil-Klawe M, Trzebski A, Klawe J. Contribution of the carotid chemoreceptor reflex to the mechanism of respiratory sinus arrhythmia in young healthy and hypertensive humans. Acta Physiol Pol 1985; 36: 59–64.
    1. Crystal GJ, Salem MR. The Bainbridge and the “reverse” Bainbridge reflexes: history, physiology, and clinical relevance. Anesth Analg 2012; 114: 520–532.
    1. Stauss HM. Heart rate variability. Am J Physiol Regul Integr Comp Physiol 2003; 285: R927–R931.
    1. Taha BH, Simon PM, Dempsey JA, et al. Respiratory sinus arrhythmia in humans: an obligatory role for vagal feedback from the lungs. J Appl Physiol 1995; 78: 638–645.
    1. Kapidzic A, Platisa MM, Bojic T, et al. RR interval-respiratory signal waveform modeling in human slow paced and spontaneous breathing. Respir Physiol Neurobiol 2014; 203: 51–59.
    1. Spyer KM. Central nervous mechanisms responsible for cardio-respiratory homeostasis. Adv Exp Med Biol 1995; 381: 73–79.
    1. Lopes OU, Palmer JF. Proposed respiratory ‘gating’ mechanism for cardiac slowing. Nature 1976; 264: 454–456.
    1. Coote JH, Chauhan RA. The sympathetic innervation of the heart: Important new insights. Auton Neurosci 2016; 199: 17–23.
    1. Elghozi JL, Julien C. Sympathetic control of short-term heart rate variability and its pharmacological modulation. Fundam Clin Pharmacol 2007; 21: 337–347.
    1. Koizumi K, Terui N, Kollai M. Effect of cardiac vagal and sympathetic nerve activity on heart rate in rhythmic fluctuations. J Auton Nerv Syst 1985; 12: 251–259.
    1. Jalife J, Slenter VA, Salata JJ, et al. Dynamic vagal control of pacemaker activity in the mammalian sinoatrial node. Circ Res 1983; 52: 642–656.
    1. Mendelowitz D. Advances in Parasympathetic Control of Heart Rate and Cardiac Function. News Physiol Sci 1999; 14: 155–161.
    1. Pomeranz B, Macaulay RJ, Caudill MA, et al. Assessment of autonomic function in humans by heart rate spectral analysis. Am J Physiol 1985; 248: H151–H153.
    1. Malliani A, Pagani M, Lombardi F, et al. Cardiovascular neural regulation explored in the frequency domain. Circulation 1991; 84: 482–492.
    1. Pagani M, Lombardi F, Guzzetti S, et al. Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog. Circ Res 1986; 59: 178–193.
    1. Akselrod S, Gordon D, Ubel FA, et al. Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science 1981; 213: 220–222.
    1. Zhang PZ, Tapp WN, Reisman SS, et al. Respiration response curve analysis of heart rate variability. IEEE Trans Biomed Eng 1997; 44: 321–325.
    1. Seals DR, Suwarno NO, Dempsey JA. Influence of lung volume on sympathetic nerve discharge in normal humans. Circ Res 1990; 67: 130–141.
    1. Pal GK, Velkumary S, Madanmohan. Effect of short-term practice of breathing exercises on autonomic functions in normal human volunteers. Indian J Med Res 2004; 120: 115–121.
    1. Limberg JK, Morgan BJ, Schrage WG, et al. Respiratory influences on muscle sympathetic nerve activity and vascular conductance in the steady state. Am J Physiol Heart Circ Physiol 2013; 304: H1615–H1623.
    1. Vidigal GA, Tavares BS, Garner DM, et al. Slow breathing influences cardiac autonomic responses to postural maneuver: Slow breathing and HRV. Complement Ther Clin Pract 2016; 23: 14–20.
    1. Pinna GD, Maestri R, Mortara A, et al. Cardiorespiratory interactions during periodic breathing in awake chronic heart failure patients. Am J Physiol Heart Circ Physiol 2000; 278: H932–H941.
    1. Lundberg JO, Settergren G, Gelinder S, et al. Inhalation of nasally derived nitric oxide modulates pulmonary function in humans. Acta Physiol Scand 1996; 158: 343–347.
    1. Stauss HM, Persson PB. Role of Nitric Oxide in Buffering Short-Term Blood Pressure Fluctuations. News Physiol Sci 2000; 15: 229–233.
    1. Tsuji H, Larson MG, Venditti FJ Jr, et al. Impact of reduced heart rate variability on risk for cardiac events. The Framingham Heart Study. Circulation 1996; 94: 2850–2855.
    1. Nolan J, Batin PD, Andrews R, et al. Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-heart). Circulation 1998; 98: 1510–1516.
    1. La Rovere MT, Pinna GD, Hohnloser SH, et al. Baroreflex sensitivity and heart rate variability in the identification of patients at risk for life-threatening arrhythmias: implications for clinical trials. Circulation 2001; 103: 2072–2077.
    1. Aeschbacher S, Schoen T, Dorig L, et al. Heart rate, heart rate variability and inflammatory biomarkers among young and healthy adults. Ann Med 2016: 1–26.
    1. Aeschbacher S, Bossard M, Ruperti Repilado FJ, et al. Healthy lifestyle and heart rate variability in young adults. Eur J Prev Cardiol 2016; 23: 1037–1044.
    1. Buccelletti E, Gilardi E, Scaini E, et al. Heart rate variability and myocardial infarction: systematic literature review and metanalysis. Eur Rev Med Pharmacol Sci 2009; 13: 299–307.
    1. Zulfiqar U, Jurivich DA, Gao W, et al. Relation of high heart rate variability to healthy longevity. Am J Cardiol 2010; 105: 1181–1185.
    1. 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.
    1. Thayer JF, Lane RD. The role of vagal function in the risk for cardiovascular disease and mortality. Biol Psychol 2007; 74: 224–242.

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