Sympathetic Neural and Adrenal Medullary Mechanisms in Depression and Panic Disorder

  • Murray EslerEmail author


The pathway towards the current recognition1 - 3 that mental stress and psychiatric ­illness is a cause of cardiovascular disease has been long, halting and at times vigorously defended by opposing forces of the medical status quo. For many years this claimed relation of acute mental stress to heart attacks was largely based on individual anecdotes, such as the celebrated case of the famous eighteenth-century English ­surgeon, John Hunter, who wrote that he was at the mercy of any scoundrel who aggravated him, then proved the point by dying suddenly in the middle of a stormy meeting of the board of his hospital.


Sympathetic nervous system Adrenal medullary mechanisms Depression Panic disorder Psychoneurocardiology Adrenaline secretion Sympathetic pathophysiology 


  1. 1.
    Rozanski A, Blumenthal JA, Kaplan J. Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy. Circulation. 1999;99:2192-2217.PubMedCrossRefGoogle Scholar
  2. 2.
    Bunker SJ, Colquhoun DM, Esler MD, et al. “Stress” and coronary heart disease: psychosocial risk factors. National Heart Foundation of Australia position statement update. Med J Aust. 2003;178:272-276.PubMedGoogle Scholar
  3. 3.
    Esler M, Schwarz R, Alvarenga M. Mental stress is a cause of cardiovascular diseases: from skepticism to certainty. Stress Health. 2008;24:175-180.CrossRefGoogle Scholar
  4. 4.
    Leor J, Poole WK, Kloner RA. Sudden cardiac death triggered by an earthquake. N Engl J Med. 1996;334:413-419.PubMedCrossRefGoogle Scholar
  5. 5.
    Hagbarth K-E, Vallbo AB. Pulse and respiratory grouping of sympathetic impulses in human muscle nerves. Acta Physiol Scand. 1968;74:96-106.PubMedCrossRefGoogle Scholar
  6. 6.
    Lambert E, Straznicky N, Schlaich MP, et al. Differing patterns of sympathoexcitation in ­normal weight and obesity-related hypertension. Hypertension. 2007;50:862-868.PubMedCrossRefGoogle Scholar
  7. 7.
    Esler M, Jennings G, Korner P, et al. Measurement of total and organ-specific norepinephrine kinetics in humans. Am J Physiol. 1984;247:E21-E28. Endocrinol Metab 10.PubMedGoogle Scholar
  8. 8.
    Esler M, Jennings G, Lambert G, et al. Overflow of catecholamine neurotransmitters to the circulation: source, fate and functions. Physiol Rev. 1990;70:963-985.PubMedGoogle Scholar
  9. 9.
    Macefield V, Wallin BG, Vallbo AB. The discharge behaviour of single vasoconstrictor motoneurones in human muscle nerves. J Physiol. 1994;481:799-809.PubMedGoogle Scholar
  10. 10.
    Barton DA, Dawood T, Lambert EA, et al. Sympathetic activity in major depressive disorder: identifying those at increased cardiac risk? J Hypertens. 2007;25:2117-2124.PubMedCrossRefGoogle Scholar
  11. 11.
    Wilkinson DJC, Thompson JM, Lambert GW, et al. Sympathetic activity in patients with panic disorder at rest, under laboratory mental stress and during panic attacks. Arch Gen Psychiatry. 1998;55:511-520.PubMedCrossRefGoogle Scholar
  12. 12.
    Eisenhofer G, Friberg P, Rundqvist B, et al. Cardiac sympathetic nerve function in congestive heart failure. Circulation. 1996;93:1667-1676.PubMedCrossRefGoogle Scholar
  13. 13.
    Alvarenga ME, Richards JC, Lambert G, et al. Psychophysiological mechanisms in panic ­disorder: a correlative analysis of noradrenaline spillover, neuronal noradrenaline reuptake, power spectral analysis of heart rate variability and psychological variables. Psychosom Med. 2006;68:8-12.PubMedCrossRefGoogle Scholar
  14. 14.
    Esler M, Alvarenga M, Lambert G, et al. Cardiac sympathetic nerve biology and brain ­monoamine turnover in panic disorder. Ann N Y Acad Sci. 2004;1018:505-514.PubMedCrossRefGoogle Scholar
  15. 15.
    Esler M, Eikelis N, Schlaich M, et al. Human sympathetic nerve biology: parallel influences of stress and epigenetics in essential hypertension and panic disorder. Ann N Y Acad Sci. 2008;1148:338-348.PubMedCrossRefGoogle Scholar
  16. 16.
    Mansour VM, Wilkinson DJC, Jennings GL, et al. Panic disorder: coronary spasm as a basis for cardiac risk? Med J Aust. 1998;168:390-392.PubMedGoogle Scholar
  17. 17.
    Kawachi I, Colditz GA, Ascherio A, et al. Prospective study of phobic anxiety and risk of ­coronary heart disease in men. Circulation. 1994;89:1992-1997.PubMedCrossRefGoogle Scholar
  18. 18.
    Kawachi I, Sparrow D, Vokanas PS, et al. Symptoms of anxiety and coronary heart disease. The Normative Aging Study. Circulation. 1994;90:2225-2229.PubMedCrossRefGoogle Scholar
  19. 19.
    Albert CM, Chae CU, Rexrode KM, et al. Phobic anxiety and risk of coronary heart disease and sudden cardiac death among women. Circulation. 2005;111:480-487.PubMedCrossRefGoogle Scholar
  20. 20.
    Lambert E, Hotchkin E, Alvarenga M, et al. Single-unit analysis of sympathetic nervous ­discharges in patients with panic disorder. J Physiol. 2006;570:637-643.PubMedCrossRefGoogle Scholar
  21. 21.
    Lambert E, Dawood T, Schlaich M, et al. Single-unit sympathetic discharge pattern in pathological conditions associated with elevated cardiovascular risk. Clin Exp Pharmacol Physiol. 2008;35:503-507.PubMedCrossRefGoogle Scholar
  22. 22.
    Esler M, Eikelis N, Schlaich M, et al. Chronic mental stress is a cause of essential hypertension: presence of biological markers of stress. Clin Exp Pharmacol Physiol. 2008;35:498-502.PubMedCrossRefGoogle Scholar
  23. 23.
    Lambert E, Dawood T, Straznicky N, et al. Association between the sympathetic firing pattern and anxiety level in patients with the metabolic syndrome and elevated blood pressure. J Hypertens. 2010;28(3):543-550.PubMedCrossRefGoogle Scholar
  24. 24.
    Micutkova L, Krepsova K, Sabban E, et al. Modulation of catecholamine-synthesizing enzymes in the rat heart by repeated immobilization stress. Ann N Y Acad Sci. 2004;1018:424-429.PubMedCrossRefGoogle Scholar
  25. 25.
    Rumantir MS, Kaye DM, Jennings GL, et al. Phenotypic evidence of faulty neuronal ­noradrenaline reuptake in essential hypertension. Hypertension. 2000;36:824-829.PubMedCrossRefGoogle Scholar
  26. 26.
    Esler M, Wallin G, Dorward P, et al. Effects of desipramine on sympathetic nerve firing and norepinephrine spillover to plasma in man. Am J Physiol. 1991;260:R817-R823.PubMedGoogle Scholar
  27. 27.
    Esler M, Alvarenga M, Pier C, et al. The neuronal noradrenaline transporter, anxiety and ­cardiovascular disease. J Psychopharmacol. 2006;20(suppl):60-66.PubMedCrossRefGoogle Scholar
  28. 28.
    Hass M. Neuropeptide Y: a cardiac sympathetic cotransmitter? In: Goldstein DS, McCarthy R, eds. Catecholamines: Bridging Basic Science with Clinical Medicine. New York: Academic; 1998:129-132.Google Scholar
  29. 29.
    Wilbert-Lampen U, Leistner D, Greven S, et al. Cardiovascular events during World Cup ­soccer. N Engl J Med. 2008;358:475-483.PubMedCrossRefGoogle Scholar
  30. 30.
    Frasure-Smith N, Lesperance F, Talajiic M. Depression following myocardial infarction: impact on 6-month survival. JAMA. 1993;270:1819-1861.PubMedCrossRefGoogle Scholar
  31. 31.
    Anda R, Williamson D, Jones D, et al. Depressed affect, hopelessness, and the risk of ischemic heart disease in a cohort of U.S. adults. Epidemiology. 1993;4:285-294.PubMedCrossRefGoogle Scholar
  32. 32.
    Musselman DL, Evans DL, Nemeroff CB. The relationship of depression to cardiovascular disease. Arch Gen Psychiatry. 1998;55:580-592.PubMedCrossRefGoogle Scholar
  33. 33.
    Esler M, Turbott J, Schwarz R, et al. The peripheral kinetics of norepinephrine in depressive illness. Arch Gen Psychiatry. 1982;9:295-300.CrossRefGoogle Scholar
  34. 34.
    Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2008;29:2388-2442.PubMedCrossRefGoogle Scholar
  35. 35.
    Scalco AZ, Rondon MUPB, Trombetta IC, et al. Muscle sympathetic nervous activity in depressed patients before and after treatment with sertraline. J Hypertens. 2009;27:2429-2436.PubMedCrossRefGoogle Scholar
  36. 36.
    Esler M, Lambert E, Alvarenga M, et al. Increased brain serotonin turnover in panic disorder patients in the absence of a panic attack: reduction by a selective serotonin reuptake inhibitor. Stress. 2007;10:295-304.PubMedCrossRefGoogle Scholar
  37. 37.
    Barton DA, Esler MD, Dawood T, et al. Elevated brain serotonin turnover in patients with depression: effect of genotype and therapy. Arch Gen Psychiatry. 2008;65:1-9.Google Scholar
  38. 38.
    Meredith IT, Broughton A, Jennings GL, et al. Evidence for a selective increase in resting cardiac sympathetic activity in some patients suffering sustained out of hospital ventricular arrhythmias. N Engl J Med. 1991;325:618-624.PubMedCrossRefGoogle Scholar
  39. 39.
    Kaye DM, Lefkovits J, Jennings GL, et al. Adverse consequences of high sympathetic nervous activity in the failing human heart. J Am Coll Cardiol. 1995;26:1257-1263.PubMedCrossRefGoogle Scholar
  40. 40.
    Brunner-La Rocca HP, Esler MD, Jennings GL, et al. Effect of cardiac sympathetic nervous activity on mode of death in congestive heart failure. Eur Heart J. 2001;22:1136-1143.PubMedCrossRefGoogle Scholar
  41. 41.
    Zipes DP. The long QT interval syndrome. A Rosetta stone for sympathetic related ventricular tachyarrhythmias. Circulation. 1991;84:1414-1419.PubMedCrossRefGoogle Scholar
  42. 42.
    Zoccali C, Mallamaci F, Parlongo S, et al. Plasma norepinephrine predicts survival and incident cardiovascular events in patients with end-stage renal disease. Circulation. 2002;105:1354-1359.PubMedCrossRefGoogle Scholar
  43. 43.
    Esler M, Jennings G, Lambert G. Measurement of overall and cardiac norepinephrine release into plasma during cognitive challenge. Psychoneuroendocrinology. 1989;14:477-481.PubMedCrossRefGoogle Scholar
  44. 44.
    Esler M. Depressive illness, the sympathetic nervous system and cardiac risk. J Hypertens. 2009;27:2349-2350.PubMedCrossRefGoogle Scholar
  45. 45.
    Grassi G, Colombo M, Seravalle G, et al. Dissociation between muscle and skin sympathetic nerve activity in essential hypertension, obesity, and congestive heart failure. Hypertension. 1998;31:64-67.PubMedCrossRefGoogle Scholar
  46. 46.
    Krum H, Schlaich MP, Whitbourn R, et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009;373:1275-1281.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Limited 2011

Authors and Affiliations

  1. 1.Hypertension Thrombosis and Vascular Biology DivisionBaker IDI Heart and Diabetes InstituteMelbourneAustralia

Personalised recommendations