Depression, the Autonomic Nervous System, and Coronary Heart Disease

Depression is a risk factor for medical morbidity and mortality in patients with coronary heart disease (CHD). Dysregulation of the autonomic nervous system (ANS) may explain why depressed patients are at increased risk. Studies of medically well, depressed psychiatric patients have found elevated levels of plasma catecholamines and other markers of altered ANS function compared with controls. Studies of depressed patients with CHD have also uncovered evidence of ANS dysfunction, including elevated heart rate, low heart rate variability, exaggerated heart rate responses to physical stressors, high variability in ventricular repolarization, and low baroreceptor sensitivity. All of these indicators of ANS dysfunction have been associated with increased risks of mortality and cardiac morbidity in patients with CHD. Further research is needed to determine whether ANS dysfunction mediates the effects of depression on the course and outcome of CHD, and to develop clinical interventions that improve cardiovascular autonomic regulation while relieving depression in patients with CHD. ANS = autonomic nervous system; CHD = coronary heart disease; HRV = heart rate variability; MI = myocardial infarction; NE = norepinephrine; SNS = sympathetic nervous system.

[1]  S. Roose,et al.  Perspectives on the relationship between cardiovascular disease and affective disorder. , 1990, The Journal of clinical psychiatry.

[2]  J. Halter,et al.  Dose-dependent suppression of norepinephrine appearance rate in plasma by clonidine in man. , 1984, The Journal of clinical endocrinology and metabolism.

[3]  D. Charney,et al.  Impaired presynaptic regulation of norepinephrine in schizophrenia. Effects of clonidine in schizophrenic patients and normal controls. , 1982, Archives of general psychiatry.

[4]  C. Shapiro,et al.  Autonomie Correlates of Antidepressant Treatment Using Heart-Rate Variability Analysis , 1998, Canadian journal of psychiatry. Revue canadienne de psychiatrie.

[5]  E. Fallen,et al.  Effect of sertraline on the recovery rate of cardiac autonomic function in depressed patients after acute myocardial infarction. , 2001, American heart journal.

[6]  Peter J. Schwartz,et al.  Baroreflex Sensitivity and Heart Rate Variability in the Identification of Patients at Risk for Life-Threatening Arrhythmias Implications for Clinical Trials , 2001 .

[7]  J. Gottdiener,et al.  The role of immune system parameters in the relationship between depression and coronary artery disease. , 2005, Psychosomatic medicine.

[8]  Phyllis K. Stein,et al.  Effects of Depression on QT Interval Variability After Myocardial Infarction , 2003, Psychosomatic medicine.

[9]  R. Califf,et al.  Depression and long-term mortality risk in patients with coronary artery disease. , 1996, The American journal of cardiology.

[10]  L. Griffith,et al.  Ambulatory electrocardiographic recordings at the time of fatal cardiac arrest. , 1985, The American journal of cardiology.

[11]  Robert M Carney,et al.  Association of anxiety with reduced baroreflex cardiac control in patients after acute myocardial infarction. , 2002, American heart journal.

[12]  U. Heidland,et al.  Left Ventricular Muscle Mass and Elevated Heart Rate Are Associated With Coronary Plaque Disruption , 2001, Circulation.

[13]  G. Lip,et al.  Mortality and Quality of Life 12 Months After Myocardial Infarction: Effects of Depression and Anxiety , 2001, Psychosomatic medicine.

[14]  H. Whiteford,et al.  CSF amine metabolites and depression , 1987, Psychiatry Research.

[15]  P. Vestergaard,et al.  Heart rate variation in patients treated with antidepressants. An index of anticholinergic effects? , 2004, Psychopharmacology.

[16]  G. Breithardt,et al.  Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. , 1996 .

[17]  S. Paige,et al.  Increases in heart rate variability with successful treatment in patients with major depressive disorder. , 1993, Psychopharmacology bulletin.

[18]  M. Linnoila,et al.  Norepinephrine and its metabolites in cerebrospinal fluid, plasma, and urine. Relationship to hypothalamic-pituitary-adrenal axis function in depression. , 1988, Archives of general psychiatry.

[19]  P. Edwards,et al.  Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics. , 1995, Circulation.

[20]  V. Starc,et al.  Beat-to-beat QT interval variability in coronary patients. , 2000, Journal of electrocardiology.

[21]  M. Dawson,et al.  Autonomic correlates of depression and clinical improvement following electroconvulsive shock therapy. , 1977, Psychophysiology.

[22]  P. Schwartz,et al.  Cardiac Arrhythmias Elicited by Interaction Between Acute Myocardial Ischemia and Sympathetic Hyperactivity: A New Experimental Model for the Study of Antiarrhythmic Drugs , 1981, Journal of cardiovascular pharmacology.

[23]  J. Denollet,et al.  Personality and Mortality After Myocardial Infarction , 1995, Psychosomatic medicine.

[24]  D. Cardinali,et al.  Cardiovascular tests of autonomic function and sympathetic skin responses in patients with major depression. , 1995, Journal of neurology, neurosurgery, and psychiatry.

[25]  R. Carney,et al.  Ventricular tachycardia and psychiatric depression in patients with coronary artery disease. , 1993, The American journal of medicine.

[26]  P. Coumel,et al.  Changes in Repolarization Dynamicity and the Assessment of the Arrhythmic Risk , 1997, Pacing and clinical electrophysiology : PACE.

[27]  C. Zarins,et al.  Retarding effect of lowered heart rate on coronary atherosclerosis. , 1984, Science.

[28]  N. Frasure-smith,et al.  Depression and 18-month prognosis after myocardial infarction. , 1995, Circulation.

[29]  S. Connolly,et al.  Depression and risk of sudden cardiac death after acute myocardial infarction: testing for the confounding effects of fatigue. , 1999, Psychosomatic Medicine.

[30]  R. Balon,et al.  Effect of imipramine treatment on heart rate variability measures. , 1992, Neuropsychobiology.

[31]  M. Pascualy,et al.  Short-term sertraline treatment suppresses sympathetic nervous system activity in healthy human subjects , 2001, Psychoneuroendocrinology.

[32]  S. Willich,et al.  Circadian variation in the frequency of sudden cardiac death. , 1987, Circulation.

[33]  J. Halter,et al.  High levels of plasma catecholamines in dexamethasone-resistant depressed patients. , 1983, The American journal of psychiatry.

[34]  J. Miller,et al.  Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. , 1987, The American journal of cardiology.

[35]  A. Timmis,et al.  Relation between heart rate variability early after acute myocardial infarction and long-term mortality. , 1994, The American journal of cardiology.

[36]  M. Allen,et al.  Enhanced cardiovascular and catecholamine responses in women with depressive symptoms. , 1998, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[37]  S. Julius,et al.  Association of tachycardia with morbidity and mortality: pathophysiological considerations. , 1997, Journal of human hypertension.

[38]  A. Day,et al.  Depression and Anxiety As Predictors of Outcome After Myocardial Infarction , 2000, Psychosomatic medicine.

[39]  D. Ahern,et al.  Biobehavioral variables and mortality or cardiac arrest in the Cardiac Arrhythmia Pilot Study (CAPS). , 1990, The American journal of cardiology.

[40]  S. Giampaoli,et al.  Heart rate as a predictor of mortality: the MATISS project. , 2001, American journal of public health.

[41]  P. Rizzon,et al.  Depression but not anxiety influences the autonomic control of heart rate after myocardial infarction. , 2001, American heart journal.

[42]  J. Fleiss,et al.  Frequency domain measures of heart period variability to assess risk late after myocardial infarction. , 1993, Journal of the American College of Cardiology.

[43]  R. Carney,et al.  Major depression, heart rate, and plasma norepinephrine in patients with coronary heart disease , 1999, Biological Psychiatry.

[44]  R. Carney,et al.  Depression as a risk factor for mortality after acute myocardial infarction. , 2003, The American journal of cardiology.

[45]  H. Lahmeyer,et al.  Cardiac regulation and depression. , 1987, Journal of psychiatric research.

[46]  D. Musselman,et al.  Depression, alterations in platelet function, and ischemic heart disease. , 2005, Psychosomatic medicine.

[47]  N. Frasure-smith,et al.  Depression and 1-year prognosis in unstable angina. , 2000, Archives of internal medicine.

[48]  S. G. Rosen,et al.  Norepinephrine metabolism in humans. Kinetic analysis and model. , 1987, The Journal of clinical investigation.

[49]  B. Jacotot.  [Atherosclerosis: basic mechanisms]. , 1983, La semaine des hopitaux : organe fonde par l'Association d'enseignement medical des hopitaux de Paris.

[50]  K. Davis,et al.  Overview: toward a dysregulation hypothesis of depression. , 1985, The American journal of psychiatry.

[51]  R. Carney,et al.  The relationship between heart rate, heart rate variability and depression in patients with coronary artery disease. , 1988, Journal of psychosomatic research.

[52]  K. Williams,et al.  Atherosclerosis--an inflammatory disease. , 1999, The New England journal of medicine.

[53]  Richard Balon,et al.  Effect of Posture and Isoproterenol on Beat-to-Beat Heart Rate and QT Variability , 2000, Neuropsychobiology.

[54]  J. Halter,et al.  Sympathetic nervous system activity in major depression. Basal and desipramine-induced alterations in plasma norepinephrine kinetics. , 1994, Archives of general psychiatry.

[55]  D. Claus,et al.  Decreased heart rate variability parameters in amitriptyline treated depressed patients: biological and clinical significance , 1995, European Psychiatry.

[56]  A J Camm,et al.  Baroreflex Sensitivity and Heart Rate Variability in the Identification of Patients at Risk for Life-Threatening Arrhythmias: Implications for Clinical Trials , 2001, Circulation.

[57]  T. Rechlin,et al.  Heart Rate Variability in Depressed Patients and Differential Effects of Paroxetine and Amitriptyline on Cardiovascular Autonomic Functions , 1994, Pharmacopsychiatry.

[58]  James A. Blumenthal,et al.  Depression, Heart Rate Variability, and Acute Myocardial Infarction , 2001, Circulation.

[59]  G. Fricchione,et al.  Relation between myocardial infarction, depression, hostility, and death. , 1999, American heart journal.

[60]  B. Pollock,et al.  Comparison of paroxetine and nortriptyline in depressed patients with ischemic heart disease. , 1998, JAMA.

[61]  J. .. Abildskov,et al.  Influence of sympathetic tone on ventricular fibrillation threshold during experimental coronary occlusion. , 1975, The American journal of cardiology.

[62]  R. Carney,et al.  Correlation of heart rate variability with clinical and angiographic variables and late mortality after coronary angiography. , 1988, The American journal of cardiology.

[63]  H. Hazama,et al.  R‐R Intervals of ECG in Depression , 1985, Folia psychiatrica et neurologica japonica.

[64]  W. Kaschka,et al.  Are affective disorders associated with alterations of heart rate variability? , 1994, Journal of affective disorders.

[65]  R. Carney,et al.  Depression as a risk factor for cardiac mortality and morbidity: a review of potential mechanisms. , 2002, Journal of psychosomatic research.

[66]  M. Trovati,et al.  Role of catecholamines in platelet function: pathophysiological and clinical significance , 1996, European journal of clinical investigation.

[67]  J. Fleiss,et al.  Frequency Domain Measures of Heart Period Variability and Mortality After Myocardial Infarction , 1992, Circulation.

[68]  H. Katus,et al.  Course and prognostic implications of QT interval and QT interval variability after primary coronary angioplasty in acute myocardial infarction. , 2001, Journal of the American College of Cardiology.

[69]  M. Esler,et al.  The peripheral kinetics of norepinephrine in depressive illness. , 1982, Archives of general psychiatry.

[70]  R. Candinas,et al.  Role of the sympathetic nervous system in the genesis of ventricular arrhythmia. , 1990, Circulation.

[71]  R. Balon,et al.  Effect of fluoxetine, pemoline and placebo on heart period and QT variability in normal humans. , 2003, Journal of psychosomatic research.

[72]  J. Fahrenberg,et al.  Cortisol, ACTH, and cardiovascular response to a cognitive challenge paradigm in aging and depression. , 1995, The American journal of physiology.

[73]  Rungroj Krittayaphong,et al.  Heart Rate Variability in Patients with Coronary Artery Disease: Differences in Patients with Higher and Lower Depression Scores , 1997, Psychosomatic medicine.

[74]  R R Miller,et al.  Analysis of ambulatory electrocardiograms in 15 patients during spontaneous ventricular fibrillation with special reference to preceding arrhythmic events. , 1983, Journal of the American College of Cardiology.

[75]  R. Carney,et al.  Major depressive disorder predicts cardiac events in patients with coronary artery disease. , 1988, Psychosomatic medicine.

[76]  H A Lindberg,et al.  Heart rate as a prognostic factor for coronary heart disease and mortality: findings in three Chicago epidemiologic studies. , 1980, American journal of epidemiology.

[77]  P. Shapiro,et al.  Depression and the course of coronary artery disease. , 1998, The American journal of psychiatry.

[78]  P. Schwartz,et al.  Autonomic mechanisms and sudden death. New insights from analysis of baroreceptor reflexes in conscious dogs with and without a myocardial infarction. , 1988, Circulation.

[79]  H Calkins,et al.  Beat‐to‐Beat Repolarization Lability Identifies Patients at Risk for Sudden Cardiac Death , 1998, Journal of cardiovascular electrophysiology.

[80]  R. Carney,et al.  Change in Heart Rate and Heart Rate Variability During Treatment for Depression in Patients With Coronary Heart Disease , 2000, Psychosomatic medicine.

[81]  P. Grossman,et al.  Association of depressive symptoms with reduced baroreflex cardiac control in coronary artery disease. , 1999, American heart journal.

[82]  W. White,et al.  Depression as a risk factor for mortality after coronary artery bypass surgery , 2003, The Lancet.

[83]  O. Cameron.  Depression increases post-Mi mortality: how? , 1996, Psychosomatic medicine.

[84]  D. Murphy,et al.  High plasma norepinephrine levels in patients with major affective disorder. , 1982, The American journal of psychiatry.

[85]  K. Matthews,et al.  Platelets and coronary heart disease: potential psychophysiologic mechanisms. , 1991, Psychosomatic medicine.

[86]  Kenneth E Freedland,et al.  Depression, mortality, and medical morbidity in patients with coronary heart disease , 2003, Biological Psychiatry.

[87]  Abraham Weizman,et al.  Heart rate variability in patients with major depression. , 2004, Psychosomatics.

[88]  D. Mcleod,et al.  Major depression and cardiac autonomic control , 1997, Biological Psychiatry.

[89]  R. Carney,et al.  Depression as a risk factor for cardiac events in established coronary heart disease: A review of possible mechanisms , 1995, Annals of behavioral medicine : a publication of the Society of Behavioral Medicine.

[90]  J. Kjekshus,et al.  Importance of heart rate in determining beta-blocker efficacy in acute and long-term acute myocardial infarction intervention trials. , 1986, The American journal of cardiology.

[91]  W. Anderson,et al.  Assessment of human sympathetic nervous system activity from measurements of norepinephrine turnover. , 1988, Hypertension.

[92]  D. Kupfer,et al.  Resting plasma catecholamine concentrations in patients with depression and anxiety. , 1971, Archives of general psychiatry.

[93]  G. Breithardt,et al.  Affective disorders and survival after acute myocardial infarction. Results from the post-infarction late potential study. , 1991, European heart journal.

[94]  R S Paffenbarger,et al.  Heart rate and cardiovascular mortality: the Framingham Study. , 1987, American heart journal.

[95]  R. Carney,et al.  Severe depression is associated with markedly reduced heart rate variability in patients with stable coronary heart disease. , 2000, Journal of psychosomatic research.

[96]  D. Bush,et al.  Even minimal symptoms of depression increase mortality risk after acute myocardial infarction. , 2001, The American journal of cardiology.

[97]  Phyllis K. Stein,et al.  Association of depression witk reduced heart rate variability in coronary artery disease , 1995 .