Motor activity and autonomic cardiac functioning in major depressive disorder.

BACKGROUND The daily pattern of motor activity and the autonomic cardiovascular regulation were studied in major depression to quantify changes in psychomotor function and autonomic cardiac functioning. Additionally, relationships between motor activity parameters, cardiovascular measures and specific clinical features were examined. METHODS Wrist-actigraphy was used to monitor 24-h motor activity for 67 unmedicated (unipolar) depressed inpatients and 64 control subjects. During supine rest, spectral analysis was applied to assess HR and SBP variability, a baroreflex sensitivity (BRS) index and the respiratory frequency, in addition to mean heart rate (HR) and blood pressure (BP) levels for the patient group and a second control group (N=51). RESULTS The patients showed a lower motor activity level and a reduced fragmentation of motor activity during wake, and a higher motor activity level and a decreased immobility during sleep. The mean HR and DBP level and the respiratory frequency were higher in the patient group than in the control group, but no differences in HR and SBP variability or BRS were found. Furthermore, motor activity parameters and cardiovascular measures of the patients were related to agitation and retardation and overall, patients with lower motor activity levels demonstrated lower SBP levels. CONCLUSIONS This study confirms that the 24-h pattern of motor activity is altered in unmedicated depressed inpatients, but limited evidence was found for an autonomic cardiac dysfunction. Within the patient group there were relationships between motor activity parameters, cardiovascular measures, and clinical features, but the underlying neurobiological pathways need to be further explored.

[1]  J. Bigger,et al.  Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction , 1998, The Lancet.

[2]  R. Cohen,et al.  Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. , 1981, Science.

[3]  J. Endicott,et al.  A diagnostic interview: the schedule for affective disorders and schizophrenia. , 1978, Archives of general psychiatry.

[4]  D. Rubin.  Multiple imputation for nonresponse in surveys , 1989 .

[5]  G. Heninger,et al.  EFFECTS OF LITHIUM CARBONATE ON MOTOR ACTIVITY IN MANIA AND DEPRESSION , 1977, The Journal of nervous and mental disease.

[6]  R. Hirschfeld.  History and evolution of the monoamine hypothesis of depression. , 2000, The Journal of clinical psychiatry.

[7]  H Just,et al.  Reflex versus tonic vagal activity as a prognostic parameter in patients with sustained ventricular tachycardia or ventricular fibrillation. , 1994, Circulation.

[8]  C. R. Cloninger,et al.  A psychobiological model of temperament and character. , 1993, Archives of general psychiatry.

[9]  E Länsimies,et al.  Age and gender dependency of baroreflex sensitivity in healthy subjects. , 1998, Journal of applied physiology.

[10]  K. Starke,et al.  Effects of Inhibitors of Neuronal Uptake of 5‐HT on Sympathetic Cardiovascular Regulation , 1992, Journal of cardiovascular pharmacology.

[11]  A. Glassman.  Cardiovascular effects of antidepressant drugs: updated , 1998, The Journal of clinical psychiatry.

[12]  N. Dantchev,et al.  The measurement of retardation in depression. , 1998, The Journal of clinical psychiatry.

[13]  A. J. Man in 't Veld,et al.  Cardiovascular variability in major depressive disorder and effects of imipramine or mirtazapine (Org 3770). , 1996, Journal of clinical psychopharmacology.

[14]  R. Balon,et al.  Depression and heart rate variability , 1995, Biological Psychiatry.

[15]  J. Helzer,et al.  Smoking, smoking cessation, and major depression. , 1990, JAMA.

[16]  J. Staessen,et al.  Influence of demographic, anthropometric and lifestyle characteristics on heart rate and its variability in the population. , 1999, Journal of hypertension.

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

[18]  C. R. Cloninger,et al.  The relationship of personality to mood and anxiety states: a dimensional approach. , 1992, Journal of psychiatric research.

[19]  R. Cohen,et al.  Hemodynamic regulation: investigation by spectral analysis. , 1985, The American journal of physiology.

[20]  N. Simionescu,et al.  The Cardiovascular System , 1983 .

[21]  Jagmeet P. Singh,et al.  Reduced heart rate variability and new-onset hypertension: insights into pathogenesis of hypertension: the Framingham Heart Study. , 1998, Hypertension.

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

[23]  A. Luke,et al.  Relationship between blood pressure and body mass index in lean populations. , 1997, Hypertension.

[24]  T. Rechlin.  The Effect of Amitriptyline, Doxepin, Fluvoxamine, and Paroxetine Treatment on Heart Rate Variability , 1994, Journal of clinical psychopharmacology.

[25]  J. Goldberg.  Evidence for a biochemical lesion in depression. , 2000 .

[26]  D. Kupfer,et al.  Sleep EEG and motor activity as indicators in affective states. , 1975, Neuropsychobiology.

[27]  G. Marijnissen,et al.  The temperament and character inventory in major depression. , 2002, Journal of affective disorders.

[28]  D. Buss,et al.  Preschool Activity Level: Personality Correlates and Developmental Implications. , 1980 .

[29]  J. Wakelin.  Fluvoxamine in the treatment of the older depressed patient; double-blind, placebo-controlled data. , 1986, International clinical psychopharmacology.

[30]  J. H. M. Tulen,et al.  Quantification of the dynamic behavior over time of narrow-band components present in heart rate variability by means of the instantaneous amplitude and frequency , 2005, Comput. Biol. Medicine.

[31]  R. Russell,et al.  Selective breeding for increased cholinergic function: biometrical genetic analysis of muscarinic responses. , 1992, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[32]  H. Kamphuisen,et al.  Ambulatory activity monitoring during sleep: an evaluation of internight and intrasubject variability in healthy persons aged 50-98 years. , 1993, Sleep.

[33]  Helen Brown,et al.  Applied Mixed Models in Medicine , 2000, Technometrics.

[34]  J. Halter,et al.  Tricyclic antidepressants and supine, standing, and exercise plasma norepinephrine levels , 1983, Clinical pharmacology and therapeutics.

[35]  J. Ballenger,et al.  Cardiovascular effects of imipramine, fluvoxamine, and placebo in depressed outpatients. , 1993, The Journal of clinical psychiatry.

[36]  J. Aasman,et al.  The Psychophysiology of Cardiovascular Control , 1985 .

[37]  J. Korf,et al.  5-Hydroxyindoleacetic Acid Levels in the Cerebrospinal Fluid of Depressive Patients treated with Probenecid , 1970, Nature.

[38]  H. Sackeim,et al.  Psychomotor symptoms of depression. , 1997, The American journal of psychiatry.

[39]  A. J. Man in 't Veld,et al.  Anxiety and autonomic regulation in major depressive disorder: an exploratory study. , 1996, Journal of affective disorders.

[40]  J. Weiss,et al.  Effects of Antidepressant Drugs on Rats Bred for Low Activity in the Swim Test , 1998, Pharmacology Biochemistry and Behavior.

[41]  E. Toft,et al.  Heart rate variability and plasma lipids in men with and without ischaemic heart disease. , 1999, Atherosclerosis.

[42]  D J Widlöcher,et al.  Psychomotor retardation: clinical, theoretical, and psychometric aspects. , 1983, The Psychiatric clinics of North America.

[43]  J. Reggers,et al.  Temperament and character inventory (TCI) and depression. , 1999, Journal of psychiatric research.

[44]  Alan D. Lopez,et al.  Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study , 1997, The Lancet.

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

[46]  C. Halverson,et al.  The Relations of Mechanically Recorded Activity Level to Varieties of Preschool Play Behavior. , 1973 .

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

[48]  D. Overstreet,et al.  Ontogeny of Muscarinic Cholinergic Supersensitivity in the Flinders Sensitive Line Rat , 1999, Pharmacology Biochemistry and Behavior.

[49]  C. R. Cloninger,et al.  Relationships between Cloninger's, Zuckerman's, and Eysenck's dimensions of personality. , 1996, Personality and individual differences.

[50]  C. Nemeroff,et al.  The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment. , 1998, Archives of general psychiatry.

[51]  H V Huikuri,et al.  Heart rate variability in coronary artery disease , 1995, Journal of internal medicine.

[52]  Dennis S. Charney,et al.  Neurobiology of Mental Illness , 2004 .

[53]  P. Sullivan,et al.  Genetic epidemiology of major depression: review and meta-analysis. , 2000, The American journal of psychiatry.

[54]  A. Schatzberg,et al.  Psychotic (delusional) major depression: should it be included as a distinct syndrome in DSM-IV? , 1992, The American journal of psychiatry.

[55]  I. Anderson,et al.  Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability. , 2000, Journal of affective disorders.

[56]  Carmine M Pariante,et al.  Glucocorticoid receptors in major depression: relevance to pathophysiology and treatment , 2001, Biological Psychiatry.

[57]  A Malliani,et al.  Interpreting oscillations of muscle sympathetic nerve activity and heart rate variability , 2000, Journal of hypertension.

[58]  C. Taylor,et al.  Tonic arousal and activity: Relationships to personality and personality disorder traits in panic patients , 1988, Psychiatry Research.

[59]  Richard Balon,et al.  Heart rate variability in patients with major depression , 1991, Psychiatry Research.

[60]  D L Eckberg,et al.  Influence of Cigarette Smoking on Human Autonomic Function , 1993, Circulation.

[61]  S. Tuinier,et al.  Two steps forward, one step back; paradigmatic changes in psychiatry , 2001, Journal of Neural Transmission.

[62]  C. R. Cloninger,et al.  The genetics and psychobiology of the seven-factor model of personality. , 1998 .

[63]  I. Hindmarch.  A Review of the Psychomotor Effects of Paroxetine , 1992, International clinical psychopharmacology.

[64]  D. Levy,et al.  Impact of reduced heart rate variability on risk for cardiac events. The Framingham Heart Study. , 1996, Circulation.

[65]  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.

[66]  J. Vaughan.  Measuring Behavior 2000 , 2001 .

[67]  F. Goodwin,et al.  Urinary 3-methoxy-4-hydroxyphenylglycol circadian rhythm. Early timing (phase-advance) in manic-depressives compared with normal subjects. , 1980, Archives of general psychiatry.

[68]  Alan D. Lopez,et al.  Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study , 1997, The Lancet.

[69]  J. Korf,et al.  Retarded depression and the dopamine metabolism , 2004, Psychopharmacologia.

[70]  F. Bloom,et al.  Psychopharmacology: The Fourth Generation of Progress , 1995 .

[71]  P. Joyce,et al.  Predictors of drug response in depression. , 1989, Archives of general psychiatry.

[72]  F. Holsboer,et al.  Stress, hypercortisolism and corticosteroid receptors in depression: implications for therapy. , 2001, Journal of affective disorders.

[73]  G. Parati,et al.  Smoking impairs baroreflex sensitivity in humans. , 1997, The American journal of physiology.

[74]  D. Eckberg,et al.  Important influence of respiration on human R-R interval power spectra is largely ignored. , 1993, Journal of applied physiology.

[75]  Dick F. Swaab,et al.  Gravitational artefact in frequency spectra of movement acceleration: implications for actigraphy in young and elderly subjects , 1996, Journal of Neuroscience Methods.

[76]  R. J. Leo,et al.  Movement disorders associated with the serotonin selective reuptake inhibitors. , 1996, The Journal of clinical psychiatry.

[77]  Pierre Denise,et al.  Circadian pattern of motor activity in major depressed patients undergoing antidepressant therapy: Relationship between actigraphic measures and clinical course , 1994, Psychiatry Research.

[78]  Hartmut Schächinger,et al.  Cardiovascular Indices of Peripheral and Central Sympathetic Activation , 2001, Psychosomatic medicine.

[79]  M. Hamilton,et al.  Development of a rating scale for primary depressive illness. , 1967, The British journal of social and clinical psychology.

[80]  D. Kupfer,et al.  Psychomotor activity in mania. , 1974, Archives of general psychiatry.

[81]  R. Post,et al.  Motor activity and affective illness. The relationship of amplitude and temporal distribution to changes in affective state. , 1985, Archives of general psychiatry.

[82]  A. Littman.  Review of psychosomatic aspects of cardiovascular disease. , 1993, Psychotherapy and psychosomatics.

[83]  Monte S. Buchsbaum,et al.  Sensation seeking and its biological correlates. , 1980 .

[84]  A. Guyton,et al.  Textbook of Medical Physiology , 1961 .

[85]  H. Kemper,et al.  Validity and repeatability of a modified Baecke questionnaire on physical activity. , 1995, International journal of epidemiology.

[86]  E. Robins,et al.  Research diagnostic criteria: rationale and reliability. , 1978, Archives of general psychiatry.

[87]  S. Roose,et al.  Depression, heart disease, and tricyclic antidepressants. , 1989, The Journal of clinical psychiatry.

[88]  I. Hickie,et al.  Sub-typing depression, III. Development of a clinical algorithm for melancholia and comparison with other diagnostic measures , 1995, Psychological Medicine.

[89]  J. Schildkraut,et al.  The catecholamine hypothesis of affective disorders: a review of supporting evidence. , 1965, The American journal of psychiatry.

[90]  Martin H. Teicher.  Actigraphy and Motion Analysis: New Tools for Psychiatry , 1995, Harvard review of psychiatry.

[91]  Jin‐Shang Wu,et al.  Correlation between serum lipid concentrations and psychological distress , 2001, Psychiatry Research.

[92]  G. D'Alonzo,et al.  Actigraphy: a means of assessing circadian patterns in human activity. , 1990, Chronobiology international.

[93]  J. Fahrenberg,et al.  Progress in Ambulatory Assessment , 2001 .

[94]  R. Post,et al.  Motor activity in depressed patients treated with carbamazepine , 1987, Biological Psychiatry.

[95]  S. Shacham,et al.  A shortened version of the Profile of Mood States. , 1983, Journal of personality assessment.

[96]  S. Porges,et al.  Effects of alprazolam and imipramine on parasympathetic cardiac control in patients with generalized anxiety disorder , 1992, Psychopharmacology.

[97]  B. Penninx,et al.  Depression and cardiac mortality: results from a community-based longitudinal study. , 2001, Archives of general psychiatry.

[98]  K Dave,et al.  A CRITICAL APPRAISAL , 2002 .

[99]  Robert Plutchik,et al.  Biological foundations of emotion , 1986 .

[100]  H G Zapotoczky,et al.  Increased heart rate in depressed subjects in spite of unchanged autonomic balance? , 1998, Journal of affective disorders.

[101]  D. Janowsky,et al.  A cholinergic-adrenergic hypothesis of mania and depression. , 1972, Lancet.

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

[103]  M. Mirmiran,et al.  Alterations in the circadian rest-activity rhythm in aging and Alzheimer's disease , 1990, Biological Psychiatry.

[104]  I. Heuser,et al.  Antidepressive treatment with amitriptyline and paroxetine: comparable effects on heart rate variability. , 2001, Journal of clinical psychopharmacology.

[105]  P. Novak,et al.  Influence of respiration on heart rate and blood pressure fluctuations. , 1993, Journal of applied physiology.

[106]  Winni F. Hofman,et al.  Sleep-wake research in the Netherlands , 1999 .

[107]  J. Tulen,et al.  The exponential distribution applied to nonequidistantly sampled cardiovascular time series. , 1996, Computers and biomedical research, an international journal.

[108]  H Kuhs,et al.  Psychomotor activity in unipolar and bipolar depressive patients. , 1992, Psychopathology.

[109]  J. Passchier.  Effects of antidepressant treatment on subjective sleep characteristics of depressed patients , 2001 .

[110]  I Tobler,et al.  Monitoring of Long-Term Motor Activity in Depressed Patients , 1986, British Journal of Psychiatry.

[111]  A. Malliani,et al.  Heart rate variability. Standards of measurement, physiological interpretation, and clinical use , 1996 .

[112]  P. Grossman,et al.  Anxiety reduces baroreflex cardiac control in older adults with major depression. , 1999, Psychosomatic medicine.

[113]  M. Kikuya,et al.  Prognostic Significance of Blood Pressure and Heart Rate Variabilities: The Ohasama Study , 2000, Hypertension.

[114]  M. Thase,et al.  Depression, sleep, and antidepressants. , 1998, The Journal of clinical psychiatry.

[115]  M. Kupari,et al.  Short-term heart rate variability and factors modifying the risk of coronary artery disease in a population sample. , 1993, The American journal of cardiology.

[116]  Richard J. McPartland,et al.  Psychomotor activity in affective states. , 1974 .

[117]  I. Tobler,et al.  Circadian aspects of motor activity in depressed patients. , 1985, Acta psychiatrica Belgica.

[118]  A. Glassman.  Cigarette smoking: implications for psychiatric illness. , 1993, The American journal of psychiatry.

[119]  F. Holsboer,et al.  Antidepressants and hypothalamic-pituitary-adrenocortical regulation. , 1996, Endocrine reviews.

[120]  D. Overstreet.  Selective breeding for increased cholinergic function: Development of a new animal model of depression , 1986, Biological Psychiatry.

[121]  J. Cacioppo,et al.  Respiratory sinus arrhythmia: autonomic origins, physiological mechanisms, and psychophysiological implications. , 1993, Psychophysiology.

[122]  W. Gattaz,et al.  Cardiovascular effects of fluvoxamine and maprotiline in depressed patients , 2005, European Archives of Psychiatry and Clinical Neuroscience.

[123]  G. Parker,et al.  Classifying depression: should paradigms lost be regained? , 2000, The American journal of psychiatry.

[124]  S. Stahl.  Psychopharmacology of Antidepressants , 1997 .

[125]  P. Grossman,et al.  Respiratory sinus arrhythmia, cardiac vagal tone, and respiration: within- and between-individual relations. , 1993, Psychophysiology.

[126]  J E Frijters,et al.  A short questionnaire for the measurement of habitual physical activity in epidemiological studies. , 1982, The American journal of clinical nutrition.

[127]  C. Stewart,et al.  How antidepressants work: new perspectives on the pathophysiology of depressive disorder. , 2001, The British journal of psychiatry : the journal of mental science.

[128]  H. Middelkoop,et al.  45-hour continuous quintuple-site actimetry: relations between trunk and limb movements and effects of circadian sleep-wake rhythmicity. , 1997, Psychophysiology.

[129]  A. Malliani,et al.  Cardiovascular Neural Regulation Explored in the Frequency Domain , 1991, Circulation.

[130]  C. W. Hughes.  Emotion: Theory, Research and Experience , 1982 .

[131]  J. Bigger,et al.  Cardiovascular effects of fluoxetine in depressed patients with heart disease. , 1998, The American journal of psychiatry.

[132]  C. Hayward.  Psychiatric illness and cardiovascular disease risk. , 1995, Epidemiologic reviews.

[133]  B. Brodie,et al.  Interaction of reserpine, serotonin, and lysergic acid diethylamide in brain. , 1955, Science.

[134]  H. Persky,et al.  Psychological Stress and Endocrine Functions: Blood Levels of Adrenocortical and Thyroid Hormones in Acutely Disturbed Patients , 1956, Psychosomatic medicine.

[135]  J. Tuomilehto,et al.  Heart rate and blood pressure variability and baroreflex sensitivity in hypercholesterolaemia. , 1995, Clinical physiology.

[136]  T. Kitamura,et al.  Temperament and Character Inventory (TCI) as predictors of depression among Japanese college students. , 2000, Journal of clinical psychology.

[137]  I. Hindmarch,et al.  Effects of fluvoxamine and dothiepin on psychomotor abilities in healthy volunteers , 1996, Pharmacology Biochemistry and Behavior.

[138]  G. Kerkhof,et al.  Plasma arginine vasopressin and motor activity in major depression , 1998, Biological Psychiatry.

[139]  A. Young,et al.  Mood and neuropsychological function in depression: the role of corticosteroids and serotonin , 1998, Psychological Medicine.

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

[141]  S. Tuinier,et al.  Dimensional classification and behavioral pharmacology of personality disorders; a review and hypothesis , 1995, European Neuropsychopharmacology.

[142]  G. Parati,et al.  How to measure baroreflex sensitivity: from the cardiovascular laboratory to daily life , 2000, Journal of hypertension.

[143]  H. Meltzer,et al.  Lower serum high‐density lipoprotein cholesterol (HDL‐C) in major depression and in depressed men with serious suicidal attempts: relationship with immune‐inflammatory markers , 1997, Acta psychiatrica Scandinavica.

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

[145]  A. V. van Roon,et al.  Spectral analysis of hemodynamics during infusions of epinephrine and norepinephrine in men. , 1994, Journal of applied physiology.

[146]  J. Gorman,et al.  Heart rate variability in depressive and anxiety disorders. , 2000, American heart journal.

[147]  A Stys,et al.  Current clinical applications of heart rate variability , 1998, Clinical cardiology.

[148]  J. Gibbons.  CORTISOL SECRETION RATE IN DEPRESSIVE ILLNESS. , 1964, Archives of general psychiatry.

[149]  A. Vingerhoets,et al.  Depressive Symptoms, Social Support, and Lipid Profile in Healthy Middle-Aged Women , 1997, Psychosomatic medicine.

[150]  C. Tangen,et al.  Depressive Symptoms and Risks of Coronary Heart Disease and Mortality in Elderly Americans , 2000 .

[151]  P. Mitchell,et al.  Subtyping depression: testing algorithms and identification of a tiered model. , 1999, The Journal of nervous and mental disease.

[152]  H. Eysenck.  Biological Basis of Personality , 1963, Nature.

[153]  J. Thayer,et al.  Heart period variability and depressive symptoms: gender differences , 1998, Biological Psychiatry.

[154]  Harris R. Lieberman,et al.  Circadian rhythms of activity in healthy young and elderly humans , 1989, Neurobiology of Aging.

[155]  S. Roose,et al.  Treating the depressed patient with cardiovascular problems. , 1992, The Journal of clinical psychiatry.

[156]  Brian Knutson,et al.  Selective alteration of personality and social behavior by serotonergic intervention. , 1998, The American journal of psychiatry.

[157]  J. Polivy,et al.  Dieting and binging: A causal analysis. , 1985 .

[158]  M. Lemke,et al.  Motor activity and perception of sleep in depressed patients. , 1999, Journal of psychiatric research.

[159]  G. Parati,et al.  Spectral analysis of blood pressure and heart rate variability in evaluating cardiovascular regulation. A critical appraisal. , 1995, Hypertension.

[160]  L J Mulder,et al.  Heart rate variability spectra based on non-equidistant sampling: the spectrum of counts and the instantaneous heart rate spectrum. , 1994, Medical engineering & physics.

[161]  H V Huikuri,et al.  Heart rate variability in systemic hypertension. , 1996, The American journal of cardiology.

[162]  H. Robbe,et al.  Assessment of baroreceptor reflex sensitivity by means of spectral analysis. , 1987, Hypertension.

[163]  G. Parati,et al.  Dynamic Modulation of Baroreflex Sensitivity in Health and Disease , 2001, Annals of the New York Academy of Sciences.

[164]  J. A. Boer,et al.  Handbook of depression and anxiety , 2003 .

[165]  I. Hickie,et al.  Classifying Depression by Mental State Signs , 1990, British Journal of Psychiatry.

[166]  M. Gorfine,et al.  Effect of clinical doses of fluoxetine on psychological variables in healthy volunteers. , 1998, American Journal of Psychiatry.

[167]  David S. Krantz,et al.  Automated physical activity monitoring: validation and comparison with physiological and self-report measures. , 1993, Psychophysiology.

[168]  J. Wardle,et al.  Cholesterol and psychological well-being. , 1995, Journal of psychosomatic research.

[169]  P. Moleman,et al.  Depressed In-Patients Respond Differently to Imipramine and Mirtazapine , 1999, Pharmacopsychiatry.

[170]  S. Hyman,et al.  The Molecular Foundations Of Psychiatry , 1993 .