An Integrative Assessment of the Psychophysiologic Alterations in Young Women With Recurrent Major Depressive Disorder

Objective Alterations in neuroelectrical activities coincide with major depressive disorder (MDD). This study examines the pattern of cerebral activity and cardiac autonomic parameters of euthymic women with recurrent MDD. Methods Resting electroencephalograms and electrocardiograms were recorded from 20 women with MDD receiving escitalopram and 40 matched and healthy women. We computed frontal alpha asymmetry to evaluate the interhemispheric balance. Parameters of heart rate variability were extracted to assess cardiac autonomic control. Sample entropy was used to assess the complexity of neurocardiac dynamics. The relationship between cardiovagal activity and alpha electroencephalogram was examined with a coherence analysis. Results Multivariable analysis of variance revealed a differential pattern of psychophysiologic variables between MDD patients and controls (p = .03). MDD was associated with a tendency toward lower left frontal activity (−0.06 [standard deviation = 0.14] versus 0.04 [0.17] ln&mgr;V2, p = .04). Discriminant analysis demonstrated more right frontal activation, a lower high-frequency heart rate power spectrum, and a higher ratio of the low- to high-frequency heart rate power spectrum in patients with MDD compared with controls. Residual depressive symptoms (r = −0.09 to 0.11, p = .63–.99) and escitalopram dosage (r = −0.09 to 0.28, p = .22–.84) were not correlated with autonomic measures. Coherence between normalized high-frequency component of the heart rate power spectrum and alpha power was not significant (F3, p = .27; F4, p = .16). Conclusions Euthymic women with recurrent MDD have a distinctive psychophysiologic profile. This profile may reflect altered frontal activation and a reduced cardiovagal tone in depression. Abbreviations MDD = major depressive disorder EEG = electroencephalogram HRV = heart rate variability ECG = electrocardiogram HDRS = Hamilton Depression Rating Scale SSRI = selective serotonin reuptake inhibitor EOG = electrooculogram RR = beat to beat NN = normal to normal LF = low-frequency component of the heart rate power spectrum HF = high-frequency component of the heart rate power spectrum SampEn = sample entropy MANCOVA = multivariate analysis of covariance

[1]  Pedro Ribeiro,et al.  EEG frontal asymmetry in the depressed and remitted elderly: is it related to the trait or to the state of depression? , 2011, Journal of affective disorders.

[2]  P. van de Borne,et al.  The impact of chronic primary insomnia on the heart rate – EEG variability link , 2009, Clinical Neurophysiology.

[3]  G. Juckel,et al.  Is successful electroconvulsive therapy related to stimulation of the vagal system? , 2010, Journal of affective disorders.

[4]  S. Debener,et al.  Is Resting Anterior EEG Alpha Asymmetry a Trait Marker for Depression? , 2000, Neuropsychobiology.

[5]  E Donchin,et al.  A new method for off-line removal of ocular artifact. , 1983, Electroencephalography and clinical neurophysiology.

[6]  H. Huikuri,et al.  Ambulatory ECG and analysis of heart rate variability in Parkinson's disease , 2001, Journal of neurology, neurosurgery, and psychiatry.

[7]  J. P. Kline,et al.  Differential Resting Quantitative Electroencephalographic Alpha Patterns in Women with Environmental Chemical Intolerance, Depressives, and Normals , 1998, Biological Psychiatry.

[8]  A. Raine,et al.  Genetic and environmental influences on frontal EEG asymmetry and alpha power in 9-10-year-old twins. , 2009, Psychophysiology.

[9]  Sandy Berger,et al.  Acute psychosis leads to increased QT variability in patients suffering from schizophrenia , 2007, Schizophrenia Research.

[10]  H. Barbas,et al.  Serial pathways from primate prefrontal cortex to autonomic areas may influence emotional expression , 2003, BMC Neuroscience.

[11]  Karl-Jürgen Bär,et al.  Relationship between cardiovagal modulation and psychotic state in patients with paranoid schizophrenia , 2008, Psychiatry Research.

[12]  C. Morillo,et al.  Cerebral hemispheric lateralization in cardiac autonomic control. , 1997, Archives of neurology.

[13]  Nitish V. Thakor,et al.  Monotonicity of approximate entropy during transition from awareness to unresponsiveness due to propofol anesthetic induction , 2006, IEEE Transactions on Biomedical Engineering.

[14]  J. Richman,et al.  Physiological time-series analysis using approximate entropy and sample entropy. , 2000, American journal of physiology. Heart and circulatory physiology.

[15]  K. Bär,et al.  The altered complexity of cardiovascular regulation in depressed patients , 2010, Physiological measurement.

[16]  H. Demaree,et al.  Brain lateralization of emotional processing: historical roots and a future incorporating "dominance". , 2005, Behavioral and cognitive neuroscience reviews.

[17]  N. Fox,et al.  Regional patterns of brain activity in adults with a history of childhood-onset depression: gender differences and clinical variability. , 2002, The American journal of psychiatry.

[18]  Hannu Kinnunen,et al.  Physical activity and heart rate variability measured simultaneously during waking hours. , 2010, American journal of physiology. Heart and circulatory physiology.

[19]  B. Penninx,et al.  Longitudinal Evidence for Unfavorable Effects of Antidepressants on Heart Rate Variability , 2010, Biological Psychiatry.

[20]  J. Davidson,et al.  Effects of Paroxetine and Venlafaxine XR on Heart Rate Variability in Depression , 2005, Journal of clinical psychopharmacology.

[21]  K. Felmingham,et al.  Impact of Depression and Antidepressant Treatment on Heart Rate Variability: A Review and Meta-Analysis , 2010, Biological Psychiatry.

[22]  J. Lanquart,et al.  Altered interaction between cardiac vagal influence and delta sleep EEG suggests an altered neuroplasticity in patients suffering from major depressive disorder , 2010, Acta psychiatrica Scandinavica.

[23]  R. Lane,et al.  Claude Bernard and the heart–brain connection: Further elaboration of a model of neurovisceral integration , 2009, Neuroscience & Biobehavioral Reviews.

[24]  Alfretia L Scarborough,et al.  Paroxetine increases heart rate variability in panic disorder. , 1997, Journal of clinical psychopharmacology.

[25]  Jae Youn Hwang,et al.  Differential pattern of heart rate variability in patients with schizophrenia , 2009, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[26]  K. Bär,et al.  Reduced cardio-respiratory coupling in acute alcohol withdrawal. , 2008, Drug and alcohol dependence.

[27]  N. Fox,et al.  Adverse Rearing Environments and Neural Development in Children: The Development of Frontal Electroencephalogram Asymmetry , 2011, Biological Psychiatry.

[28]  D. Sheehan,et al.  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. , 1998, The Journal of clinical psychiatry.

[29]  M. Javorka,et al.  Cardiac autonomic regulation is impaired in girls with major depression , 2010, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[30]  Jacob Cohen.  Statistical Power Analysis for the Behavioral Sciences , 1969, The SAGE Encyclopedia of Research Design.

[31]  Andreas Voss,et al.  Gender-dependent impact of major depression on autonomic cardiovascular modulation , 2011, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[32]  Andreas Voss,et al.  Reduced cardio-respiratory coupling after treatment with nortriptyline in contrast to S-citalopram. , 2010, Journal of affective disorders.

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

[34]  Ravi S. Menon,et al.  Ventral medial prefrontal cortex and cardiovagal control in conscious humans , 2007, NeuroImage.

[35]  Heather L. Urry,et al.  The stability of resting frontal electroencephalographic asymmetry in depression. , 2004, Psychophysiology.

[36]  M. Weinand,et al.  Heart Rate and Heart Rate Variability Changes in the Intracarotid Sodium Amobarbital Test , 2001, Epilepsia.

[37]  H. Huikuri,et al.  Abnormal heart rate variability as a manifestation of autonomic dysfunction in hemispheric brain infarction. , 1996, Stroke.

[38]  N. Fox,et al.  Long-term stability of frontal electroencephalographic asymmetry in adults with a history of depression and controls. , 2006, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[39]  E. Gordon,et al.  Early Life Stress Combined with Serotonin 3A Receptor and Brain-Derived Neurotrophic Factor Valine 66 to Methionine Genotypes Impacts Emotional Brain and Arousal Correlates of Risk for Depression , 2010, Biological Psychiatry.

[40]  Paul S. Foster,et al.  Cerebral moderation of cardiovascular functioning: A functional cerebral systems perspective , 2008, Clinical Neurophysiology.

[41]  K. Bär,et al.  The relation of ventromedial prefrontal cortex activity and heart rate fluctuations at rest , 2009, The European journal of neuroscience.

[42]  R. A. Bryant,et al.  Disorder specificity despite comorbidity: Resting EEG alpha asymmetry in major depressive disorder and post-traumatic stress disorder , 2010, Biological Psychology.

[43]  J. P. Kline,et al.  Can EEG asymmetry patterns predict future development of anxiety and depression? A preliminary study , 2006, Biological Psychology.

[44]  R. Balon,et al.  Effects of nortriptyline and paroxetine on QT variability in patients with panic disorder , 2000, Depression and anxiety.

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

[46]  P. Holmans,et al.  Genetics of recurrent early‐onset depression (GenRED): Design and preliminary clinical characteristics of a repository sample for genetic linkage studies , 2003, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[47]  Petr Bob,et al.  Dissociation, cognitive conflict and nonlinear patterns of heart rate dynamics in patients with unipolar depression , 2009, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[48]  Maurizio Fava,et al.  Frontal EEG predictors of treatment outcome in major depressive disorder , 2009, European Neuropsychopharmacology.

[49]  D M Sheppard,et al.  Individualized Alpha Activity and Frontal Asymmetry in Major Depression , 2011, Clinical EEG and neuroscience.

[50]  J. Ickovics,et al.  Effects of propranolol on recovery of heart rate variability following acute myocardial infarction and relation to outcome in the Beta-Blocker Heart Attack Trial. , 2003, The American journal of cardiology.

[51]  Orrin Devinsky,et al.  Hemispheric influence on autonomic modulation and baroreflex sensitivity , 2001, Annals of neurology.

[52]  J. Chang,et al.  Changes in heart rate dynamics of patients with schizophrenia treated with risperidone , 2010, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[53]  Sandy Berger,et al.  Autonomy of Autonomic Dysfunction in Major Depression , 2009, Psychosomatic medicine.

[54]  R. Carney,et al.  Association of depression with reduced heart rate variability in coronary artery disease. , 1995, The American journal of cardiology.

[55]  R. C. Oldfield.  The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[56]  H. Scheinin,et al.  The effects of amitriptyline, citalopram and reboxetine on autonomic nervous system , 2001, Psychopharmacology.

[57]  E. Vittinghoff,et al.  Depressive symptoms, health behaviors, and risk of cardiovascular events in patients with coronary heart disease. , 2008, JAMA.

[58]  M. Hamilton.  A RATING SCALE FOR DEPRESSION , 1960, Journal of neurology, neurosurgery, and psychiatry.

[59]  A. Heath,et al.  Genetic and environmental influences on frontal EEG asymmetry: A twin study , 2006, Biological Psychology.

[60]  Nathan A. Fox,et al.  Autonomic nervous system reactivity to positive and negative mood induction: The role of acute psychological responses and frontal electrocortical activity , 2011, Biological Psychology.

[61]  M. Dumont,et al.  A study of the dynamic interactions between sleep EEG and heart rate variability in healthy young men , 2003, Clinical Neurophysiology.

[62]  Yi-Yuan Tang,et al.  Central and autonomic nervous system interaction is altered by short-term meditation , 2009, Proceedings of the National Academy of Sciences.