The Phrenic Component of Acute Schizophrenia – A Name and Its Physiological Reality

Decreased heart rate variability (HRV) was shown for unmedicated patients with schizophrenia and their first-degree relatives, implying genetic associations. This is known to be an important risk factor for increased cardiac mortality in other diseases. The interaction of cardio-respiratory function and respiratory physiology has never been investigated in the disease although it might be closely related to the pattern of autonomic dysfunction. We hypothesized that increased breathing rates and reduced cardio-respiratory coupling in patients with acute schizophrenia would be associated with low vagal function. We assessed variability of breathing rates and depth, HRV and cardio-respiratory coupling in patients, their first-degree relatives and controls at rest. Control subjects were investigated a second time by means of a stress task to identify stress-related changes of cardio-respiratory function. A total of 73 subjects were investigated, consisting of 23 unmedicated patients, 20 healthy, first-degree relatives and 30 control subjects matched for age, gender, smoking and physical fitness. The LifeShirt®, a multi-function ambulatory device, was used for data recording (30 minutes). Patients breathe significantly faster (p<.001) and shallower (p<.001) than controls most pronouncedly during exhalation. Patients' breathing is characterized by a significantly increased amount of middle- (p<.001), high- (p<.001), and very high frequency fluctuations (p<.001). These measures correlated positively with positive symptoms as assessed by the PANSS scale (e.g., middle frequency: r = 521; p<.01). Cardio-respiratory coupling was reduced in patients only, while HRV was decreased in patients and healthy relatives in comparison to controls. Respiratory alterations might reflect arousal in acutely ill patients, which is supported by comparable physiological changes in healthy subjects during stress. Future research needs to further investigate these findings with respect to their physiological consequences for patients. These results are invaluable for researchers studying changes of biological signals prone to the influence of breathing rate and rhythm (e.g., functional imaging).

[1]  H. Huikuri,et al.  Schizophrenia and sudden cardiac death—A review , 2008, Nordic journal of psychiatry.

[2]  Elvina M. Chu,et al.  Heart rate variability response to mental arithmetic stress is abnormal in first-degree relatives of individuals with schizophrenia , 2009, Schizophrenia Research.

[3]  P. Caminal,et al.  Symbolic Dynamic Analysis of Relations Between Cardiac and Breathing Cycles in Patients on Weaning Trials , 2010, Annals of Biomedical Engineering.

[4]  P. Lalley.  Opioidergic and dopaminergic modulation of respiration , 2008, Respiratory Physiology & Neurobiology.

[5]  A Schirdewan,et al.  Forecasting of Life Threatening Arrhythmias Using the Compression Entropy of Heart Rate , 2004, Methods of Information in Medicine.

[6]  C. Janson,et al.  How often is diagnosis of COPD confirmed with spirometry? , 2010, Respiratory medicine.

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

[8]  M. Malik.  Heart Rate Variability , 1996, Clinical cardiology.

[9]  Servet Aker,et al.  Prevalence of Metabolic Syndrome among Inpatients with Schizophrenia , 2008, International journal of psychiatry in medicine.

[10]  H. Sauer,et al.  Decreased baroreflex sensitivity in acute schizophrenia. , 2007, Journal of applied physiology.

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

[12]  T. Tsumori,et al.  Amygdaloid axon terminals are in contact with trigeminal premotor neurons in the parvicellular reticular formation of the rat medulla oblongata , 2004, Brain Research.

[13]  P. Grossman,et al.  Paced respiratory sinus arrhythmia as an index of cardiac parasympathetic tone during varying behavioral tasks. , 1990, Psychophysiology.

[14]  Jeff H. Duyn,et al.  Modulation of spontaneous fMRI activity in human visual cortex by behavioral state , 2009, NeuroImage.

[15]  M. Tancer,et al.  Nonlinear Measures of Respiration: Respiratory Irregularity and Increased Chaos of Respiration in Patients with Panic Disorder , 2002, Neuropsychobiology.

[16]  Sandy Berger,et al.  Nonlinear relationship between electrodermal activity and heart rate variability in patients with acute schizophrenia. , 2011, Psychophysiology.

[17]  Walter A. Zin,et al.  Panic disorder and control of breathing , 2009, Respiratory Physiology & Neurobiology.

[18]  J. Tulen,et al.  Physiological responsivity to emotional pictures in schizophrenia. , 2005, Journal of psychiatric research.

[19]  Sandy Berger,et al.  Reduced cardio-respiratory coupling indicates suppression of vagal activity in healthy relatives of patients with schizophrenia , 2010, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[20]  J. Saul,et al.  Transfer function analysis of autonomic regulation. I. Canine atrial rate response. , 1989, The American journal of physiology.

[21]  B. Krieger,et al.  Calibration of respiratory inductive plethysmograph during natural breathing. , 1989, Journal of applied physiology.

[22]  S. Kay,et al.  The positive and negative syndrome scale (PANSS) for schizophrenia. , 1987, Schizophrenia bulletin.

[23]  M. Haxhiu,et al.  CNS innervation of vagal preganglionic neurons controlling peripheral airways: a transneuronal labeling study using pseudorabies virus. , 1999, Journal of the autonomic nervous system.

[24]  K. Bär,et al.  Non-linear complexity measures of heart rate variability in acute schizophrenia , 2007, Clinical Neurophysiology.

[25]  C. Hennekens,et al.  Schizophrenia and increased risks of cardiovascular disease. , 2005, American heart journal.

[26]  Clifford B. Saper,et al.  Subnuclear organization of the efferent connections of the parabrachial nucleus in the rat , 1984, Brain Research Reviews.

[27]  I. Homma,et al.  Breathing rhythms and emotions , 2008, Experimental physiology.

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

[29]  K. Bär,et al.  Gastric dysmotility in healthy first-degree relatives of patients with schizophrenia , 2010, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[30]  M. Tobin,et al.  A prospective study of indexes predicting the outcome of trials of weaning from mechanical ventilation. , 1992, The New England journal of medicine.

[31]  S A Shea,et al.  Behavioural and arousal‐related influences on breathing in humans , 1996, Experimental physiology.

[32]  Pere Caminal,et al.  Methods derived from nonlinear dynamics for analysing heart rate variability , 2009, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[33]  M. B. Ducharme,et al.  Study on the correlation of the autonomic nervous system responses to a stressor of high discomfort with personality traits , 2004, Physiology & Behavior.

[34]  D. Malaspina,et al.  Paternal age related schizophrenia and cardiac autonomic regulation profiles , 2011, Schizophrenia Research.

[35]  Andreas Voss,et al.  Differences between heart rate and blood pressure variability in schizophrenia , 2006, Biomedizinische Technik. Biomedical engineering.

[36]  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 .

[37]  H. Sauer,et al.  AUTONOMIC DYSFUNCTION IN UNAFFECTED FIRST-DEGREE RELATIVES OF PATIENTS SUFFERING FROM SCHIZOPHRENIA , 2010, Schizophrenia Research.

[38]  Giuseppe Baselli,et al.  Conditional entropy approach for the evaluation of the coupling strength , 1999, Biological Cybernetics.

[39]  M. Toichi,et al.  Influences of an Anticholinergic Antiparkinsonian Drug, Parkinsonism, and Psychotic Symptoms on Cardiac Autonomic Function in Schizophrenia , 2003, Journal of clinical psychopharmacology.

[40]  A. Malliani,et al.  Information domain analysis of cardiovascular variability signals: Evaluation of regularity, synchronisation and co-ordination , 2000, Medical and Biological Engineering and Computing.

[41]  Andreas Voss,et al.  The interaction between pupil function and cardiovascular regulation in patients with acute schizophrenia , 2008, Clinical Neurophysiology.

[42]  R. Jindal,et al.  Cardiac risk and schizophrenia. , 2005, Journal of psychiatry & neuroscience : JPN.

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

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

[45]  C. Wientjes,et al.  A comparison of three quantification methods for estimation of respiratory sinus arrhythmia. , 1990, Psychophysiology.

[46]  A Eberhard,et al.  Evaluation of respiratory inductive plethysmography: accuracy for analysis of respiratory waveforms. , 1997, Chest.

[47]  Frank H Wilhelm,et al.  The LifeShirt , 2003, Behavior modification.

[48]  Karl-Jürgen Bär,et al.  [Development of the "Mannheim Multicomponent Stress Test" (MMST)]. , 2010, Psychotherapie, Psychosomatik, medizinische Psychologie.

[49]  G. Wagner,et al.  Loss of efferent vagal activity in acute schizophrenia. , 2005, Journal of psychiatric research.

[50]  A. Voss,et al.  Joint symbolic dynamic analysis of beat-to-beat interactions of heart rate and systolic blood pressure in normal pregnancy , 2002, Medical and Biological Engineering and Computing.

[51]  A. Guz.  Brain, breathing and breathlessness. , 1997, Respiration physiology.

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

[53]  M. Kabir,et al.  Quantification of Cardiorespiratory Interactions Based on Joint Symbolic Dynamics , 2011, Annals of Biomedical Engineering.

[54]  Leanne M Williams,et al.  Dysregulation of arousal and amygdala-prefrontal systems in paranoid schizophrenia. , 2004, The American journal of psychiatry.

[55]  Tapas Pramanik,et al.  Immediate effect of slow pace bhastrika pranayama on blood pressure and heart rate. , 2009, Journal of alternative and complementary medicine.

[56]  Sandy Berger,et al.  Cardio-respiratory coupling indicates suppression of vagal activity in acute schizophrenia , 2009, Schizophrenia Research.

[57]  J. Mead,et al.  Measurement of the separate volume changes of rib cage and abdomen during breathing. , 1967, Journal of applied physiology.

[58]  Jan-Marino Ramirez,et al.  The neuronal mechanisms of respiratory rhythm generation , 1996, Current Opinion in Neurobiology.

[59]  P. Grossman.  The LifeShirt: a multi-function ambulatory system monitoring health, disease, and medical intervention in the real world. , 2004, Studies in health technology and informatics.

[60]  Sandy Berger,et al.  Influence of Age on Linear and Nonlinear Measures of Autonomic Cardiovascular Modulation , 2010, Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc.

[61]  K Miyoshi,et al.  The influence of psychotic states on the autonomic nervous system in schizophrenia. , 1998, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[62]  Alexander Glassman,et al.  Diminished cardiac vagal tone in schizophrenia: Associations to brain laterality and age of onset , 1997, Biological Psychiatry.

[63]  D. Malaspina,et al.  Nonlinear Complexity and Spectral Analyses of Heart Rate Variability in Medicated and Unmedicated Patients with Schizophrenia1 , 2005, Neuropsychobiology.

[64]  J. Karemaker,et al.  Influence of chemoreflexes on respiratory variability in healthy subjects. , 2002, American journal of respiratory and critical care medicine.