Skip to main content
    • Aa
    • Aa

Cardiac autonomic dysregulation in acute schizophrenia

  • Hsin-An Chang (a1), Chuan-Chia Chang (a1), Nian-Sheng Tzeng (a1), Terry B. J. Kuo (a2), Ru-Band Lu (a3) and San-Yuan Huang (a1)...

Altered cardiac autonomic function has been proposed in schizophrenia, but the results are mixed. Therefore, analyses with larger sample sizes and better methodology are needed.


To examine whether acute schizophrenia is associated with cardiac autonomic dysfunction, 314 unmedicated patients with acute schizophrenia and 409 healthy volunteers, aged 18–65 years, were recruited for a case–control analysis. The severity of schizophrenia symptoms was assessed with the Positive and Negative Syndrome Scale. Cardiac autonomic function was evaluated by measuring heart rate variability (HRV) parameters during the supine–standing–supine test. Frequency-domain indices of HRV were obtained.


Unmedicated patients with acute schizophrenia consistently exhibited reduced mean RR interval and HRV levels in a supine rest and standing position compared with healthy volunteers. The severity of psychopathology, in particular positive symptoms, was negatively correlated with cardiac vagal control.


These data suggest that acute schizophrenia is accompanied by cardiac autonomic dysregulation. In view of the higher risk for cardiac complications in these patients, one might also consider the antipsychotic treatment in favour of improving cardiac autonomic modulation. Further studies using larger patient groups and controlled therapeutics may better understand the influence of antipsychotic treatment on cardiac autonomic regulation in schizophrenia.

Corresponding author
San-Yuan Huang, Department of Psychiatry, Tri-Service General Hospital, No. 325, Cheng-Kung Road, Sec. 2, Nei-Hu District, Taipei 114, Taiwan, ROC. Tel: 011-886-2-8792-7220; Fax: 011-886-2-8792-7221; E-mail:
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

1. S Brown , H Inskip , B Barraclough . Causes of the excess mortality of schizophrenia. Br J Psychiatry 2000;177:212217.

2. CH Hennekens , AR Hennekens , D Hollar , DE Casey . Schizophrenia and increased risks of cardiovascular disease. Am Heart J 2005;150:11151121.

3. SM Curkendall , J Mo , DB Glasser , M Rose Stang , JK Jones . Cardiovascular disease in patients with schizophrenia in Saskatchewan, Canada. J Clin Psychiatry 2004;65:715720.

4. C Carpeggiani , M Emdin , F Bonaguidi et al. Personality traits and heart rate variability predict long-term cardiac mortality after myocardial infarction. Eur Heart J 2005;26:16121617.

5. LL Smith , M Kukielka , GE Billman . Heart rate recovery after exercise: a predictor of ventricular fibrillation susceptibility after myocardial infarction. Am J Physiol Heart Circ Physiol 2005;288:H1763H1769.

6.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. Circulation 1996;93:10431065.

7. S Boettger , D Hoyer , K Falkenhahn , M Kaatz , VK Yeragani , KJ Bar . Altered diurnal autonomic variation and reduced vagal information flow in acute schizophrenia. Clin Neurophysiol 2006;117:27152722.

8. J Galuszka , J Opavsky , J Lukl , P Stejskal , J Zapletalova , J Salinger . Short-term spectral analysis of heart rate variability during supine-standing-supine test in patients with paroxysmal atrial fibrillation. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2004;148:6367.

9. V Kojecky , J Bernatek , M Horowitz , S Zemek , J Bakala , A Hep . Prevalence and determinants of delayed gastric emptying in hospitalised type 2 diabetic patients. World J Gastroenterol 2008;14:15641569.

10. AJ Boulton , AI Vinik , JC Arezzo et al. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care 2005;28:956962.

11. T Okada , M Toichi , M Sakihama . Influences of an anticholinergic antiparkinsonian drug, parkinsonism, and psychotic symptoms on cardiac autonomic function in schizophrenia. J Clin Psychopharmacol 2003;23:441447.

12. M Toichi , Y Kubota , T Murai et al. The influence of psychotic states on the autonomic nervous system in schizophrenia. Int J Psychophysiol 1999;31:147154.

13. T Rechlin , D Claus , M Weis . Heart rate variability in schizophrenic patients and changes of autonomic heart rate parameters during treatment with clozapine. Biol Psychiatry 1994;35:888892.

14. H Cohen , MA Matar , Z Kaplan , M Kotler . Power spectral analysis of heart rate variability in psychiatry. Psychother Psychosom 1999;68:5966.

15. S Hennessy , WB Bilker , JS Knauss et al. Cardiac arrest and ventricular arrhythmia in patients taking antipsychotic drugs: cohort study using administrative data. BMJ 2002;325:1070.

16. A Birkhofer , J Geissendoerfer , P Alger et al. The deceleration capacity – a new measure of heart rate variability evaluated in patients with schizophrenia and antipsychotic treatment. Eur Psychiatry 2013;28:8186.

17. KP Su , WW Shen , CL Chuang , KP Chen , CC Chen . A pilot cross-over design study on QTc interval prolongation associated with sulpiride and haloperidol. Schizophr Res 2003;59:9394.

18. M Valkonen-Korhonen , MP Tarvainen , P Ranta-Aho et al. Heart rate variability in acute psychosis. Psychophysiology 2003;40:716726.

19. KJ Bär , A Letzsch , T Jochum , G Wagner , W Greiner , H Sauer . Loss of efferent vagal activity in acute schizophrenia. J Psychiatr Res 2005;39:519527.

21. HA Chang , RB Lu , MJ Shy , CC Chang , MS Lee , SY Huang . Brain-derived neurotrophic factor Val66Met polymorphism: association with psychopathological symptoms of schizophrenia? J Neuropsychiatry Clin Neurosci 2009;21:3037.

24. J Endicott , RL Spitzer . A diagnostic interview: the Schedule for Affective Disorders and Schizophrenia. Arch Gen Psychiatry 1978;35:837844.

25. SR Kay , A Fiszbein , LA Opler . The Positive And Negative Syndrome Scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261276.

27. CC Liu , TB Kuo , CC Yang . Effects of estrogen on gender-related autonomic differences in humans. Am J Physiol Heart Circ Physiol 2003;285:H2188H2193.

28. J Rottenberg . Cardiac vagal control in depression: a critical analysis. Biol Psychol 2007;74:200211.

29. Z Li , H Snieder , S Su et al. A longitudinal study in youth of heart rate variability at rest and in response to stress. Int J Psychophysiol 2009;73:212217.

30. LA Martin , JA Doster , JW Critelli et al. Ethnicity and type D personality as predictors of heart rate variability. Int J Psychophysiol 2010;76:118121.

31. MW Agelink , T Majewski , C Wurthmann et al. Effects of newer atypical antipsychotics on autonomic neurocardiac function: a comparison between amisulpride, olanzapine, sertindole, and clozapine. J Clin Psychopharmacol 2001;21:813.

32. JS Chang , CS Yoo , SH Yi et al. Changes in heart rate dynamics of patients with schizophrenia treated with risperidone. Prog Neuropsychopharmacol Biol Psychiatry 2010;34:924929.

33. KJ Bär , K Wernich , S Boettger et al. Relationship between cardiovagal modulation and psychotic state in patients with paranoid schizophrenia. Psychiatry Res 2008;157:255257.

34. D Malaspina , G Bruder , GW Dalack et al. Diminished cardiac vagal tone in schizophrenia: associations to brain laterality and age of onset. Biol Psychiatry 1997;41:612617.

37. JP Moak , DS Goldstein , BA Eldadah et al. Supine low-frequency power of heart rate variability reflects baroreflex function, not cardiac sympathetic innervation. Heart Rhythm 2007;4:15231529.

38. KJ Bar , M Koschke , S Berger et al. Influence of olanzapine on QT variability and complexity measures of heart rate in patients with schizophrenia. J Clin Psychopharmacol 2008;28:694698.

40. F Lombardi . Clinical implications of present physiological understanding of HRV components. Card Electrophysiol Rev 2002;6:245249.

41. M Mackowiak , D Dudys , A Chocyk , K Wedzony . Repeated risperidone treatment increases the expression of NCAM and PSA-NCAM protein in the rat medial prefrontal cortex. Eur Neuropsychopharmacol 2009;19:125137.

42. RK Mcnamara , JA Able , R Jandacek , T Rider , P TSO . Chronic risperidone treatment preferentially increases rat erythrocyte and prefrontal cortex omega-3 fatty acid composition: evidence for augmented biosynthesis. Schizophr Res 2009;107:150157.

43. RD Jindal , MS Keshavan , K Eklund , A Stevens , DM Montrose , VK Yeragani . Beat-to-beat heart rate and QT interval variability in first episode neuroleptic-naive psychosis. Schizophr Res 2009;113:176180.

44. LM Williams , P Das , AW Harris et al. Dysregulation of arousal and amygdala-prefrontal systems in paranoid schizophrenia. Am J Psychiatry 2004;161:480489.

45. SW Wong , N Masse , DS Kimmerly , RS Menon , JK Shoemaker . Ventral medial prefrontal cortex and cardiovagal control in conscious humans. Neuroimage 2007;35:698708.

46. G Ziegler , R Dahnke , VK Yeragani , KJ Bar . The relation of ventromedial prefrontal cortex activity and heart rate fluctuations at rest. Eur J Neurosci 2009;30:22052210.

47. J Jenkins , PM Shajahan , JM Lappin , KP Ebmeier . Right and left prefrontal transcranial magnetic stimulation at 1 Hz does not affect mood in healthy volunteers. BMC Psychiatry 2002;2:1.

48. N Grossheinrich , A Rau , O Pogarell et al. Theta burst stimulation of the prefrontal cortex: safety and impact on cognition, mood, and resting electroencephalogram. Biol Psychiatry 2009;65:778784.

49. L Appleby , S Thomas , N Ferrier , G Lewis , J Shaw , T Amos . Sudden unexplained death in psychiatric in-patients. Br J Psychiatry 2000;176:405406.

50. WA Ray , CP Chung , KT Murray , K Hall , CM Stein . Atypical antipsychotic drugs and the risk of sudden cardiac death. N Engl J Med 2009;360:225235.

51. H Cohen , U Loewenthal , M Matar , M Kotler . Association of autonomic dysfunction and clozapine. Heart rate variability and risk for sudden death in patients with schizophrenia on long-term psychotropic medication. Br J Psychiatry 2001;179:167171.

52. B Silke , C Campbell , DJ King . The potential cardiotoxicity of antipsychotic drugs as assessed by heart rate variability. J Psychopharmacol 2002;16:355360.

53. YC Wang , CC Yang , YM Bai , TB Kuo . Heart rate variability in schizophrenic patients switched from typical antipsychotic agents to amisulpride and olanzapine. 3-month follow-up. Neuropsychobiology 2008;57:200205.

54. KJ Bar , MK Boettger , M Koschke et al. Non-linear complexity measures of heart rate variability in acute schizophrenia. Clin Neurophysiol 2007;118:20092015.

55. KJ Bar , MK Boettger , S Schulz et al. The interaction between pupil function and cardiovascular regulation in patients with acute schizophrenia. Clin Neurophysiol 2008;119:22092213.

56. N Sato , S Miyake , J Akatsu , M Kumashiro . Power spectral analysis of heart rate variability in healthy young women during the normal menstrual cycle. Psychosom Med 1995;57:331335.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Acta Neuropsychiatrica
  • ISSN: 0924-2708
  • EISSN: 1601-5215
  • URL: /core/journals/acta-neuropsychiatrica
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 1
Total number of PDF views: 10 *
Loading metrics...

Abstract views

Total abstract views: 199 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 24th May 2017. This data will be updated every 24 hours.