Вариабельность сердечного ритма при шизофрении и шизоаффективном расстройстве

Цель обзора: анализ и систематизация результатов научных работ по изучению вариабельности сердечного ритма при шизофрении и шизоаффективном расстройстве.

Основные положения. В многочисленных исследованиях продемонстрировано снижение показателей общей вариабельности сердечного ритма и интенсивности вагусных влияний у больных шизофренией и шизоаффективным расстройством, в том числе в ответ на когнитивную или стрессовую нагрузку. У них также выявлено уменьшение барорефлекторной чувствительности. Эти нарушения наблюдаются у пациентов, ранее не получавших медикаментозное лечение, и у здоровых родственников первой линии родства. Их выраженность взаимосвязана с тяжестью продуктивной, негативной и аффективной симптоматики, а также с наличием метаболического синдрома. В психотических состояниях вегетативная кардиальная дизрегуляция выражена сильнее. Антипсихотики с М-холинолитической и/или α₁ -адренолитической активностью могут ее усугублять. Указанные нарушения выявляются не только при шизофрении, но и при других психических и соматических расстройствах, в патогенезе которых участвует дистресс.

Заключение. Возможность применения показателей вариабельности сердечного ритма в качестве дополнительных критериев оценки тяжести психоза, прогноза эффективности терапии, а также для ранней стратификации кардиоваскулярных рисков требует дальнейшего изучения в научных исследованиях.

1. Kraepelin E. Psychiatry: а textbook for students and physicians. Canton, MA: Watson Publishing International; 1899/1990.

2. Hattori S., Suda A., Kishida I., Miyauchi M. et al. Association between dysfunction of autonomic nervous system activity and mortality in schizophrenia. Compr. Psychiatry. 2018; 86: 119–22. DOI: 10.1016/j.comppsych.2018.08.002

3. Hennekens C.H., Hennekens A.R., Hollar D., Casey D.E. Schizophrenia and increased risks of cardiovascular disease. Am. Heart J. 2005; 150(6): 1115–21. DOI: 10.1016/j.ahj.2005.02.007

4. Loas G., Azi A., Noisette C., Yon V. Mortality among chronic schizophrenic patients: a prospective 14-year follow-up study of 150 schizophrenic patients. Encephale. 2008; 34(1): 54–60. DOI: 10.1016/j.encep.2007.07.005

5. Ringen P.A., Engh J.A., Birkenaes A.B., Dieset I. et al. Increased mortality in schizophrenia due to cardiovascular disease — nonsystematic review of epidemiology, possible causes, and interventions. Front. Psychiatry. 2014; 5: 137. DOI: 10.3389/fpsyt.2014.00137

6. Manu P., Kane J.M., Correll C.U. Sudden deaths in psychiatric patients. J. Clin. Psychiatry. 2011; 72(7): 936–41. DOI: 10.4088/JCP.10m06244gry

7. Beary M., Hodgson R., Wildgust H.J. A critical review of major mortality risk factors for all-cause mortality in first-episode schizophrenia: clinical and research implications. J. Psychopharmacol. 2012; 26(5 suppl.): 52–61. DOI: 10.1177/0269881112440512

8. Бокерия Л.А., Бокерия О.Л., Волковская И.В. Вариабельность сердечного ритма: методы измерения, интерпретация, клиническое использование. Анналы аритмологии. 2009; 6(4): 21–32.

9. 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(5): 1043–65.

10. Баевский Р.М., Иванов Г.Г., Чирейкин Л.В., Гаврилушкин А.П. и др. Анализ вариабельности сердечного ритма при использовании различных электрокардиографических систем: методические рекомендации. Ижевск: изд-во Удмуртского ун-та; 2003: 201– 55.

11. Liu Y., Huang Y., Zhou J., Li G. et al. Altered heart rate variability in patients with schizophrenia during an autonomic nervous test. Front. Psychiatry. 2021; 30(12): 626991. DOI: 10.3389/fpsyt.2021.626991

12. Chang J.S., Yoo C.S., Yi S.H., Hong K.H. et al. Differential pattern of heart rate variability in patients with schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2009; 33(6): 991–5. DOI: 10.1016/j.pnpbp.2009.05.004

13. Mujica-Parodi L.R., Yeragani V., Malaspina D. Nonlinear complexity and spectral analyses of heart rate variability in medicated and unmedicated patients with schizophrenia. Neuropsychobiology. 2005; 51(1): 10–15. DOI: 10.1159/000082850

14. Clamor A., Lincoln T.M., Thayer J.F., Koenig J. Resting vagal activity in schizophrenia: meta-analysis of heart rate variability as a potential endophenotype. Br. J. Psychiatry. 2016; 208(1): 9–16. DOI: 10.1192/bjp.bp.114.160762

15. Montaquila J.M., Trachik B.J., Bedwell J.S. Heart rate variability and vagal tone in schizophrenia: a review. J. Psychiatr. Res. 2015; 69: 57–66. DOI: 10.1016/j.jpsychires.2015.07.025

16. Bär K.-J., Wernich K., Boettger S., Cordes J. et al., Relationship between cardiovagal modulation and psychotic state in patients with paranoid schizophrenia. Psych. Res. 2008; 157(1–3): 255–7. DOI: 10.1016/j.psychres.2007.04.021

17. Boettger S., Hoyer D., Falkenhahn K., Kaatz M. et al. Altered diurnal autonomic variation and reduced vagal information flow in acute schizophrenia. Clin. Neurophysiol. 2006; 117(12): 2715–22. DOI: 10.1016/j.clinph.2006.08.009

18. Birkhofer A., Geissendoerfer J., Alger P., Mueller A. et al. The deceleration capacity — a new measure of heart rate variability evaluated in patients with schizophrenia and antipsychotic treatment. Eur. J. Psychiatry. 2013; 28(2): 81–6. DOI: 10.1159/000452770

19. Thayer J.F., Lane R.D. A model of neurovisceral integration in emotion regulation and dysregulation. J. Affect. Disord. 2000; 61(3): 201–16. DOI: 10.1016/s0165-0327(00)00338-4

20. Akar S.A., Kara S., Latifoğlu F., Bilgiç V. Analysis of heart rate variability during auditory stimulation periods in patients with schizophrenia. J. Clin. Monit. Comput. 2015; 29(1): 153–62. DOI: 10.1007/s10877-014-9580-8

21. Bär K.-J., Letzsch A., Jochum T., Wagner G. et al. Loss of efferent vagal activity in acute schizophrenia. J. Psychiatr. Res. 2005; 39(5): 519–27. DOI: 10.1016/j.jpsychires.2004.12.007

22. Fujibayashi M., Matsumoto T., Kishida I., Kimura T. et al. Autonomic nervous system activity and psychiatric severity in schizophrenia. Psychiatry Clin. Neurosci. 2009; 63(4): 538–45. DOI: 10.1111/j.1440-1819.2009.01983.x

23. Ieda M., Miyaoka T., Wake R., Liaury K. et al. Evaluation of autonomic nervous system by salivary alpha-amylase level and heart rate variability in patients with schizophrenia. Eur. Arch. Psychiatry Clin. Neurosci. 2014; 264(1): 83–7. DOI: 10.1007/s00406-013-0411-6

24. Moon E., Lee S.H., Kim D.H., Hwang B. Comparative study of heart rate variability in patients with schizophrenia, bipolar disorder, post-traumatic stress disorder, or major depressive disorder. Clin. Psychopharmacol. Neurosci. 2013; 11(3): 137–43. DOI: 10.9758/cpn.2013.11.3.137

25. Iwamoto Y., Kawanishi C., Kishida I., Furuno T. et al. Dose-dependent effect of antipsychotic drugs on autonomic nervous system activity in schizophrenia. BMC Psychiatry. 2012; 12: 199. DOI: 10.1186/1471-244X-12-199

26. Schulz S., Bolz M., Bär K.-J, Voss A. Central and autonomic nervous system coupling in schizophrenia. Philos. Trans. A Math. Phys. Eng. Sci. 2016; 374(2067): 20150178. DOI: 10.1098/rsta.2015.0178

27. Guccione C., Di Scalea G.L., Ambrosecchia M., Terrone G. et al. Early signs of schizophrenia and autonomic nervous system dysregulation: a literature review. Clin. Neuropsychiatry. 2019; 16(2): 86–97.

28. Bär K.-J. Cardiac autonomic dysfunction in patients with schizophrenia and their healthy relatives — a small review. Front. Neurol. 2015; 6: 139. DOI: 10.3389/fneur.2015.00139

29. Bär K.-J., Boettger M.K., Berger S., Baier V. et al. Decreased baroreflex sensitivity in acute schizophrenia. J. Appl. Physiol. 2007; 102(3): 1051–6. DOI: 10.1152/japplphysiol.00811.2006

30. Kudat H., Akkaya V., Sozen A.B., Salman S. et al. Heart rate variability in diabetes patients. J. Int. Med. Res. 2006; 34(3): 291–6. DOI: 10.1177/147323000603400308

31. Haigh S.M., Walford T.P., Brosseau P. Heart rate variability in schizophrenia and autism. Front. Psychyatry, 2021; 12: 760396. DOI: 10.3389/fpsyt.2021.760396

32. Bengtsson J., Olsson E., Igelström H., Persson J. et al. Ambulatory heart rate variability in schizophrenia or depression: impact of anticholinergic burden and other factors. J. Clin. Psychopharmacol. 2021; 41(2): 121–8. DOI: 10.1097/JCP.0000000000001356

33. Антипова О.С. Проблемы и перспективы изучения вегетативной регуляции при депрессиях. Доктор.Ру. 2019; 6(161): 42–6. DOI: 10.31550/1727-2378-2019-161-6-42-46

34. Beauchaine T.P., Thayer J.F. Heart rate variability as a transdiagnostic biomarker of psychopathology. Int. J. Psychophysiol. 2015; 98(2 Pt2): 338–50. DOI: 10.1016/j.ijpsycho.2015.08.004

35. Davydov D.M., Shapiro D., Cook I.A., Goldstein I. Baroreflex mechanisms in major depression. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2007; 31(1): 164–77. DOI: 10.1016/j.pnpbp.2006.08.015

36. Holzman J.B., Bridgett D.J. Heart rate variability indices as biomarkers of top-down self-regulatory mechanisms: a metaanalytic review. Neurosci. Biobehav. Rev. 2017; 74 (PtA): 233–55. DOI: 10.1016/j.neubiorev.2016.12.032

37. La Rovere M.T., Bigger J.T. Jr, Marcus F.I., Mortara A. et al. Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) Investigators. Lancet. 1998; 351(9101): 478–84. DOI: 10.1016/s0140-6736(97)11144-8

38. La Rovere M.T., Pinna G.D., Hohnloser S.H., Marcus F.I. et al. Baroreflex sensitivity and heart rate variability in the identification of patients at risk for life-threatening arrhythmias: implications for clinical trials. Circulation. 2001; 103(16): 2072–7. DOI: 10.1161/01.cir.103.16.2072

39. Thayer J.F., Ahs F., Fredrikson M., Sollers J.J. 3rd et al. A metaanalysis of heart rate variability and neuroimaging studies: implications for heart rate variability as a marker of stress and health. Neurosci. Biobehav. Rev. 2012; 36(2): 747–56. DOI: 10.1016/j.neubiorev.2011.11.009

40. Bär K.-J., Berger S., Metzner M., Boettger M.K. et al. Autonomic dysfunction in unaffected first-degree relatives of patients suffering from schizophrenia. Schizophr. Bull. 2009; 36(5): 1050–8. DOI: 10.1093/schbul/sbp024

41. Valkonen-Korhonen M., Tarvainen M.P., Ranta-Aho P., Karjalainen P.A. et al. Heart rate variability in acute psychosis. Psychophysiology. 2003; 40(5): 716–26. DOI: 10.1111/1469-8986.00072

42. Hempel R.J., Tulen J.H., van Beveren N.J., van Steenis H.G. et al. Physiological responsivity to emotional pictures in schizophrenia. J. Psychiatr. Res. 2005; 39(5): 509–18. DOI: 10.1016/j.jpsychires.2004.11.004

43. Castro M.N., Vigo D.E., Weidema H., Fahrer R.D. et al. Heart rate variability response to mental arithmetic stress in patients with schizophrenia. Autonomic response to stress in schizophrenia. Schizophr. Res. 2008; 99(1–3): 294–303. DOI: 10.1016/j.schres.2007.08.025

44. Reed A.C., Lee J., Green M.F., Hamilton H.K. et al. Associations between physiological responses to social-evaluative stress and daily functioning in first-episode schizophrenia. Schizophr. Res. 2020; 218: 233–9. DOI: 10.1016/j.schres.2019.12.040

45. Khandoker A.H., Fujibayashi M., Moritani T., Palaniswami M. Assessing sympatho-vagal balance in schizophrenia through toneentropy analysis. Comp. Cardiol. 2010; 37: 69–72.

46. Benjamin B.R., Valstad M., Elvsåshagen T., Jönsson E.G. et al. Heart rate variability is associated with disease severity in psychosis spectrum disorders. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2021; 111: 110108. DOI: 10.1016/j.pnpbp.2020.110108

47. Chang H.A., Chang C.C., Tzeng N.S., Kuo T.B. et al. Cardiac autonomic dysregulation in acute schizophrenia. Acta Neuropsychiatr. 2013; 25(3): 155–64. DOI: 10.1111/acn.12014

48. Kim J.-H., Ann J.-H., Lee J. Relationship between heart rate variability and the severity of psychotic symptoms in schizophrenia. Acta Neuropsychiatr. 2011; 23(4): 161–6. DOI: 10.1111/j.1601-5215.2011.00549.x

49. Huang W.C., Liu W.S., Chen T.T., Chen W.H. et al. Parasympathetic activity as a potential biomarker of negative symptoms in patients with schizophrenia. Asia Pac. Psychiatry. 2020; 12(3): e12392. DOI: 10.1111/appy.12392

50. Peupelmann J., Boettger M.K., Ruhland C., Berger S. et al. Cardiorespiratory coupling indicates suppression of vagal activity in acute schizophrenia. Schizophr. Res. 2009; 112(1–3): 153–7. DOI: 10.1016/j.schres.2009.03.042

51. Henry B.L., Minassian A., Paulus M.P., Geyer M.A. et al. Heart rate variability in bipolar mania and schizophrenia. J. Psychiatr. Res. 2010; 44(3): 168–76. DOI: 10.1016/j.jpsychires.2009.07.011

52. Quintana D., Westlye L., Kaufmann T., Rustan O. et al. Reduced heart rate variability in schizophrenia and bipolar disorder compared to healthy controls. Acta Psychiatr. Scand. 2015; 133(1): 44–52. DOI: 10.1111/acps.12498

53. Mathewson K.J., Jetha M.K., Goldberg J.O., Schmidt L.A. Autonomic regulation predicts performance on Wisconsin Card Sorting Test (WCST) in adults with schizophrenia. Biol. Psychol. 2012; 91(3): 389–99. DOI: 10.1016/j.biopsycho.2012.09.002

54. Kimhy D., Wall M.M., Hansen M.C., Vakhrusheva J. et al. Autonomic regulation and auditory hallucinations in individuals with schizophrenia: an experience sampling study. Schizophr. Bull. 2017; 43(4): 754–63. DOI: 10.1093/schbul/sbw219

55. Резников М.К., Ширяев О.Ю., Житкова С.Н. Взаимосвязь психофармакотерапии и вариабельности сердечного ритма больных шизофренией. Журнал научных статей. Здоровье и образование в XXI веке. Материалы VIII Международного конгресса «Здоровье и образование в XXI веке; концепции болезней цивилизации». 2007; 9(2): 165.

56. Zhang T.H., Tang X.C., Xu L.H., Wei Y.Y. at al. Imbalance model of heart rate variability and pulse wave velocity in psychotic and nonpsychotic disorders. Schizophr. Bull. 2022. 48(1): 154–65. DOI: 10.1093/schbul/sbab080

57. Yuen J.W.Y., Kim D.D., Procyshyn R.M., White R.F. et al. Clozapineinduced cardiovascular side effects and autonomic dysfunction: a systematic review. Front. Neurosci. 2018; 12: 203. DOI: 10.3389/fnins.2018.00203

58. Agelink M.W., Majewski T., Wurthmann C., Lukas K. et al. Effects of newer atypical antipsychotics on autonomic neurocardiac function: a сomparison between amisulpride, olanzapine, sertindole, and clozapine. J. Clin. Psychopharmacol. 2001; 21(1): 8–13. DOI: 10.1097/00004714-200102000-00003

59. Penttilä J., Kuusela T., Scheinin H. Analysis of rapid heart rate variability in the assessment of anticholinergic drug effects in humans. Eur. J. Clin. Pharm. 2005; 61(8): 559–65. DOI: 10.1007/s00228-005-0953-2

60. Cohen H., Loewenthal U., Matar M., Kotler M. 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: 167–71. DOI: 10.1192/bjp.179.2.167

61. Wang Y.C., Yang C.C., Bai Y.M., Kuo T.B. Heart rate variability in schizophrenic patients switched from typical antipsychotic agents to amisulpride and olanzapine. 3-month follow-up. Neuropsychobiology. 2008; 57(4): 200–5. DOI: 10.1159/000149818

62. Hattori S., Kishida I., Suda A., Miyauchi M. et al. Effects of four atypical antipsychotics on autonomic nervous system activity in schizophrenia. Schizophr. Res. 2018; 193: 134–8. DOI: 10.1016/j. schres.2017.07.004

63. Lee K., Park J., Choi J., Park C.G. Heart rate variability and metabolic syndrome in hospitalized patients with schizophrenia. J. Korean Acad. Nurs. 2011; 41(6): 788–94. DOI: 10.4040/jkan.2011.41.6.788

64. Kim J.A., Park Y.G., Cho K.H., Hong M.H. et al. Heart rate variability and obesity indices: emphasis on the response to noise and standing. J. Am. Board Fam. Med. 2005; 18(2): 97–103. DOI: 10.3122/jabfm.18.2.97

65. McEvoy J.P., Meyer J.M., Goff D.C., Nasrallah H.A. et al. Prevalence of the metabolic syndrome in patients with schizophrenia: Baseline results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial and comparison with national estimates from NHANES III. Schizophr. Res. 2005; 80(1): 19–32. DOI: 10.1016/j.schres.2005.07.014

66. Meyer J.M., Nasrallah H.A., McEvoy J.P., Goff D.C. et al. The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia trial: clinical comparison of subgroups with and without the metabolic syndrome. Schizophr. Res. 2005; 80(1): 9–18. DOI: 10.1016/j.schres.2005.07.015

67. Stogios N., Gdanski A., Gerretsen P., Chintoh A.F. et al. Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health. NPJ Schizophr. 2021; 7(1): 22. DOI: 10.1038/s41537-021-00151-6

68. Hsu C.C., Liang C.S., Tai Y.M., Cheng S.L. Incongruent changes in heart rate variability and body weight after discontinuing aerobic exercise in patients with schizophrenia. Int. J. Psychophysiol. 2016; 109: 132–7. DOI: 10.1016/j.ijpsycho.2016.08.011