Autism spectrum disorder (ASD) represents a serious neurodevelopmental disorder associated with autonomic nervous system dysregulation. The aim was to study complex cardiovascular autonomic regulation using heart rate variability (HRV) and systolic blood pressure variability (SBPV) linear/non-linear analysis at rest and during orthostasis, and to assess plasma levels of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) in autistic children. Twenty-five ASD boys and 25 age and gender-matched children at the age 7-15 years were examined. After venous blood taking, continuous ECG and blood pressure biosignals were recorded at rest and during orthostasis. Evaluated parameters: RR intervals, high- and low-frequency band of HRV spectral analysis (HF-HRV, LF-HRV), symbolic dynamics parameters 0V%, 1V%, 2LV%, 2UV%, low- and high-frequency band of SBPV (LF-SBPV, HF-SBPV), systolic, diastolic, mean blood pressure, EGF, VEGF plasma levels. RR intervals were significantly shortened and the HF-HRV, LF-SBPV, HF-SBPV parameters were significantly lower at rest, the HF-HRV and LF-SBPV remained lower during orthostasis in autistic children compared to controls (p<0.05). EGF plasma levels were significantly lower in ASD compared to controls (p=0.046). No significant differences were found in remaining parameters. Our study revealed tachycardia, cardiovagal underactivity, and blunted sympathetic vasomotor regulation at rest and during orthostasis in autistic children. Additionally, complex heart rate dynamics are similar in autistic children than controls. Furthermore, EGF was reduced in autistic children without significant correlations with any autonomic parameters. We suggest that the abnormal complex cardiovascular reflex control could contribute to understanding the pathway linking autonomic features and autism.

Biomedical Center Martin JFM CU Mala Hora Martin Slovak Republic

Zobrazit více v PubMed

AJRAM LA, HORDER J, MENDEZ MA, GALANOPOULOS A, BRENNAN LP, WICHERS RH, ROBERTSON DM, MURPHY CM, ZINKSTOK J, IVIN G, HEASMAN M, MEEK D, TRICKLEBANK MD, BARKER GJ, LYTHGOE DJ, EDDEN RAE, WILLIAMS SC, MURPHY DGM, MCALONAN GM. Shifting brain inhibitory balance and connectivity of the prefrontal cortex of adults with autism spectrum disorder. Transl Psychiatry. 2017;7:e1137. doi: 10.1038/tp.2017.104. PubMed DOI PMC

ATTIA ZI, KAPA S, YAO X, LOPEZ-JIMENEZ F, MOHAN TL, PELLIKKA PA, CARTER RE, SHAH ND, FRIEDMAN PA, NOSEWORTHY PA. Prospective validation of a deep learning electrocardiogram algorithm for the detection of left ventricular systolic dysfunction. J Cardiovasc Electrophysiol. 2019;30:668–674. doi: 10.1111/jce.13889. PubMed DOI

BABINSKA K, BUCOVA M, DURMANOVA V, LAKATOSOVA S, JANOSIKOVA D, BAKOS J, HLAVATA A, OSTATNIKOVA D. Increased plasma levels of the high mobility group box 1 protein (HMGB1) are associated with a higher score of gastrointestinal dysfunction in individuals with autism. Physiol Res. 2014;63:613–618. doi: 10.33549/physiolres.932932. PubMed DOI

BAILON R, SORNMO L, LAGUNA P. A robust method for ECG-based estimation of the respiratory frequency during stress testing. IEEE Trans Biomed Eng. 2006;53:1273–1285. doi: 10.1109/TBME.2006.871888. PubMed DOI

BENARROCH EE. The Central autonomic network: functional organization, dysfunction, and perspective. Mayo Clin Proc. 1993;68:988–1001. doi: 10.1016/S0025-6196(12)62272-1. PubMed DOI

BENEVIDES TW, LANE SJ. A review of cardiac autonomic measures: considerations for examination of physiological response in children with autism spectrum disorder. J Autism Dev Disord. 2015;45:560–575. doi: 10.1007/s10803-013-1971-z. PubMed DOI

BOARDMAN A, SCHLINDWEIN FS, ROCHA AP, LEITE A. A study on the optimum order of autoregressive models for heart rate variability. Physiol Meas. 2002;23:325–336. doi: 10.1088/0967-3334/23/2/308. PubMed DOI

BRICOUT VA, PACE M, DUMORTIER L, FAVRE-JUVIN A, GUINOT M. Autonomic responses to head-up tilt test in children with autism spectrum disorders. J Abnorm Child Psychol. 2018;46:1121–1128. doi: 10.1007/s10802-017-0339-9. PubMed DOI

BUJNAKOVA I, ONDREJKA I, MESTANIK M, VISNOVCOVA Z, MESTANIKOVA A, HRTANEK I, FLESKOVA D, CALKOVSKA A, TONHAJZEROVA I. Autism spectrum disorder is associated with autonomic underarousal. Physiol Res. 2016;65:673–682. doi: 10.33549/physiolres.933528. PubMed DOI

CHENG YC, HUANG YC, HUANG WL. Heart rate variability in individuals with autism spectrum disorders: A meta-analysis. Neurosci Biobehav Rev. 2020;118:463–471. doi: 10.1016/j.neubiorev.2020.08.007. PubMed DOI

COLE TJ, LOBSTEIN T. Extended international (IOTF) body mass index cut-offs for thinness, overweight and obesity. Pediatr Obes. 2012;7:284–294. doi: 10.1111/j.2047-6310.2012.00064.x. PubMed DOI

DAHLMAN AS, BLENNOW K, ZETTERBERG H, GLISE K, JONSDOTTIR IH. Growth factors and neurotrophins in patients with stress-related exhaustion disorder. Psychoneuroendocrinology. 2019;109:104415. doi: 10.1016/j.psyneuen.2019.104415. PubMed DOI

ELECTROPHYSIOLOGY T F OF THE E S. Heart Rate Variability. Circulation. 1996;93:1043–1065. doi: 10.1161/01.CIR.93.5.1043. PubMed DOI

ELLENBROEK B, SENGUL H. Autism spectrum disorders: Autonomic alterations with a special focus on the heart. Hear Mind. 2017;1:78. doi: 10.4103/hm.hm_5_17. DOI

ESHRAGHI RS, DAVIES C, IYENGAR R, PEREZ L, MITTAL R, ESHRAGHI AA. Gut-induced inflammation during development may compromise the blood-brain barrier and predispose to autism spectrum disorder. J Clin Med. 2020;10:27. doi: 10.3390/jcm10010027. PubMed DOI PMC

FABER J, TUHACEK M, MESTAN J. Synchronization of EEG activity and respiration. Cesk Neurol. 1970;33:296–301. PubMed

GALVEZ-CONTRERAS AY, CAMPOS-ORDONEZ T, GONZALEZ-CASTANEDA RE, GONZALEZ-PEREZ O. Alterations of growth factors in autism and attention-deficit/hyperactivity disorder. Front Psychiatry. 2017;8:126. doi: 10.3389/fpsyt.2017.00126. PubMed DOI PMC

GOLDSTEIN DS, BENTHO O, PARK MY, SHARABI Y. Low-frequency power of heart rate variability is not a measure of cardiac sympathetic tone but may be a measure of modulation of cardiac autonomic outflows by baroreflexes. Exp Physiol. 2011;96:1255–1261. doi: 10.1113/expphysiol.2010.056259. PubMed DOI PMC

GOODMAN B. Autonomic dysfunction in autism spectrum disorders (ASD) (P5 17) Neurology. 2016;86

GUO X, DOMINICK KC, MINAI AA, LI H, ERICKSON CA, LU LJ. Diagnosing autism spectrum disorder from brain resting-state functional connectivity patterns using a deep neural network with a novel feature selection method. Front Neurosci. 2017;11:460. doi: 10.3389/fnins.2017.00460. PubMed DOI PMC

HANNUN AY, RAJPURKAR P, HAGHPANAHI M, TISON GH, BOURN C, TUZRAKHIA MP, NG AY. Cardiologist-level arrhythmia detection and classification in ambulatory electrocardiograms using a deep neural network. Nat Med. 2019;25:65–69. doi: 10.1038/s41591-018-0268-3. PubMed DOI PMC

HAYANO J, YUDA E. Pitfalls of assessment of autonomic function by heart rate variability. J Physiol Anthropol. 2019;38 doi: 10.1186/s40101-019-0193-2. PubMed DOI PMC

KASAHARA Y, YOSHIDA C, NAKANISHI K, FUKASE M, SUZUKI A, KIMURA Y. Alterations in the autonomic nerve activities of prenatal autism model mice treated with valproic acid at different developmental stages. Sci Rep. 2020;10:1–13. doi: 10.1038/s41598-020-74662-0. PubMed DOI PMC

LORY C, KADLASKAR G, MCNALLY KEEHN R, FRANCIS AL, KEEHN B. Brief report: Reduced heart rate variability in children with autism spectrum disorder. J Autism Dev Disord. 2020;50:4183–4190. doi: 10.1007/s10803-020-04458-8. PubMed DOI PMC

MACOVA L, BICIKOVA M, OSTATNIKOVA D, HILL M, STARKA L. Vitamin D, neurosteroids and autism. Physiol Res. 2017;66:333–340. doi: 10.33549/physiolres.933721. PubMed DOI

MAGNON C. Role of the autonomic nervous system in tumorigenesis and metastasis. Mol Cell Oncol. 2015;2:e975643. doi: 10.4161/23723556.2014.975643. PubMed DOI PMC

MCCRATY R, SHAFFER F. Heart rate variability: New perspectives on physiological mechanisms, assessment of self-regulatory capacity, and health risk. Glob Adv Heal Med. 2015;4:46–61. doi: 10.7453/gahmj.2014.073. PubMed DOI PMC

MESTANIK M, MESTANIKOVA A, VISNOVCOVA Z, CALKOVSKA A, TONHAJZEROVA I. Cardiovascular sympathetic arousal in response to different mental stressors. Physiol Res. 2015;64:585–594. doi: 10.33549/physiolres.933217. PubMed DOI

MUSCATELLO RA, VANDEKAR SN, CORBETT BA. Evidence for decreased parasympathetic response to a novel peer interaction in older children with autism spectrum disorder: a case-control study. J Neurodev Disord. 2021;13 doi: 10.1186/s11689-020-09354-x. PubMed DOI PMC

OSTATNIKOVA D, KUBRANSKA A, MARCINCAKOVA V, PIVOVARCIOVA A, BABKOVA-DURDIAKOVA J. Neuroendocrine contribution to autism etiology. Act Nerv Super Rediviva. 2016;58:65–68.

OSTATNIKOVA D, LAKATOSOVA S, BABKOVA J, HODOSY J, CELEC P. Testosterone and the brain: from cognition to autism. Physiol Res. 2020;69:403–419. doi: 10.33549/10.33549/physiolres.934592. PubMed DOI PMC

PAGANI M, LOMBARDI F, GUZZETTI S, RIMOLDI O, FURLAN R, PIZZINELLI P, SANDRONE G, MALFATTO G, DELL’ORTO S, PICCALUGA E. Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog. Circ Res. 1986;59:178–193. doi: 10.1161/01.RES.59.2.178. PubMed DOI

PARK G, THAYER JF. From the heart to the mind: cardiac vagal tone modulates top-down and bottom-up visual perception and attention to emotional stimuli. Front Psychol. 2014;5:278. doi: 10.3389/fpsyg.2014.00278. PubMed DOI PMC

PATRIQUIN MA, HARTWIG EM, FRIEDMAN BH, PORGES SW, SCARPA A. Autonomic response in autism spectrum disorder: Relationship to social and cognitive functioning. Biol Psychol. 2019;145:185–197. doi: 10.1016/j.biopsycho.2019.05.004. PubMed DOI

PORGES SW, MACELLAIO M, STANFILL SD, MCCUE K, LEWIS GF, HARDEN ER, HANDELMAN M, DENVER J, BAZHENOVA OV, HEILMAN KJ. Respiratory sinus arrhythmia and auditory processing in autism: Modifiable deficits of an integrated social engagement system? Int J Psychophysiol. 2013;88:261–270. doi: 10.1016/j.ijpsycho.2012.11.009. PubMed DOI PMC

PORTA A, TOBALDINI E, GUZZETTI S, FURLAN R, MONTANO N, GNECCHI-RUSCONE T. Assessment of cardiac autonomic modulation during graded head-up tilt by symbolic analysis of heart rate variability. Am J Physiol Hear Circ Physiol. 2007;293:702–708. doi: 10.1152/ajpheart.00006.2007. PubMed DOI

SHAFFER F, GINSBERG JP. An overview of heart rate variability metrics and norms. Front Public Health. 2017;5:258. PubMed PMC

SILVA LEV, GERALDINI VR, DE OLIVEIRA BP, SILVA CAA, PORTA A, FAZAN R. Comparison between spectral analysis and symbolic dynamics for heart rate variability analysis in the rat. Sci Rep. 2017;7 doi: 10.1038/s41598-017-08888-w. PubMed DOI PMC

SKOBRTAL P, BAZINKOVA E, CHALUPOVA M. The possibilities of using a stress profile in psychotherapy. Cognitive Remediation Journal. 2021;10:11–13.

SONG R, LIU J, KONG X. Autonomic dysfunction and autism: subtypes and clinical perspectives. N A J Med Sci. 2016;9:172–180. doi: 10.5507/crj.2021.002. DOI

STAUSS HM. Idetification of blood pressure control mechanisms by power spectral analysis. Clin Exp Pharmacol Physiol. 2007;34:362–368. doi: 10.1111/j.1440-1681.2007.04588.x. PubMed DOI

STONER R, CHOW ML, BOYLE MP, SUNKIN SM, MOUTON PR, ROY S, WYNSHAW-BORIS A, COLAMARINO SA, LEIN ES, COURCHESNE E. Patches of disorganization in the neocortex of children with autism. N Engl J Med. 2014;370:1209–1219. doi: 10.1056/NEJMoa1307491. PubMed DOI PMC

TARVAINEN MP, RANTA-AHO PO, KARJALAINEN PA. An advanced detrending method with application to HRV analysis. IEEE Trans Biomed Eng. 2002;49:172–175. doi: 10.1109/10.979357. PubMed DOI

TAYLOR EC, LIVINGSTON LA, CALLAN MJ, ASHWIN C, SHAH P. Autonomic dysfunction in autism: The roles of anxiety, depression, and stress. Autism. 2021;25:744–752. doi: 10.1177/1362361320985658. PubMed DOI

THAYER JF, LANE RD. A model of neurovisceral integration in emotion regulation and dysregulation. J Affect Disord. 2000;61:201–216. doi: 10.1016/S0165-0327(00)00338-4. PubMed DOI

TOMOVA A, HUSAROVA V, LAKATOSOVA S, BAKOS J, VLKOVA B, BABINSKA K, OSTATNIKOVA D. Gastrointestinal microbiota in children with autism in Slovakia. Physiol Behav. 2015;138:179–187. doi: 10.1016/j.physbeh.2014.10.033. PubMed DOI

TOMOVA A, SOLTYS K, REPISKA G, PALKOVA L, FILCIKOVA D, MINARIK G, TURNA J, PROCHOTSKA K, BABINSKA K, OSTATNIKOVA D. Specificity of gut microbiota in children with autism spectrum disorder in Slovakia and its correlation with astrocytes activity marker and specific behavioural patterns. Physiol Behav. 2020:214. doi: 10.1016/j.physbeh.2019.112745. PubMed DOI

TONHAJZEROVA I, FARSKY I, MESTANIK M, VISNOVCOVA Z, MESTANIKOVA A, HRTANEK I, ONDREJKA I. Symbolic dynamics of heart rate variability - A promising tool to investigate cardiac sympathovagal control in attention deficit/hyperactivity disorder (ADHD)? Can J Physiol Pharmacol. 2016;94:579–587. doi: 10.1139/cjpp-2015-0375. PubMed DOI

TONHAJZEROVA I, ONDREJKA I, JAVORKA K, TURIANIKOVA Z, FARSKY I, JAVORKA M. Cardiac autonomic regulation is impaired in girls with major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:613–618. doi: 10.1016/j.pnpbp.2010.02.023. PubMed DOI

VISNOVCOVA Z, MESTANIK M, JAVORKA M, MOKRA D, GALA M, JURKO A, CALKOVSKA A, TONHAJZEROVA I. Complexity and time asymmetry of heart rate variability are altered in acute mental stress. Physiol Meas. 2014;35:1319–1334. doi: 10.1088/0967-3334/35/7/1319. PubMed DOI

VOSS BA, SCHULZ S, SCHROEDER R, BAUMERT M, CAMINAL P. Methods derived from nonlinear dynamics for analysing heart rate variability. Philos Trans R Soc A Math Phys Eng Sci. 2009;367:277–296. doi: 10.1098/rsta.2008.0232. PubMed DOI

WALLENSTEN J, ÅSBERG M, NYGREN Å, SZULKIN R, WALLÉN H, MOBARREZ F, NAGER A. Possible biomarkers of chronic stress induced exhaustion - A longitudinal study. PLoS One. 2016;11:e0153924. doi: 10.1371/journal.pone.0153924. PubMed DOI PMC

XU N, LI X, ZHONG Y. Inflammatory cytokines: Potential biomarkers of immunologic dysfunction in autism spectrum disorders. Mediators Inflamm. 2015;2015:531518. doi: 10.1155/2015/531518. PubMed DOI PMC

YOSHIMOTO T, EGUCHI K, SAKURAI H, ODMICHI Y, HASHIMOTO T, ODMICHI M, MORIMOTO A, YAMAGUCHI Y, USHIDA T, IWASE S, SUGENOYA J, KUMAZAWA T. Frequency components of systolic blood pressure variability reflect vasomotor and cardiac sympathetic functions in conscious rats. J Physiol Sci. 2011;61:373–383. doi: 10.1007/s12576-011-0158-7. PubMed DOI PMC

Effect of Selected Music Soundtracks on Cardiac Vagal Control and Complexity Assessed by Heart Rate Variability

Electromagnetic fields - do they pose a cardiovascular risk?