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Brief Report: Can a Composite Heart Rate Variability Biomarker Shed New Insights About Autism Spectrum Disorder in School-Aged Children?

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Abstract

Several studies show altered heart rate variability (HRV) in autism spectrum disorder (ASD), but findings are neither universal nor specific to ASD. We apply a set of linear and nonlinear HRV measures—including phase rectified signal averaging—to segments of resting ECG data collected from school-age children with ASD, age-matched typically developing controls, and children with other psychiatric conditions characterized by altered HRV (conduct disorder, depression). We use machine learning to identify time, frequency, and geometric signal-analytical domains that are specific to ASD (receiver operating curve area = 0.89). This is the first study to differentiate children with ASD from other disorders characterized by altered HRV. Despite a small cohort and lack of external validation, results warrant larger prospective studies.

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References

  • Achenbach, T. M. (1991). Manual for the child behavior checklist/4-18 and 1991 profile. Burlington, VT: University of Vermont, Department of Psychiatry.

    Google Scholar 

  • American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: American Psychiatric Association.

    Google Scholar 

  • Bal, E., Harden, E., Lamb, D., Van Hecke, A. V., Denver, J. W., & Porges, S. W. (2010). Emotion recognition in children with autism spectrum disorders: Relations to eye gaze and autonomic state. Journal of Autism and Developmental Disorders, 40, 358–370. https://doi.org/10.1007/s10803-009-0884-3.

    Article  PubMed  Google Scholar 

  • Bauer, A., Kantelhardt, J. W., Barthel, P., Schneider, R., Mäkikallio, T., Ulm, K., et al. (2006a). Deceleration capacity of heart rate as a predictor of mortality after myocardial infarction: Cohort study. Lancet, 367, 1674–1681. https://doi.org/10.1016/S0140-6736(06)68735-7.

    Article  PubMed  Google Scholar 

  • Bauer, A., Kantelhardt, J. W., Bunde, A., Barthel, P., Schneider, R., Malik, M., et al. (2006b). Phase-rectified signal averaging detects quasi-periodicities in non-stationary data. Physica A: Statistical Mechanics and its Applications, 364, 423–434. https://doi.org/10.1016/j.physa.2005.08.080.

    Article  Google Scholar 

  • Beauchaine, T. (2001). Vagal tone, development, and Gray’s motivational theory: Toward an integrated model of autonomic nervous system functioning in psychopathology. Development and Psychopathology, 13, 183–214. https://doi.org/10.1017/S0954579401002012.

    Article  PubMed  Google Scholar 

  • Beauchaine, T. P. (2012). Physiological markers of emotion and behavior dysregulation in externalizing psychopathology. Monographs of the Society for Research in Child Development, 77, 79–86. https://doi.org/10.1111/j.1540-5834.2011.00665.x.

    Article  PubMed  PubMed Central  Google Scholar 

  • Beauchaine, T. P. (2015). Respiratory sinus arrhythmia: A transdiagnostic biomarker of emotion dysregulation and psychopathology. Current Opinion in Psychology, 3, 43–47. https://doi.org/10.1016/j.copsyc.2015.01.017.

    Article  PubMed  PubMed Central  Google Scholar 

  • Beauchaine, T. P., & Thayer, J. F. (2015). Heart rate variability as a transdiagnostic biomarker of psychopathology. International Journal of Psychophysiology, 98, 338–350. https://doi.org/10.1016/j.ijpsycho.2015.08.004.

    Article  PubMed  Google Scholar 

  • Benevides, T. W., & Lane, S. J. (2015). A review of cardiac autonomic measures: Considerations for examination of physiological response in children with autism spectrum disorder. Journal of Autism and Developmental Disorders, 45, 560–575.

    Article  PubMed  Google Scholar 

  • Berry, D., Palmer, A., Distefano, R., & Masten, A. (2019). Autonomic complexity and emotion (dys-)regulation in early childhood across high- and low-risk contexts. Development and Psychopathology, 31, 1173–1190. https://doi.org/10.1017/S0954579419000683.

    Article  PubMed  PubMed Central  Google Scholar 

  • Billeci, L., Tonacci, A., Narzisi, A., Manigrasso, Z., Varanini, M., Fulceri, F., et al. (2018). Heart rate variability during a joint attention task in toddlers with autism spectrum disorders. Frontiers in Physiology, 9, 467. https://doi.org/10.3389/fphys.2018.00467.

    Article  PubMed  PubMed Central  Google Scholar 

  • Bravi, A., Longtin, A., & Seely, A. J. (2011). Review and classification of variability analysis techniques with clinical applications. Biomedical Engineering Online. https://doi.org/10.1186/1475-925X-10-90.

    Article  PubMed  PubMed Central  Google Scholar 

  • Buitinck, L., Louppe, G., Blondel, M., Pedregosa, F., Mueller, A., Grisel, O., & Varoquaux, G. (2013). API design for machine learning software: Experiences from the scikit-learn project. arXiv:1309.0238 [cs.LG]

  • Bujnakova, I., Ondrejka, I., Mestanik, M., Visnovcova, Z., Mestanikova, A., Hrtanek, I., et al. (2016). Autism spectrum disorder is associated with autonomic underarousal. Physiological Research, 65, S673–S682.

    Article  PubMed  Google Scholar 

  • Chen, Tianqi, and Carlos Guestrin. (2016). XGBoost: A scalable tree boosting system. In Proceedings of the 22nd ACM SIGKDD International Conference on Knowledge Discovery and Data Mining, (pp. 785–794). ACM.

  • Crowell, S. E., Beauchaine, T. P., McCauley, E., Smith, C., Stevens, A. L., & Sylvers, P. (2005). Psychological, autonomic, and serotonergic correlates of parasuicidal behavior in adolescent girls. Development and Psychopathology, 17, 1105–1127. https://doi.org/10.1037/0022-006X.73.3.371.

    Article  PubMed  Google Scholar 

  • Daluwatte, C., Miles, J. H., Christ, S. E., Beversdorf, D. Q., Takahashi, T. N., & Yao, G. (2012). Atypical pupillary light reflex and heart rate variability in children with autism spectrum disorder. Journal of Autism and Developmental Disorders, 43, 1910–1925. https://doi.org/10.1007/s10803-012-1741-3.

    Article  Google Scholar 

  • Doussard-Roosevelt, J. A., Porges, S. W., Scanlon, J. W., Alemi, B., & Scanlon, K. B. (1997). Vagal regulation of heart rate in the prediction of developmental outcome for very low birth weight preterm infants. Child Development, 68, 173–186.

    Article  PubMed  Google Scholar 

  • Durosier, L. D., Herry, C. L., Cortes, M., Cao, M., Burns, P., Desrocher, A., et al. (2015). Does heart rate variability reflect the systemic inflammatory response in a fetal sheep model of lipopolysaccharide-induced sepsis? Physiological Measurement, 36, 2089–2102.

    Article  PubMed  PubMed Central  Google Scholar 

  • Fabes, R. A., Eisenberg, N., & Eisenbud, L. (1993). Behavioral and physiological correlates of children's reactions to others in distress. Developmental Psychology, 29, 655–663.

    Article  Google Scholar 

  • Frasch, M. G., Herry, C. L., Niu, Y., & Giussani, D. A. (2017). First evidence of intrinsic fetal heart rate variability affected by chronic fetal hypoxia. Reproductive Sciences, 24, 198A.

    Google Scholar 

  • Frasch, M. G., Lobmaier, S. M., Stampalija, T., Desplats, P., Pallarés, M. E., Pastor, V., et al. (2018). Non-invasive biomarkers of fetal brain development reflecting prenatal stress: An integrative multi-scale multi-species perspective on data collection and analysis. Neuroscience and Biobehavioral Reviews. https://doi.org/10.1016/j.neubiorev.2018.05.026.

    Article  PubMed  Google Scholar 

  • Frasch, M. G., Müller, T., Weiss, C., Schwab, K., Schubert, H., & Schwab, M. (2009). Heart rate variability analysis allows early asphyxia detection in ovine fetus. Reproductive Sciences, 16, 509–517. https://doi.org/10.1177/1933719108327597.

    Article  PubMed  Google Scholar 

  • Frasch, M. G., Xu, Y., Stampalija, T., Durosier, L. D., Herry, C., Wang, X., et al. (2014). Correlating multidimensional fetal heart rate variability analysis with acid-base balance at birth. Physiological Measurement, 35, L1–L12.

    Article  PubMed  Google Scholar 

  • Friedman, J. H. (2001). Greedy function approximation: A gradient boosting machine. Annals of Statistics, 29(5), 1189–1232.

    Article  Google Scholar 

  • Gadow, K. D., & Sprafkin, J. (1997). Childhood Symptom Inventory 4 norms manual. Stony Brook, NY: Checkmate Plus.

    Google Scholar 

  • Gresham, F., & Elliott, S. (2008). Social skills improvements system. Minneapolis, MN: Pearson.

    Google Scholar 

  • Guy, L., Souders, M., Bradstreet, L., Delussey, C., & Herrington, J. D. (2014). Brief report: Emotion regulation and respiratory sinus arrhythmia in autism spectrum disorder. Journal of Autism and Developmental Disorders, 44, 2614–2620. https://doi.org/10.1007/s10803-014-2124-8.

    Article  PubMed  Google Scholar 

  • Hastings, P. D., Nuselovici, J. N., Utendale, W. T., Coutya, J., McShane, K. E., & Sullivan, C. (2008). Applying the polyvagal theory to children’s emotion regulation: Social context, socialization, and adjustment. Biological Psychology, 79, 299–306.

    Article  PubMed  Google Scholar 

  • Heilman, K. J., Bal, E., Bazhenova, O. V., & Porges, S. W. (2007). Respiratory sinus arrhythmia and tympanic membrane compliance predict spontaneous eye gaze behaviors in young children: A pilot study. Developmental Psychobiology, 49, 531–542. https://doi.org/10.1002/dev.20237.

    Article  PubMed  Google Scholar 

  • Herry, C. L., Burns, P., Desrochers, A., Fecteau, G., Durosier, L. D., Cao, M., et al. (2019). Vagal contributions to fetal heart rate variability: An omics approach. Physiological Measurement. https://doi.org/10.1088/1361-6579/ab21ae.

    Article  PubMed  Google Scholar 

  • Herry, C. L., Cortes, M., Wu, H. T., Durosier, L. D., Cao, M., Burns, P., et al. (2016). Temporal patterns in sheep fetal heart rate variability correlate to systemic cytokine inflammatory response: A methodological exploration of monitoring potential using complex signals bioinformatics. PLoS ONE, 11, e0153515. https://doi.org/10.1371/journal.pone.0153515.

    Article  PubMed  PubMed Central  Google Scholar 

  • Koenig, J., Kemp, A. H., Beauchaine, T. P., Thayer, J. F., & Kaess, M. (2016). Depression and resting state heart rate variability in children and adolescents—A systematic review and meta-analysis. Clinical Psychology Review, 46, 136–150.

    Article  PubMed  Google Scholar 

  • Lainhart, J. E., Bigler, E. D., Bocian, M., Coon, H., Dinh, E., Dawson, G., et al. (2006). Head circumference and height in autism: A study by the collaborative program of excellence in autism. American Journal of Medical Genetics Part A, 140A, 2257–2274.

    Article  Google Scholar 

  • Levine, T. P., Sheinkopf, S. J., Pescosolido, M., Rodino, A., Elia, G., & Lester, B. (2012). Physiologic arousal to social stress in children with autism spectrum disorders: A pilot study. Research in Autism Spectrum Disorders, 6, 177–183.

    Article  PubMed  PubMed Central  Google Scholar 

  • Li, D., Karnath, H. O., & Xu, X. (2017). Candidate biomarkers in children with autism spectrum disorder: A review of MRI studies. Neuroscience Bulletin, 33, 219–237.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lobmaier, S. M., Muller, A., Zelgert, C., Shen, C., Su, P. C., Schmidt, G., et al. (2019). Fetal heart rate variability responsiveness to maternal stress, non-invasively detected from maternal transabdominal ECG. Archives of Gynecology and Obstetrics. https://doi.org/10.1007/s00404-019-05390-8.

    Article  PubMed  Google Scholar 

  • Lord, C., Rutter, M., DiLavore, P. C., & Risi, S. (2003). Autism diagnostic observation schedule manual. Los Angeles: Western Psychological Services.

    Google Scholar 

  • Lord, C., Rutter, M., & Le Couteur, A. (1994). Autism diagnostic interview-revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. Journal of Autism and Developmental Disorders, 24, 659–685. https://doi.org/10.1007/BF02172145.

    Article  PubMed  Google Scholar 

  • Ming, X., Julu, P. O. O., Brimacombe, M., Connor, S., & Daniels, M. L. (2005). Reduced cardiac parasympathetic activity in children with autism. Brain and Development, 27, 509–516. https://doi.org/10.1016/j.braindev.2005.01.003.

    Article  PubMed  Google Scholar 

  • Neuhaus, E., Bernier, R., & Beauchaine, T. P. (2014). Brief report: Social skills, internalizing and externalizing symptoms, and respiratory sinus arrhythmia in autism. Journal of Autism and Developmental Disorders, 44, 730–737. https://doi.org/10.1007/s10803-013-1923-7.

    Article  PubMed  Google Scholar 

  • Neuhaus, E., Bernier, R. A., & Beauchaine, T. P. (2015). Electrodermal Response to Reward and Non-Reward Among Children With Autism. Autism Research, 8 (4), 357–370.

    Article  PubMed  Google Scholar 

  • Patriquin, M. A., Hartwig, E. M., Friedman, B. H., Porges, S. W., & Scarpa, A. (2019). Autonomic response in autism spectrum disorder: Relationship to social and cognitive functioning. Biological Psychology, 145, 185–197.

    Article  PubMed  Google Scholar 

  • Patriquin, M. A., Lorenzi, J., Scarpa, A., & Bell, M. A. (2014). Developmental trajectories of respiratory sinus arrhythmia: Associations with social responsiveness. Developmental Psychobiology, 56, 317–326. https://doi.org/10.1002/dev.21100.

    Article  PubMed  Google Scholar 

  • Peltola, M. A. (2012). Role of editing of R-R intervals in the analysis of heart rate variability. Frontiers in Physiology, 23, 148. https://doi.org/10.3389/fphys.2012.00148.

    Article  Google Scholar 

  • Porges, S. W. (2003). The Polyvagal theory: Phylogenetic contributions to social behavior. Physiology and Behavior, 79, 503–513.

    Article  PubMed  Google Scholar 

  • Porges, S. W. (2007). The polyvagal perspective. Biological Psychology, 74, 116–143.

    Article  PubMed  Google Scholar 

  • Rutter, M., Bailey, A., & Lord, C. (2003). Social Communication Questionnaire (SCQ) Manual. Los Angeles: Western Psychological Services.

    Google Scholar 

  • Sassi, R., Cerutti, S., Lombardi, F., Malik, M., Huikuri, H. V., Peng, C.-K., et al. (2015). Advances in heart rate variability signal analysis: Joint position statement by the e-Cardiology ESC Working Group and the European Heart Rhythm Association co-endorsed by the Asia Pacific Heart Rhythm Society. Europace, 17, 1341–1353. https://doi.org/10.1093/europace/euv015.

    Article  PubMed  Google Scholar 

  • Shader, T. M., Gatzke-Kopp, L. M., Crowell, S. E., Reid, M. J., Thayer, J. F., Vasey, M. W., et al. (2018). Quantifying respiratory sinus arrhythmia: Effects of misspecifying breathing frequencies across development. Development and Psychopathology, 30, 351–366. https://doi.org/10.1017/S0954579417000669.

    Article  PubMed  Google Scholar 

  • Shaffer, F., & Ginsberg, J. P. (2017). An overview of heart rate variability metrics and norms. Frontiers in Public Health, 5, 258. https://doi.org/10.3389/fpubh.2017.00258.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sheinkopf, S. J., Levine, T. P., McCormick, C. E. B., Puggioni, G., Conradt, E., Lagasse, L. L., et al. (2019). Developmental trajectories of autonomic functioning in autism from birth to early childhood. Biological Psychology, 142, 13–18.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sheinkopf, S. J., Neal-Beevers, A. R., Levine, T. P., Miller-Loncar, C., & Lester, B. (2013). Parasympathetic response profiles related to social functioning in young children with autistic disorder. Autism Research and Treatment, 2013, 868396. https://doi.org/10.1155/2013/868396.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sparrow, S. S., Cicchetti, D., & Balla, D. A. (2005). Vineland Adaptive Behavior Scales (2nd ed.). Circle Pines, MN: American Guidance Service.

    Google Scholar 

  • Sprafkin, J., Gadow, K. D., Salisbury, H., Schneider, J., & Loney, J. (2002). Further evidence of reliability and validity of the Child Symptom Inventory-4: Parent Checklist in clinically referred boys. Journal of Clinical Child and Adolescent Psychology, 31, 513–524.

    Article  PubMed  Google Scholar 

  • Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. (1996). Heart rate variability: Standards of measurement, physiological interpretation, and clinical use. Circulation, 93, 1043–1065.

    Article  Google Scholar 

  • Taylor, Z. E., Eisenberg, N., & Spinrad, T. L. (2015). Respiratory sinus arrhythmia, effortful control, and parenting as predictors of children’s sympathy across early childhood. Developmental Psychology, 51, 17–25.

    Article  PubMed  Google Scholar 

  • Thapa, R., Alvares, G. A., Zaidi, T. A., Thomas, E. E., Hickie, I. B., Park, S. H., et al. (2019). Reduced heart rate variability in adults with autism spectrum disorder. Autism Research, 12, 922–930. https://doi.org/10.1002/aur.2104.

    Article  PubMed  Google Scholar 

  • Thayer, J. F., & Lane, R. D. (2000). A model of neurovisceral integration in emotion regulation and dysregulation. Journal of Affective Disorders, 61, 201–216.

    Article  PubMed  Google Scholar 

  • Vaughan Van Hecke, A., Lebow, J., Bal, E., Lamb, D., Harden, E., Kramer, A., et al. (2009). Electroencephalogram and heart rate regulation to familiar and unfamiliar people in children with autism spectrum disorders. Child Development, 80, 1118–1133. https://doi.org/10.1111/j.1467-8624.2009.01320.x.

    Article  PubMed  Google Scholar 

  • Walsh, P., Elsabbagh, M., Bolton, P., & Singh, I. (2011). In search of biomarkers for autism: Scientific, social and ethical challenges. Nature Reviews Neuroscience, 12, 603–612.

    Article  PubMed  Google Scholar 

  • Watson, L. R., Roberts, J. E., Baranek, G. T., Mandulak, K. C., & Dalton, J. C. (2012). Behavioral and physiological responses to child-directed speech of children with autism spectrum disorders or typical development. Journal of Autism and Developmental Disorders, 42, 1616–1629.

    Article  PubMed  PubMed Central  Google Scholar 

  • Xiao, M., Yan, H., Song, J., Yang, Y., & Yang, X. (2013). Sleep stages classification based on heart rate variability and random forest. Biomedical Signal Processing and Control, 8(6), 624–633.

    Article  Google Scholar 

  • Zwaigenbaum, L., & Penner, M. (2018). Autism spectrum disorder: Advances in diagnosis and evaluation. BMJ, 361, k1674. https://doi.org/10.1136/bmj.k1674.

    Article  PubMed  Google Scholar 

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Acknowledgments

Supported in part by CIHR and FRQS (MGF) and Sloan (HTW). Some data analyzed in the current study were presented previously (e.g., Neuhaus et al. 2014) as described in the text.

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MGF and HTW Study conceptualization; Data processing/analysis; Manuscript draft, revision, and final approval. CS and AM Data processing/analysis; Manuscript revision and final approval. EN Study conceptualization; Data collection; Data processing/analysis; Manuscript draft, revision, and final approval. RAB Study conceptualization; Manuscript revision and final approval. DK Data processing; Data processing/analysis; Manuscript revision and final approval. TPB Study conceptualization; Data processing/analysis; Manuscript revision and final approval.

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Correspondence to Emily Neuhaus.

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Frasch, M.G., Shen, C., Wu, HT. et al. Brief Report: Can a Composite Heart Rate Variability Biomarker Shed New Insights About Autism Spectrum Disorder in School-Aged Children?. J Autism Dev Disord 51, 346–356 (2021). https://doi.org/10.1007/s10803-020-04467-7

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