Yonsei Med J.  2015 Sep;56(5):1365-1371. 10.3349/ymj.2015.56.5.1365.

Changes of Heart Rate Variability during Methylphenidate Treatment in Attention-Deficit Hyperactivity Disorder Children: A 12-Week Prospective Study

Affiliations
  • 1Department of Psychiatry, Korea University, College of Medicine, Seoul, Korea. npboard@korea.ac.kr

Abstract

PURPOSE
The aim of this study was to clarify the relationship between the autonomic nervous system and attention deficit hyperactivity disorder (ADHD) rating scales and to evaluate the usefulness of heart rate variability (HRV) as a psychophysiological biomarker for ADHD.
MATERIALS AND METHODS
Subjects were recruited from outpatients in the Department of Child and Adolescent Psychiatry at the Korea University Medical Center from August 2007 to December 2010. Subjects received methylphenidate. Time- and frequency-domain analyses of HRV, the Korean ADHD rating scale (K-ARS), and computerized ADHD diagnostic system were evaluated before treatment. After a 12-week period of medication administration, we repeated the HRV measurements and K-ARS rating.
RESULTS
Eighty-six subjects were initially enrolled and 37 participants completed the 12-week treatment and HRV measurements subsequent to the treatment. Significant correlations were found between the K-ARS inattention score and some HRV parameters. All of the HRV parameters, except the standard deviations of the normal-to-normal interval, very low frequency, and low frequency to high frequency, showed a significant positive correlation between baseline and endpoint measures in completers. High frequency (HF) and the square root of the mean squared differences of successive normal-to-normal intervals (RMSSD), which are related to parasympathetic vagal tone, showed significant decreases from baseline to endpoint.
CONCLUSION
The HRV test was shown to be reproducible. The decrease in HF and RMSSD suggests that parasympathetic dominance in ADHD can be altered by methylphenidate treatment. It also shows the possibility that HRV parameters can be used as psychophysiological markers in the treatment of ADHD.

Keyword

Attention deficit hyperactivity disorder; heart rate variability; methylphenidate; autonomic nervous system

MeSH Terms

Adolescent
Attention/drug effects/*physiology
Attention Deficit Disorder with Hyperactivity/diagnosis/*drug therapy
Autonomic Nervous System/physiopathology
Biomarkers
Central Nervous System Stimulants/pharmacology/*therapeutic use
Child
Female
Heart Rate/*drug effects/physiology
Humans
Male
Methylphenidate/pharmacology/*therapeutic use
Prospective Studies
Republic of Korea
Treatment Outcome
Biomarkers
Central Nervous System Stimulants
Methylphenidate

Reference

1. Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA. The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry. 2007; 164:942–948.
Article
2. Costello EJ, Mustillo S, Erkanli A, Keeler G, Angold A. Prevalence and development of psychiatric disorders in childhood and adolescence. Arch Gen Psychiatry. 2003; 60:837–844.
Article
3. Gaillard AW. Comparing the concepts of mental load and stress. Ergonomics. 1993; 36:991–1005.
4. Mulder G. The concept and measurement of mental effort. In : Hockey RJ, Gaillard AWK, Coles MGH, editors. Energetics and human information processing. 1986. p. 175–198.
5. Fairclough SH, Houston K. A metabolic measure of mental effort. Biol Psychol. 2004; 66:177–190.
Article
6. Kline KP, Ginsburg GP, Johnston JR. T-wave amplitude: relationships to phasic RSA and heart period changes. Int J Psychophysiol. 1998; 29:291–301.
Article
7. Gaultney JF, Kipp K, Weinstein J, McNeill J. Inhibition and Mental Effort in Attention Deficit Hyperactivity Disorder. J Dev Phys Disabil. 1999; 11:105–114.
8. Jennings JR, van der Molen MW, Pelham W, Debski KB, Hoza B. Inhibition in boys with attention deficit hyperactivity disorder as indexed by heart rate change. Dev Psychol. 1997; 33:308–318.
Article
9. Kristal-Boneh E, Raifel M, Froom P, Ribak J. Heart rate variability in health and disease. Scand J Work Environ Health. 1995; 21:85–95.
10. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Eur Heart J. 1996; 17:354–381.
11. Hjortskov N, Rissén D, Blangsted AK, Fallentin N, Lundberg U, Søgaard K. The effect of mental stress on heart rate variability and blood pressure during computer work. Eur J Appl Physiol. 2004; 92:84–89.
12. Buchhorn R, Conzelmann A, Willaschek C, Störk D, Taurines R, Renner TJ. Heart rate variability and methylphenidate in children with ADHD. Atten Defic Hyperact Disord. 2012; 4:85–91.
13. Negrao BL, Bipath P, van der Westhuizen D, Viljoen M. Autonomic correlates at rest and during evoked attention in children with attention-deficit/hyperactivity disorder and effects of methylphenidate. Neuropsychobiology. 2011; 63:82–91.
Article
14. Wilens TE. Mechanism of action of agents used in attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2006; 67:Suppl 8. 32–38.
15. Berridge CW, Devilbiss DM, Andrzejewski ME, Arnsten AF, Kelley AE, Schmeichel B, et al. Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function. Biol Psychiatry. 2006; 60:1111–1120.
Article
16. Swanson CJ, Perry KW, Koch-Krueger S, Katner J, Svensson KA, Bymaster FP. Effect of the attention deficit/hyperactivity disorder drug atomoxetine on extracellular concentrations of norepinephrine and dopamine in several brain regions of the rat. Neuropharmacology. 2006; 50:755–760.
Article
17. Awudu GA, Besag FM. Cardiovascular effects of methylphenidate, amphetamines and atomoxetine in the treatment of attention-deficit hyperactivity disorder: an update. Drug Saf. 2014; 37:661–676.
Article
18. Shibao C, Raj SR, Gamboa A, Diedrich A, Choi L, Black BK, et al. Norepinephrine transporter blockade with atomoxetine induces hypertension in patients with impaired autonomic function. Hypertension. 2007; 50:47–53.
19. Connor D. Once a day Concerta methylphenidate was equivalent to 3 times daily methylphenidate in children with ADHD. Evid Based Ment Health. 2002; 5:20.
Article
20. Coghill D, Banaschewski T, Zuddas A, Pelaz A, Gagliano A, Doepfner M. Long-acting methylphenidate formulations in the treatment of attention-deficit/hyperactivity disorder: a systematic review of head-to-head studies. BMC Psychiatry. 2013; 13:237.
Article
21. DuPaul GJ, Power TJ, Anastopoulos AD, Reid R. ADHD Rating Scale-IV: Checklists, Norms, and Clinical Interpretation. New York: Guilford Press;1998.
22. So YK, Noh JS, Kim YS, Ko SG, Koh YJ. The reliability and validity of Korean parent and teacher ADHD Rating Scale. J Korean Neuropsychiatr Assoc. 2002; 41:283–289.
23. DuPaul GJ. Parent and Teacher Ratings of Adhd Symptoms: Psychometric Properties in a Community-Based Sample. J Clin Child Psychol. 1991; 20:245–253.
24. Shin MS, Cho S, Chun SY, Hong KE. A study of the development and standardization of ADHD diagnostic system. J Child Adolesc Psychiatry. 2000; 11:91–99.
25. Malliani A, Lombardi F, Pagani M. Power spectrum analysis of heart rate variability: a tool to explore neural regulatory mechanisms. Br Heart J. 1994; 71:1–2.
26. Sandercock G. Normative values, reliability and sample size estimates in heart rate variability. Clin Sci (Lond). 2007; 113:129–130.
Article
27. Thayer JF, Yamamoto SS, Brosschot JF. The relationship of autonomic imbalance, heart rate variability and cardiovascular disease risk factors. Int J Cardiol. 2010; 141:122–131.
Article
28. Berntson GG, Lozano DL, Chen YJ. Filter properties of root mean square successive difference (RMSSD) for heart rate. Psychophysiology. 2005; 42:246–252.
Article
29. Timimi S, Taylor E. ADHD is best understood as a cultural construct. Br J Psychiatry. 2004; 184:8–9.
Article
30. Tonhajzerova I, Ondrejka I, Adamik P, Hruby R, Javorka M, Trunkvalterova Z, et al. Changes in the cardiac autonomic regulation in children with attention deficit hyperactivity disorder (ADHD). Indian J Med Res. 2009; 130:44–50.
31. Yeragani VK. Heart rate and blood pressure variability: implications for psychiatric research. Neuropsychobiology. 1995; 32:182–191.
Article
32. Thayer JF, Lane RD. The role of vagal function in the risk for cardiovascular disease and mortality. Biol Psychol. 2007; 74:224–242.
Article
33. Börger N, van der Meere J. Motor control and state regulation in children with ADHD: a cardiac response study. Biol Psychol. 2000; 51:247–267.
Article
34. Porges SW. Orienting in a defensive world: mammalian modifications of our evolutionary heritage. A Polyvagal Theory. Psychophysiology. 1995; 32:301–318.
Article
35. Porges SW, Doussard-Roosevelt JA, Stifter CA, McClenny BD, Riniolo TC. Sleep state and vagal regulation of heart period patterns in the human newborn: an extension of the polyvagal theory. Psychophysiology. 1999; 36:14–21.
Article
36. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart rate variability: standards of measurement, physiological interpretation and clinical use. Circulation. 1996; 93:1043–1065.
37. Pyetan E, Akselrod S. Do the high-frequency indexes of HRV provide a faithful assessment of cardiac vagal tone? A critical theoretical evaluation. IEEE Trans Biomed Eng. 2003; 50:777–783.
Article
38. DeGiorgio CM, Miller P, Meymandi S, Chin A, Epps J, Gordon S, et al. RMSSD, a measure of vagus-mediated heart rate variability, is associated with risk factors for SUDEP: the SUDEP-7 Inventory. Epilepsy Behav. 2010; 19:78–81.
Article
39. Beauchaine T. Vagal tone, development, and Gray's motivational theory: toward an integrated model of autonomic nervous system functioning in psychopathology. Dev Psychopathol. 2001; 13:183–214.
Article
40. Bange F, Le Heuzey MF, Acquaviva E, Delorme R, Mouren MC. [Cardiovascular risks and management during Attention Deficit Hyperactivity Disorder treatment with methylphenidate]. Arch Pediatr. 2014; 21:108–112.
Full Text Links
  • YMJ
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr