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

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          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.

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          Orienting in a defensive world: mammalian modifications of our evolutionary heritage. A Polyvagal Theory.

          STEPHEN PORGES (1995)
          The vagus, the 10th cranial nerve, contains pathways that contribute to the regulation of the internal viscera, including the heart. Vagal efferent fibers do not originate in a common brainstem structure. The Polyvagal Theory is introduced to explain the different functions of the two primary medullary source nuclei of the vagus: the nucleus ambiguus (NA) and the dorsal motor nucleus (DMNX). Although vagal pathways from both nuclei terminate on the sinoatrial node, it is argued that the fibers originating in NA are uniquely responsible for respiratory sinus arrhythmia (RSA). Divergent shifts in RSA and heart rate are explained by independent actions of DMNX and NA. The theory emphasizes a phylogenetic perspective and speculates that mammalian, but not reptilian, brainstem organization is characterized by a ventral vagal complex (including NA) related to processes associated with attention, motion, emotion, and communication. Various clinical disorders, such as sudden infant death syndrome and asthma, may be related to the competition between DMNX and NA.
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            The effect of mental stress on heart rate variability and blood pressure during computer work.

            Nis Hjortskov, Karen Søgaard, Anne K. Blangsted … (2004)
            The aim was to evaluate the cardiovascular and subjective stress response to a combined physical and mental workload, and the effect of rest. Twelve females who had no prior experience of laboratory experiments participated in the study. Computer-work-related mental stressors were either added to or removed from a standardized computer work session in the laboratory. Beat-to-beat blood pressure and electrocardiogram (ECG) were recorded continuously during the experiment. The participants reported subjective experiences of stress in six categories using an 11-point scale before and at the end of the work. Heart rate variability (HRV) variables were calculated from the ECG recordings, and a reduction in the high-frequency component of HRV and an increase in the low- to high-frequency ratio were observed in the stress situation compared to the control session. No changes were seen in the low-frequency component of HRV. The stressors induced an increase in blood pressure compared to baseline that persisted, and for the diastolic pressure it even increased in the subsequent control session. No differences were observed for subjective experience of stress with the exception of a time trend in the exhaustion scale, i.e. a progression in reported exhaustion with time. The results-and the dissociation between HRV and blood pressure variables-indicate that HRV is a more sensitive and selective measure of mental stress. It could be speculated that heart rate-derived variables reflect a central pathway in cardiovascular control mechanisms ("central command"), while the blood pressure response is more influenced by local conditions in the working muscles that partly mask the effect of changes in mental workloads. In the rest period after each work session, HRV and blood pressure variables were partly normalized as expected. However, an 8-min period of rest was insufficient to restore blood pressure to resting values.
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              Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function.

              David Devilbiss, Craig Berridge, David Kelley … (2006)
              Low doses of psychostimulants, such as methylphenidate (MPH), are widely used in the treatment of attention-deficit/hyperactivity disorder (ADHD). Surprisingly little is known about the neural mechanisms that underlie the behavioral/cognitive actions of these drugs. The prefrontal cortex (PFC) is implicated in ADHD. Moreover, dopamine (DA) and norepinephrine (NE) are important modulators of PFC-dependent cognition. To date, the actions of low-dose psychostimulants on PFC DA and NE neurotransmission are unknown. In vivo microdialysis was used to compare the effects of low-dose MPH on NE and DA efflux within the PFC and select subcortical fields in male rats. Doses used (oral, 2.0 mg/kg; intraperitoneal, .25-1.0 mg/kg) were first determined to produce clinically relevant plasma concentrations and to facilitate both PFC-dependent attention and working memory. At low doses that improve PFC-dependent cognitive function and that are devoid of locomotor-activating effects, MPH substantially increases NE and DA efflux within the PFC. In contrast, outside the PFC these doses of MPH have minimal impact on NE and DA efflux. The current observations suggest that the therapeutic actions of low-dose psychostimulants involve the preferential activation of catecholamine neurotransmission within the PFC.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Yonsei Med J
                Journal ID (iso-abbrev): Yonsei Med. J
                Journal ID (publisher-id): YMJ
                Title: Yonsei Medical Journal
                Publisher: Yonsei University College of Medicine
                ISSN (Print): 0513-5796
                ISSN (Electronic): 1976-2437
                Publication date (Print): 01 September 2015
                Publication date (Electronic): 29 July 2015
                Volume: 56
                Issue: 5
                Pages: 1365-1371
                Affiliations
                Department of Psychiatry, Korea University, College of Medicine, Seoul, Korea.
                Author notes
                Corresponding author: Dr. Moon-Soo Lee, Department of Psychiatry, Korea University, College of Medicine, Korea University Guro Hospital, 148 Gurodong-ro, Guro-gu, Seoul 152-703, Korea. Tel: 82-2-459-1579, Fax: 82-2-852-1937, npboard@ 123456korea.ac.kr
                Article
                DOI: 10.3349/ymj.2015.56.5.1365
                PMC ID: 4541668
                PubMed ID: 26256981
                SO-VID: 67a1ca7d-e033-45e2-911d-2d281a25621c
                Copyright © © Copyright: Yonsei University College of Medicine 2015
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 23 June 2014
                Date revision received : 08 October 2014
                Date accepted : 05 November 2014
                Funding
                Funded by: Korean Foundation of Neuropsychiatric Research
                Categories
                Subject: Original Article
                Subject: Psychiatry, Psychology

                ScienceOpen disciplines: Medicine
                Keywords: attention deficit hyperactivity disorder,heart rate variability,methylphenidate,autonomic nervous system
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: attention deficit hyperactivity disorder, heart rate variability, methylphenidate, autonomic nervous system

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