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Open access

I. Tonhajzerova, I. Ondrejka, K. Javorka, A. Calkovska and M. Javorka

Cardiac Vagal Control in Depression and Attention Deficit/Hyperactivity Disorder

The importance of the vagus nerve in the two way communication between the brain and the heart has been known for over 100 years. Recently, integrative theories that link central nervous system structures to cardiac vagal regulation, such as the polyvagal theory, have of late emerged. Based on the polyvagal theory, the respiratory sinus arrhythmia (as an index of cardiac vagal control) is considered as a psychophysiological marker of many aspects of behavioural functioning and emotion regulation in both children and adults. Although a lack of sensitive heart rate autonomic control likely reflects impaired cardiac nervous system regulation, the sophisticated brain-heart interactions are incompletely understood. Importantly, cardiac vagal dysregulation is associated with the increased risk of cardiovascular morbidity reflecting various pathophysiological states. Thus, we believe that the identifying of cardiac vagal control changes in mental disorders should represent an initial step towards the understanding of a potential pathomechanisms leading to later cardiac adverse outcomes; especially in children and adolescents.

Open access

Zuzana Visnovcova, A. Calkovska and I. Tonhajzerova


The autonomic nervous system (ANS) is a principal regulatory system for maintaining homeostasis, adaptability and physiological flexibility of the organism at rest as well as in response to stress. In the aspect of autonomic regulatory inputs on the cardiovascular system, recent research is focused on the study of exaggerated/diminished cardiovascular reactivity in response to mental stress as a risk factor for health complications, e.g. hypertension. Thus, the analysis of biological signals reflecting a physiological shift in sympathovagal balance during stress in the manner of vagal withdrawal associated with sympathetic overactivity is important. The heart rate variability, i.e. “beat-to-beat” oscillations of heart rate around its mean value, reflects mainly complex neurocardiac parasympathetic control. The electrodermal activity could represent “antagonistic” sympathetic activity, the so-called “sympathetic arousal” in response to stress. The detailed study of the physiological parameters under various stressful stimuli and in recovery phase using traditional and novel mathematical analyses could reveal discrete alterations in sympathovagal balance. This article summarizes the importance of heart rate variability and electrodermal activity assessment as the potential noninvasive indices indicating autonomic nervous system activity in response to mental stress.

Open access

L. Chladekova, Z. Turianikova, I. Tonhajzerova, A. Calkovska and M. Javorka

Time Irreversibility of Heart Rate Oscillations During Orthostasis

Introduction: Time irreversibility is a characteristic feature of non-equilibrium, complex systems involving cardiovascular control mediated by autonomic nervous system. Its analysis in heart rate variability (HRV) signal represents a new approach to assess cardiovascular regulatory mechanisms. The purpose of this paper was to assess the changes in various time irreversibility indices during the orthostatic test (a balance of autonomic nervous system shifted towards sympathetic predominance). In addition, we tested the behaviour of the selected irreversibility indices in relation to different lengths of analysed data and their mutual dependence.

Methods: We examined the irreversibility of HRV time series obtained from 28 healthy young subjects recorded during 20 minutes in the supine position followed by 15 minutes in the standing position. We used three different time irreversibility indices - Porta's, Guzik's and Costa's indices (P%, G% and A, respectively). The proposed irreversibility indices were derived from data segments containing 300, 600 and 1000 beat-to-beat intervals.

Results: Two of three time irreversibility indices (P% and A) were sensitive to the shift in sympathovagal balance during the orthostatic challenge even when calculated from the shortest data length. Indices were relatively insensitive to data length - there were no significant differences in relation to data length. Despite the difference in algorithms for the calculation of indices P% and A, these are closely mathematically related and do not provide mutually independent information.

Conclusion: We conclude that heart rate irreversibility indices are sensitive to the changes in autonomic tone after the orthostatic challenge even when derived from the 300 interbeat intervals. Porta's index seems to be more sensitive to autonomic nervous balance shift compared to Guzik's index. Costa's index is closely related to P% and do not provide any additional information compared to other indices.

Open access

Mestanlk M., Vlsnovcova Z. and Tonhajzerova I.


The response of autonomic nervous system to mental stress is currently studied as a key role factor in the pathophysiology of stress related diseases. Altered autonomic regulation can result in increased morbidity, potentially affecting (directly or indirectly) any of the organs. Cardiovascular system (CVS) is one of the most sensitive systems to the effect of autonomic outputs. The predictive value of the laboratory stress tests was proved in several studies with CVS pathology. In this study we aimed to assess the autonomic reactivity to different mental stressors (cognitive and emotional) in healthy subjects using electrodermal activity (EDA) as a sensitive psychophysiological marker of sympathetic activity. We found significantly increased EDA in response to all the mental tasks with decrease of the values during recovery periods. However, EDA did not return to the baseline values during recovery periods, potentially indicating the sympathetic arousal during complete stress profile protocol. We suggest EDA presents a well applicable marker of the sympathetic activation, offering a different information about central regulation processes regarding the sympathetic activity compared to cardiac autonomic indices.

Open access

D. Cesneková, I. Ondrejka, M. Oppa, I. Tonhajzerová and G. Nosáľová


Depressive disorder is one of the most common and serious psychiatric diagnosis in paediatric population, often connected with suicidal risk. In recent years, fluoxetine monotherapy is the gold standard in acute phase of depression treatment in children and adolescents, but is not effective enough after an acute phase of treatment. More helpful researches concerning more effective therapeutic strategies of depression in this age are insufficient. The aim of our study is to evaluate the effectiveness and safety of fluoxetine monotherapy in comparison with combined olanzapine/fluoxetine therapy in acute 6-week treatment of depression in adolescence. We found that combined therapeutic strategy, using olanzapine augmentation is predicted to be more useful in the treatment of adolescent depression.

Open access

M. Oppa, I. Ondrejka, D. Cesnekova, I. Tonhajzerova and G. Nosalova


Vortioxetine is a novel antidepressant with two mechanisms of action – direct effect on several serotonin receptors and serotonin reuptake inhibition. Atypical antipsychotics, such as olanzapine, used in the augmentation of antidepressants causes not only a better response to treatment, but also increased number of remissions. The aim of our work was to evaluate the efficacy of vortioxetine monotherapy compared to the combined treatment vortioxetine and olanzapine in adult patients with depression during the acute phase of treatment lasting 6 weeks. Depressive symptomatology was assessed by the MADRS scale, anxiety symptoms were assessed by the HAM-A scale and global clinical impression were evaluated by the CGI-S scale. The number of patients in full-analysis set was 28. The results showed statistically significant improvement in CGI-S for both groups. Patients with vortioxetine monotherapy showed significant improvement in MADRS total score from the third week of treatment (p = 0.009) compared to patients with combined therapy that showed significant improvement since the end of first week of treatment (p = 0.036). Both groups showed significant improvement in HAM-A total score from the second week of treatment. Our results show the possibility of olanzapine in the augmentation strategy in treatment of major depressive disorder in adult patients.

Open access

I Bujnakova, I Ondrejka, M Mestanik, D Fleskova, N Sekaninova, I Farsky and I Tonhajzerova


Background: Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder associated with autonomic nervous system (ANS) abnormalities. Moreover, at least 50% of children with ASD suffer from other comorbid diseases such as anxiety, depression, and attention deficit hyperactivity disorder (ADHD) associated with receiving psychotropic medication. From this context we aimed to evaluate changes in sympathetic arousal using analysis of electrodermal activity (EDA) as an index of sympathetic cholinergic activity in treated and non-treated autistic children under resting conditions.

Methods: We examined 23 children with ASD and 14 healthy age- and gender-matched children at the age of 7–15 years. The ASD patients were divided into ASD non-treated group (n=12) and ASD treated group (n=11). The EDA was continuously monitored during resting phase in a supine position. The EDA amplitude (μS) was computed as an average of 5 min baseline period.

Results: We found significantly lower EDA in ASD non-treated subgroup compared to controls indicating subtle abnormalities in the regulation of the sympathetic nervous system. Although no significant differences were found between the ASD treated and non-treated subgroups the ASD treated group showed comparable sympathetic activity relative to controls indicating a potential ameliorated treatment effect on sympathetic arousal in ASD.

Conclusions: These findings could help to determine differences in sympathetic arousal in treated and non-treated children with ASD, which is important for assessment of autism-linked cardiovascular risk depending on pharmacotherapy.

Open access

K. Javorka, M. Javorka, I. Tonhajzerova, A. Calkovska, Z. Lehotska, Z. Bukovinska and M. Zibolen

Determinants of Heart Rate in Newborns

This paper presents an overview of cardiac chronotropic regulation determinants in newborns, which are reflected in mean heart rate (HR) and heart rate variability (HRV). Heart rate and heart rate variability in newborns are determined by many factors. Heritability and maturation play major role. Factor of the maturation can be seen in HR and HRV differences between healthy full term and preterm newborns as well as in changes over early postnatal time. These parameters in newborns are influenced also by many other factors as gender, nutrition, sleep, breathing pattern/ventilation, etc.

Autoregulation and extrinsic regulation of cardiac activity has its own specificities in newborns. Homeometric mechanism (depended on HR) is dominant and baroreflex sensitivity is reduced, mainly in premature newborns. Complex cardiac regulation can be studied and evaluated by cardiac reflexes. Examination of the reflexes in newborns is limited. Therefore, new approaches for the study of maturation cardiac control are developed taking into consideration all cardiac activity in newborns determinants.

Open access

M. Javorka, I. Tonhajzerova, Z. Turianikova, L. Chladekova, K. Javorka and A. Calkovska

Quantification of Nonlinear Features in Cardiovascular Signals

The analysis of spontaneous heart rate and blood pressure oscillations under standardized conditions is a rapid, sensitive, noninvasive and reproducible tool for the assessment of cardiovascular autonomic dysfunction. Since the heart and vessels are controlled by a nonlinear deterministic system, measures derived from nonlinear systems theory are increasingly used in cardiovascular variability analysis. New nonlinear methods with applicability to real biological signals are continuously developed to quantify new aspects of cardiovascular signals with the potential to reveal subtle changes in the cardiovascular control system. Nonlinear measures provide complementary information about qualitative features of the analyzed signal. Since the analysis of variability magnitude and signal nonlinear characteristics (complexity, recurrences, time irreversibility, etc.) can provide independent information on cardiovascular system control, we suggest that simultaneous use of both groups of measures can increase the information value and thus improve the sensitivity and reliability of the detection and monitoring of the cardiovascular system dysregulation during various pathological conditions.