Depressive Störungen sind Erkrankungen mit hoher Prävalenz und weitreichenden Beeinträchtigungen für das Leben Betroffener, sie bergen Risiken für Rezidive und Chronifizierung. Eine Vielzahl diagnostischer und therapeutischer Verfahren und Methoden steht zur Verfügung, um depressiven Patienten zu helfen, doch erreicht diese Hilfe längst nicht alle. Die digitale Revolution und der Einzug mobiler Geräte wie Smartphones oder tragbarer Sensorgeräte in den Alltag eröffnen neue Möglichkeiten und Wege sich diesen Herausforderungen für die Behandlung depressiv Erkrankter zu stellen. Der Markt an Apps für das Selbst-Monitoring und das Krankheitsmanagement bei Depression wächst beständig, doch ob und in welchem Umfang Depressive solche Angebote wahrnehmen ist wenig erforscht. Die vorliegende Arbeit zu Präferenzen und Wünschen potentieller Nutzer versucht hier Antworten zu finden. Mobile Systeme aus Smartphones, Apps und tragbaren Sensoren können einen Beitrag zum Krankheitsmanagement bei Depression leisten und so die Versorgung Erkrankter verbessern. Mit Hilfe solcher Geräte und Apps lassen sich subjektive oder objektive Daten messen, verarbeiten, evaluieren und für Selbstmanagement, Diagnose und Therapie nutzbar machen. Kontinuierlich im Lebensalltag erhobene objektive Daten wie Bewegung, Aktivitäten, Schlaf als auch physiologische Parameter wie Hautleitfähigkeit oder Herzaktivität sind von unschätzbarem Wert, um Patienten frühzeitig auf Symptome, Wahrnehmungs- und Verhaltensveränderungen aufmerksam zu machen. Die Untersuchung der Veränderungen in der Herzfrequenz (Heart Rate Varibitly, HRV) und depressiven Symptomen stellt einen wichtigen Ansatz für die Suche nach reliablen Bio-Markern für Depression dar. Um objektiven Bioparametern wie HRV in Zukunft in mobilen Systemen zum Selbst-Monitoring und individuellen Krankheitsmanagement bei Depression einsetzen zu können ist aber ein besseres Verständnis der Zusammenhänge zwischen beiden nötig. Die vorliegende Arbeit versucht, weitere Einsicht in den Zusammenhang zwischen Veränderungen in der HRV und dem Krankheitszustand bei Depression zu liefern.:Einführung S5 Publikationsmanuskript 1 S15 Publikationsmanuskript 2 S23 Zusammenfassung S31 Literaturverzeichnis S32 Appendix S43 Darstellung des eigenen Beitrags S44 Selbstständigkeitserklärung S46 Publikationen und Vorträge S47 Danksagung S48

The study dealt with the influence of exercise on the autonomic nervous system (ANS) and with factors that may influence the results. ANS function was measured in 183 young, healthy participants, before and after a twelve week standardised, medium-to-high volume physical training programme, in a controlled environment. The effects of the training programme were assessed on resting ANS functioning, during standing and on the response to an orthostatic challenge. ANS function was assessed by means of heart rate variability (HRV) determination. HRV was quantified by three different analytical techniques, i.e., time domain analysis (RR, STDRR, RMSSD and pNN50), frequency domain analysis (LF,LFnu, HF, HFnu and LF/HF) and Poincaré plot analysis (SD1 and SD2). The influence of technical variations, such as variations in tachogram length and period of recording, as well as the influence of pre-intervention values of physiological variables, such as blood pressure, BMI, VO2 max and ANS functioning, on the response to the exercise intervention, were assessed. Results on the exercise intervention showed: <ul><li> Increased supine, as well as standing, parasympathetic cardiac control as indicated by time domain, frequency domain and Poincaré analyses. </li><li> Decreased sympathetic control in the supine position and increased sympathetic control during rising and standing. </li><li> Increased vagal withdrawal, as well as increased sympathetic control during the first phase of the orthostatic response to rising from the supine position. </li><li> Only an exercise-induced increase in sympathetic control when the orthostatic response was measured as the difference between standing and supine. </li></ul> Results on exercise-induced changes in sympathetic and parasympathetic ANS control differ, depending on posture. It is suggested that the effects of an exercise intervention on sympathetic and parasympathetic ANS control of the heart should be assessed from measurements in the supine, in the standing, and in response to an orthostatic stressor. It is further suggested that information obtained during rising will give additional information on the response of the ANS. This study showed that technical as well as physiological variations may lead to differences in the outcome of HRV studies. Results from the technique evaluation showed that the length and period of tachogram recordings should be standardised, especially during an orthostatic challenge. Starting the recording too late will miss out on the initial response to a change in body position. Longer recording times will represent the mean of HRV values obtained during the orthostatic response and that obtained after stabilisation in the standing position. Investigations into the influence of pre-intervention physiological status on exercise-induced changes showed: <ul><li> Baseline ANS functioning is a significant contributor to variations in the ANS response to an exercise intervention. </li><li> Pre-intervention values for physiological variables, such as blood pressure, BMI and VO2 max do not have a significant influence on the HRV response to exercise in young, healthy individuals of average fitness</li><li> Regression analyses confirm the correlation results, i.e. that baseline ANS function is a significant predictor of the ANS response to exercise. </li><li> However, regression results indicated that the combination of pre-intervention values for LFms2, HFms2, BMI, VO2 max, gender and blood pressure, contributes only between 12.83% and 29.82%, depending on the HRV variable, to the exercise induced changes in the autonomic nervous system. </li></ul> / Thesis (PhD)--University of Pretoria, 2011. / Physiology / unrestricted

<div> <div> <div> <p>Major depressive disorder (MDD) and risk for its development are characterized by reduced reactivity and flexibility to environmental demands. Frontal alpha asymmetry (FAA), heart rate variability (HRV), and salivary cortisol reactivity are each well-established indicators of regulation across neural, autonomic, and hypothalamic-pituitary-adrenal (HPA) physiological systems, respectively. Growing literature suggests that each of these processes is dysregulated in individuals with a history of MDD. However, patterns of dysregulation across these physiological systems and relative MDD risk are unknown. Moreover, these physiological regulatory patterns may extent beyond markers of MDD risk in adulthood to also capture the transmission of risk for MDD from parent to offspring. The following series of five studies investigated the pathophysiology of MDD and the permeability of risk across the lifespan. First, the pattern of dysregulation across physiological indices—representing neural, autonomic, and HPA functioning—in adults was examined with regard to depressive symptoms. Second, the associations amongst infant FAA, HRV, and cortisol reactivity and maternal depressive symptoms were assessed as potential early markers of depression risk. Third, mother-infant associations across physiological indices were investigated to assess direct intergenerational transmission of depression risk. Studies 4 and 5 further investigated pathophysiological functioning in mothers and infants within the context of comorbid anxiety and current depressive symptomatology versus lifetime MDD illness. Mothers and their 12-month-old infants (n = 35 dyads) completed resting- state and stressor tasks to assess regulatory patterns across neural, autonomic, and HPA systems, associations with MDD, and intergenerational transmission. In adults, results suggest that lifetime history of MDD is significantly associated with blunted cortisol reactivity; FAA and high- frequency HRV also demonstrated the same direction of associations. In infants, results demonstrated that maternal depressive symptoms, particularly current symptoms, relate to blunted physiological regulation in infants specifically for FAA and HRV indices. For mothers and infants, there was support for the direct intergenerational transmission of FAA and HRV indices. These intergenerational associations did not fully account for intergenerational risk of depression, as maternal physiological regulation and maternal depression were found to each significantly predict infant regulation as simultaneous predictors. Accounting for comorbid anxiety and examining current symptoms versus lifetime illness were essential to investigating associations amongst physiological functioning and depression. These patterns in conjunction with the literature suggest a developmental model to MDD pathophysiology that encompasses multiple theoretical frameworks. Future research is necessary to clarify regulatory patterns across physiological systems within individuals and across time with regard to MDD risk, onset, and course.</p></div></div></div>

Heart Rate Variability (HRV) is a medical term describing the heart’s natural varying time difference between heartbeats (called NN-intervals). A higher HRV i.e. a larger variability between NN-intervals is connected to healthiness, and lower HRV to unhealthy states. Biofeedback (BF) is a method that can detect and send physiological signals back to the user on a screen. Every individual has a resonant frequency, and when breathing at this frequency, the interplay between blood pressure and respiration causes HRV to increase momentarily. HRV biofeedback aims at increasing HRV, by measuring heart rhythm and respiration to guide the user in resonant breathing. This thesis had the objective to investigate the effectiveness of one 20 minutes long biofeedback session with resonant frequency breathing. The hypothesis was that the time frame would be longer than two hours. It was carried out with 12 healthy volunteers, who participated in a biofeedback session with an Android application, and afterwards 5 minutes long ECG measurements were made every half hour for two hours. A control session was held with the same participants to give the trial more scientific strength. The result showed that a 20 min resonant breathing biofeedback session can elevate Standard Deviation of NN intervals (SDNN) significantly (p &lt; 0.05), 2 hours after the biofeedback session. The conclusion was that the hypothesis cannot be rejected, but the result is too weak to strengthen it much. Further research is needed to draw more conclusions about the time frame of HRV elevations in healthy people.

Previous research suggests that attentional deficits could be the underlying cause of language impairments in people with aphasia (PWA) and that behavioral engagement ratings can be an accurate way to measure attention to specific tasks. Previous research also suggests that PWA have lower levels of behavioral engagement than neurologically healthy adults. Participants in the present study included 9 PWA and 18 neurologically healthy adults. This was an exploratory study investigating the relationships and differences between behavioral engagement and physiological measures, perceived arousal, and naming accuracy and response time in PWA and neurologically healthy adults. Participants completed a confrontational naming task while physiological measures (heart rate, heart rate variability, and skin conductance) were taken simultaneously. Subsequent video footage was used to rate participants' behavioral engagement (i.e., how engaged the participant was in the naming task). In general, PWA had lower behavioral engagement ratings of attention than neurotypical adults. Significant correlations were found between behavioral engagement ratings of attention, naming response time, and naming accuracy. No statistical significance was found between behavioral engagement ratings of attention and heart rate, heart rate variability, and skin conductance. Further research is needed to support these findings.

The cognitions of individuals who experience symptoms of depression, anxiety, and stress have been well documented, but their physiological reactions have not. The present study examines the physiological reactions of individuals with elevated levels of depression, anxiety, and stress during a self-critical and self-compassionate writing exercise to see if there is a difference in comparison to healthy participants. This study is a secondary analysis of data that was collected from a randomized controlled trial where participants followed a protocol. This protocol consisted of a 5-minute baseline, a 10-minute breathing exercise or nature video, 5-minutes of a self-critical writing exercise, 5-minutes of a self-compassionate writing exercise, and a 10-minute recovery period. The individuals in the study were separated into different groups depending on their scores on a measure of depression, anxiety, and stress. The data were analyzed twice with two different grouping methods. One method compared individuals with mild to severe symptoms of depression (35 individuals), anxiety (43 individuals), and stress (33 individuals) to healthy group (26 individuals) and another method compared individuals with moderate to severe symptoms of depression (28 individuals), anxiety (36 individuals), and stress (24 individuals) to 44 healthy individuals. In both methods, the participants with symptoms of depression, anxiety, and stress did not significantly differ from healthy participants on any measure of HRV (e.g., SDNN, LF HRV, HF HRV). Overall, the results of this show that college students with symptoms of depression, anxiety, and stress physiologically react in a similar way to a self-critical and self-compassionate writing exercise.

In nature we find many instances of complex behavior for example the dynamics of stock markets, power grids, internet networks, highway traffic, social networks, heartbeat dynamics, neural dynamics, dynamics of living organisms, etc. The study of these complex systems involves the use of tools of non-linear dynamics and non-equilibrium statistical physics. This dissertation is devoted to understanding two different sources of complex behavior – non-poissonian renewal events also called crucial events and infinite memory of fractional Brownian motion. They both generate 1/f noise frequency spectrum. Thus, we studied examples of both processes and also their joint action. We also tried to establish the role of crucial events in biological and physiological processes like biophoton emission during the germination of seeds, the dynamics of heartbeat and neural dynamics. Using a statistical method of analyzing the time series of bio signals we were able to quantify the complexity associated with the underlying dynamics of these processes. Finally, we adopted a model that unifies both crucial events and memory fluctuations to study the rhythmic behavior observed in heart rate variability of people during meditation. We were able to also quantify the level of stress reduction during meditation. The work presented in this dissertation may help us understand the communication and transfer of information in complex systems.

The scope of cardiac pathophysiology in sepsis has not been fully defined. Accordingly, we evaluated the effects of sepsis on heart rate (HR), HR variability, and conduction parameters in a murine model of sepsis. Electrocardiograms were recorded noninvasively from conscious mice before and after cecal ligation and puncture (CLP) or sham surgery. Responses of isolated atria to tyramine and isoproterenol were quantified to assess the functional state of sympathetic nerves and postjunctional sensitivity to adrenergic stimulation. Cecal ligation and puncture mice had lower HR compared with sham at 16 to 18 h postsurgery (sham, 741 ± 7 beats/min; CLP, 557 ± 31 beats/min; n = 6/group; P < 0.001), and there was significant prolongation of the PR, QRS, and QTc intervals. Slowing of HR and conduction developed within 4 to 6 h after CLP and were preceded by a decrease in HR variability. Treatment of CLP mice with isoproterenol (5 mg/kg, intraperitoneally) at 25 h after surgery failed to increase HR or decrease conduction intervals. The lack of in vivo response to isoproterenol cannot be attributed to hypothermia because robust chronotropic and inotropic responses to isoproterenol were evoked from isolated atria at 25°C and 30°C. These findings demonstrate that impaired regulation of HR (i.e., reduced HR variability) develops before the onset of overt cardiac rate and conduction changes in septic mice. Subsequent time-dependent decreases in HR and cardiac conduction can be attributed to hypothermia and would contribute to decreased cardiac output and organ perfusion. Because isolated atria from septic mice showed normal responsiveness to adrenergic stimulation, we conclude that impaired effectiveness of isoproterenol in vivo can be attributed to reversible effects of systemic factors on adrenergic receptors and/or postreceptor signaling.

This study investigated the experiences of clients who completed a brief heart rate variability biofeedback protocol. The purposes of this study were to (1) learn about client experiences of biofeedback because almost no previous research has done so and (2) explore the potential role of common factors in biofeedback. Fifteen clients were interviewed and their data analyzed according to the methods of Consensual Qualitative Research (CQR; Hill, 2012). CQR relies on the use of group consensus to construct representations of participant experiences and categorize themes within the data. The results of the study showed that participants generally experienced the HRVB+ protocol as helpful. They typically expressed that the intervention helped them with their anxiety or stress and that it increased their self-efficacy concerning their ability to manage anxiety or stress. Several domains emerged that captured data about the biofeedback therapist. Though more research is undoubtedly needed, the findings of this study provide some preliminary support for the idea that common factors could play a role in biofeedback interventions.

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