The Generalized Unsafety Theory of Stress proposes that physiological markers of generalized stress impair learning of safe cues in stressful environments. Based on this model, chronic problems inhibiting physiological arousal lead to a heightened perception of threat, which involves experiencing anxiety symptoms without any obvious precipitating stressful or traumatic event. This investigation aims to determine the impact of stressor- versus context-related emotional learning on generalized unsafety, using a Pavlovian threat-conditioning paradigm. The difference in learning threatening cues ([CS+] paired with an aversive stimulus) compared to safety cues ([CS-] not paired with an aversive stimulus) was used as a proxy measure of generalized unsafety, as conceptualized by the GUTS model. This difference is expected to be moderated by individual differences in tonic cardiac regulation (i.e. heart rate variability). Lastly, a temporal-differences learning model was used to predict skin-conductance learning during stressor, stressor context and general contexts to determine which best predicts Pavlovian learning. TD learning is expected to better predict skin-conductance in individuals with higher fear inhibition in comparison to those with low fear inhibition. / Doctor of Philosophy / This study examined the claims of a theory about how human bodies respond to stress and what this tells us about how anxiety develops in and affects the mind and body. The theory is named the Generalized Unsafety Theory of Stress (GUTS) and two main hypotheses were tested in this study: 1) the theory suggests that a person's feeling of safety is affected by the variation in their heart rate at rest, and 2) that a person's feeling of safety could be observed most accurately by their body's defense responses when they are experiencing a threatening situation that is objectively safe. Individuals experiencing anxiety often report being aware that they are safe, yet their heart rate remains elevated and palms remain sweaty. Most studies that have examined the body's defense response have focused almost solely on reactions to a threat by looking at the reactions of one or more organs that make up the body's defense-response systems (e.g., heart). Results of this study confirmed the unique GUTS perspective. Specifically, the heart rate's variation at rest affects the defense response (sweaty hands) during threatening and objectively safe contexts, which in turn, predicts a person's feeling of safety. These results confirm that there are measurable biological constraints that change the way people learn about and react to their environments, which is very important for understanding the development and maintenance of anxiety physiology and behavior. The way a person learns to associate emotional responses to certain cues in their environment, particularly threat and safety cues, can be measured as defense responses in the body in response to a series of trials. Exploratory analyses examined human threat learning in comparison with mathematically-generated learning in order to better model the processes whereby anxiety develops based on learning of threat and safety cues.

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Inappropriate sinus tachycardia (IST) is a common disease of the autonomic nervous system in children and adults. Diagnosis and treatment of IST in adolescents is not well defined. In this retrospective study, we tested our hypothesis regarding autonomic dysfunction in childhood by analyzing 24-h heart rate variability (HRV) in 479 children, with a mean age of 13.7 ± 2.1 years, who were referred to the outpatient clinic in the Pediatrics Department within the last 15 years. Seventy-four adolescents with a mean 24-h heart rate ≥ 95 bpm (our cut-off for an IST based upon 66 healthy controls) were deemed to have IST. We found the risk of IST to be high in adolescents with attention deficit disorder (OR = 3.5,p<0.001), pre-hypertension (OR = 2.5, p = 0.043) and hypertension (OR = 2.1,p = 0.02); insignificantly enhanced in children with short stature (OR = 1.9,p = 0.19), surgically-treated congenital heart disease (OR = 1.4,p = 0.51) and obesity without hypertension (OR = 1.4;p = 0.25); and negligible in adolescents with anorexia nervosa (OR = 0.3, p = 0.26) and constitutional thinness (OR = 0.9,p = 0.89). IST was associated with a significant decrease in global HRV and elevated blood pressures, indicating an enhanced cardiovascular risk. Methylphenidate did not increase 24-h heart rates, whereas omega-3 fatty acid supplementation significantly decreased elevated heart rates and increased HRV in adolescents with IST. In this retrospective analysis, 15.4% of adolescents suffered from IST with a 24-h heart rate ≥ 95 bpm, predominately due to attention deficit disorder and hypertension. / Die Inadäquate Sinustachykardie (IST) ist eine häufige Erkrankung des autonomen Nervensystems bei Kindern und Erwachsenen. Die Diagnose und Therapie einer IST bei Jugendlichen ist bisher nicht genau definiert. In dieser retrospektiven Studie haben wir unsere Hypothese bezüglich autonomer Dysfunktion im Kindesalter durch die Analyse von 24-h Herzfrequenzvariabilität (HRV) bei 479 Kindern mit einem Durchschnittsalter von 13,7 ± 2,1 Jahren, die innerhalb der letzten 15 Jahre an die pädiatrische Ambulanz überwiesen wurden, untersucht. 74 Jugendliche hatten eine mittlere Herzfrequenz ≥95/min (Cut-off Werte für eine IST basieren auf der gesunden Kontrollgruppe) und hatten damit eine IST. Wir stellten fest, dass das Risiko einer IST bei Jugendlichen mit einer Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) (OR = 3,5, p < 0,001), Prä-Hypertonie (OR = 2,5, p = 0,043) und Hypertonie (OR = 2,1, p = 0,02) hoch ist; nicht signifikant erhöht bei Kindern mit Kleinwuchs (OR = 1,9, p = 0,19), chirurgisch behandelte angeborene Herzkrankheit (OR = 1,4). ,p = 0,51) und Adipositas ohne Bluthochdruck (OR = 1,4; p = 0,25); und unbedeutsam bei Jugendlichen mit Anorexia nervosa (OR = 0,3, p = 0,26) und konstitutioneller Dünnheit (OR = 0,9, p = 0,89). Eine IST war mit signifikant reduzierten HRV-Werten und erhöhten Blutdrücken assoziiert, was auf ein erhöhtes kardiovaskuläres Risiko hindeutet. In dieser retrospektiven Analyse litten 15,4 % der Jugendlichen an einer IST mit einer 24h HF ≥ 95 bpm hauptsächlich aufgrund einer ADHS und Hypertonie.

Rates of depression, anxiety, and stress have been increasing and college students are especially at risk. College counseling centers often have long waitlists and have difficulty addressing the growing need for psychotherapy. Researchers have suggested that depression and anxiety may arise because of low levels of eudaimonia and self-compassion. Depression and anxiety not only have a toll on mental health but on physical health as well, as researchers have observed decreased HRV in individuals with depression and anxiety. To address the disparity between available resources and treatment need, applied mental health classes were developed to see if teaching psychotherapeutic principles in the classroom setting would lead to decreases in depression, anxiety, stress, and improvements in eudaimonia, gratitude, self-compassion, and HRV. Data was collected from students in the applied mental health classes and were compared to a control group of students who were not in those classes. HRV was measured twice (beginning and end of the academic semester), and questionnaire data was collected three times (beginning, middle, and end of the academic semester). A total of 44 students (86% female) were recruited from the applied mental health classes with 34 completing the whole study and 190 students (62% female) were recruited for the control group with 76 completing the study. SEM was used to analyze change across time for each of these variables. There were not significant changes in distress, eudaimonia, gratitude, self-compassion, or HRV across the semester in both the experimental and control group. More specifically, the students in both the applied mental health class and control group were not significantly distressed at baseline and had high HRV. There were many ceiling and floor effects in this sample which left little room for improvement. Testing this class in a more distressed sample will help elucidate the impact that these classes can have.

At the time of writing, stress and stress related disease have become the most common reasons for absence in the workplace in Sweden. The purpose of the work presented here is to identify and notify people managing unhealthy levels of stress. Since symptoms of mental stress manifest through functions of the Sympathetic Nervous System (SNS), they are best measured through monitoring of SNS changes and phenomena. In this study, changes in the sympathetic control of heart rate were recorded and analyzed using heart rate variability analysis and a simple runner’s heart rate sensor connected to a smartphone. Mental stress data was collected through stressful video gaming. This was compared to data from non-stressful activities, physical activity and extremely stressful activities such as public speaking events. By using the period between heartbeats and selecting features from the frequency domain, a simple machine learning algorithm could differentiate between the types of data and thus could effectively recognize mental stress. The study resulted in a collection of 100 data points, an algorithm to extract features and an application to continuously collect and classify sequences of heart periods. It also revealed an interesting relationship in the data between different subjects. The fact that continuous stress monitoring can be achieved using minimally intrusive sensors is the greatest benefit of these results, especially when connsidering its potential value in the identification and prevention of stress related disease.

Title:  Will you cope, without your family? – The importance of support for youths who are subject to honour related violence.   The aim of this study has been to examine which support has been given to the youths who have been subjected to honour related violence and their experiences about the support. The data were collected through four semi-structured, qualitative interviews with youths who had separated from their families. The result showed that according to an intersectional perspective the individual needs should dictate the support offered and that honour related violence is a complex problem. System theory, shows us that it is important to belong to a family system, whether it is biological or not – is of less importance. The social services and the foster homes are important for the youths in their efforts to cope without their families Based on the results, our conclusion is that many need a lot of therapy in order to return to a “normal life”. / Orkar du, utan din familj? – Betydelsen av stödinsatser till ungdomar som är utsatta för hedersrelaterat våld och förtryck. Studiens syfte var att undersöka vilket stöd, ungdomar som blivit utsatta för hedersrelaterat våld och förtryck (HRV), fått samt deras upplevelse av detta. Data samlades in genom fyra semistrukturerade, kvalitativa intervjuer med ungdomar som har haft ett uppbrott från sin biologiska familj. Resultatet visade att enligt intersektionellt perspektiv bör individuella behov styra det erbjudna stödet och att HRV är ett komplext problem. Systemteorin ger oss förståelse för familjens betydelse och vikten av att tillhöra ett familjesystem, biologiskt eller inte är av mindre betydelse. Både socialtjänsten och familjehemmen är viktiga för ungdomarna i deras strävan att orka utan sina familjer. Utifrån resultatet är vår slutsats att det för många krävs mycket samtalsstöd för att återgå till ett ”normalt liv”.

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Bioelectronic medicine is an emerging discipline being a intersection of neu- roscience, immunology and electrical engineering. Chronic inflammation is linked to disorders such as diabetes, rheumatoid arthritis, asthma, atheroscle- rosis, obesity and inflammatory bowel disease. Chronic inflammatory diseases have been recognized as the most significant cause of death in the world today, with more than 50% of all deaths being attributable to inflammation-related diseases. To find specific parameters for the stimulation of the vagus nerve would be a major advancement in the field, since it will help restore the vagal tone optimally. A systematic review has been made to understand and explore the tissue damage, stimulation sites, FDA approved parameters and the safety and efficacy in vagus nerve stimulation (VNS). A control closed- loop system was developed based on the needs of the field and a human clinical trial protocol was proposed.    The control close-loop system is able to receive feedback from a continuous real-time measurement of the pressure of the peripheral blood flow and send a VNS based on a heart rate (HR) settled threshold. The stimulation is delivered with previously settled parameters such as, pulse width, output current, duty cycle and frequency and helps observe if the nerve has been correctly targeted or not. From the results, it becomes clear that the connection of the devices has been correctly accomplished and that the HR reduction is being measured by the control close-loop which would stimulate again when the HR threshold is surpassed. Based on the concept of this control close-loop a human protocol has been proposed to test if the hypothesis that patients have their best inflammatory response with different output current rather than all having one best performing one and that non-healthy patients will lower their HR baseline after VNS treatment showing the increase of vagus nerve activity. This report adds value on the creation of a new control close-loop device between the MouseOx and Intan devices. Controlling the stimulation parameters in VNS can be a powerful technique that will increase patient specificity and will help non respondents to different drug treatments to have a more effective alternative. The HR is a simple biomarker to detect VNS bioactivity but lots of further research on non-invasive devices and software limitations are still needed to be overcome to have clear guidance in the field. The proposal of a new human clinical trial that might give a clear and feasible solution to either find an efficient stimulation setting or the assurance of the real need for an interactive control close-loop system that would tailor the stimulation parameters for each specific patient is presented. / Bioelektronisk medicin är en framväxande disciplin som är en skärningspunkt mellan neurovetenskap, immunologi och elektroteknik. Kronisk inflamma- tion är kopplad till sjukdomar som diabetes, reumatoid artrit, astma, åder- förkalkning, fetma och inflammatoriska tarmsjukdomar som är den vanligaste dödsorsaken i världen idag. Att hitta specifika parametrar för stimulering av vagusnerven skulle vara ett stort framsteg på området, eftersom det hjälper till att återställa vagustonen optimalt. En systematisk översyn har gjorts för att förstå och utforska vävnadsskadan, stimuleringsställena, FDA-godkända parametrar och säkerheten och effekten i VNS. Ett kontrollsystem med slutet kretslopp utvecklades baserat på fältets behov och ett protokoll för kliniska prövningar för människor föreslogs. Kontrollsystemet kan ta emot feedback från en kontinuerlig realtidsmätning av trycket i det perifera blodflödet och skicka en VNS baserat på en HR-bestämd tröskel. Stimuleringen levereras med tidigare inställda parametrar såsom pulsbredd, utström, arbetscykel och frekvens. Av resultaten blir det tydligt att anslutningen av enheterna har åstadkommits korrekt och att HR-reduktionen mäts av kontrollens slutslinga som skulle stimulera igen när HR-tröskeln överskrids. Baserat på konceptet med denna kontroll close-loop har ett mänskligt protokoll föreslagits för att testa om hypotesen att patienter har sitt bästa inflammatoriska svar med olika utström snarare än att alla har en bäst presterande och att icke-friska patienter kommer att sänka sin HR baslinje efter VNS-behandling som visar ökningen av vagusnervens aktivitet. Den här rapporten ger ett mervärde när det gäller skapandet av en ny kontrollenhet mellan MouseOx- och Intan-enheterna. Att kontrollera stimuleringsparametrarna i VNS kan vara en kraftfull teknik som kommer att öka patientspecificiteten och som hjälper icke-respondenter till olika läkemedelsbehandlingar att få ett mer effektivt alternativ. HR är en enkel biomarkör för att upptäcka VNS-bioaktivitet, men massor av ytterli- gare forskning om icke-invasiva enheter och mjukvarubegränsningar behövs fortfarande för att få en tydlig vägledning på området. Förslaget om en ny klinisk prövning på människa som kan ge en tydlig och genomförbar lösning för att antingen hitta effektiva stimuleringsmiljöer eller försäkran om det verkliga behovet av ett interaktivt kontrollsystem med nära slinga som skulle skräddarsy stimuleringsparametrarna för varje specifik patient presenteras.