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Die häufigste primäre Kopfschmerzerkrankung ist der im Vergleich zur Migräne wenig untersuchte Spannungskopfschmerz (engl: tension-type headache). Als pathophysiologische Ursachen werden emotionale Störungen, Stress und Depressionen vermutet. In klinischen Studien wurde mehrfach eine Komorbidität von Spannungskopfschmerzen mit Depressionen und Angststörungen gefunden. Epidemiologische, bevölkerungsbezogene Untersuchungen zur Assoziation von Depressionen und Angststörungen zum Spannungskopfschmerz sind hingegen rar. Ziel der vorliegenden Arbeit war es auf der Grundlage einer bevölkerungsbezogenen breitangelegten Studie eine Assoziation von Symptomen der Depressionen und Angststörungen zu Spannungskopfschmerzen zu prüfen. Die Arbeit basiert auf der ersten Folgeuntersuchung der SHIP (Study of Health in Pomerania) mit 3300 Probanden, deren Daten zwischen 2002 und 2006 erhoben wurden. Als Vergleichsgrundlage wurde die Prüfung einer Assoziation der Migräne zu Depressionen und Angststörungen herangezogen. Da der Spannungskopfschmerz in chronischer und episodischer Form auftritt, und es Hinweise auf kopfschmerzartunabhängige Zusammenhänge von psychischen Faktoren und chronischen Kopfschmerzen gibt, wurde der Aspekt der Kopfschmerzchronizität ebenfalls mitbetrachtet. Als potentielle Confounder gingen soziodemographische Faktoren, Variablen chronischer Erkrankungen, Variablen des Alkohol- und Tabakkonsums sowie Symptome der Depressionen und der Angststörungen untereinander in diese Arbeit ein. Für den Spannungskopfschmerz zeigte sich keine unabhängige Assoziation von Symptomen der Depressionen oder Angststörungen, wohingegen sich für die Migräne (OR: 1,8 (95%-KI: 1,15 - 2,83)) und den chronischen Kopfschmerz (OR: 3,06 (95%-KI: 1,34 - 6,98)) eine unabhängige Assoziation zu depressiven Symptomen darstellen ließ. Allerdings fand sich in einem zusätzlich berechneten logistischen Regressionsmodell des Spannungskopfschmerzes ein unabhängig signifikant erhöhtes OR der Variable „Angststörungen“ (OR: 1,3 (95%-KI: 1,04 – 1,62)), wenn nicht für Depressionen, aber für alle anderen potentiellen Confounder adjustiert wurde. Dieses Ergebnis führt vor dem Hintergrund einer anzunehmenden hohen Komorbidität von Angst- und Depressionsstörungen zur Annahme, dass ein erhöhtes Risiko für Spannungskopfschmerzen bei Vorliegen von „nicht unabhängig voneinander bestehenden angst- und depressionsbezogenen Symptomen“ bestehen könnte. Ob dies tatsächlich nachweisbar ist, müssen weitere Untersuchungen klären. Für einen Fortschritt im ätiologischen Verständnis primärer Kopfschmerzerkrankungen, insbesondere des Spannungskopfschmerzes, sollten zudem zukünftig longitudinale Studien eine wesentliche Rolle spielen.
Body sensations play a crucial role in the etiology and maintenance of diverse anxiety and health problems (e.g., in panic disorder or respiratory diseases) as they may be perceived as threatening and consequently elicit anxious responses. The factors that may affect the perception of bodily sensations as a threat and thus modulate the anxious response to body sensations have so far rarely been studied. Therefore, the present thesis targeted at elucidating the effect of contextual (i.e., the predictability, expectation, and proximity of a threat) and dispositional factors (i.e., tendency to fear arousal sensations or trait fear of suffocation) on the defensive response to body sensations.
In study 1, it was investigated how a personality factor, that is, fear of suffocation, affects the acquisition of fear to body sensations (i.e., mild dyspnea induced by inspiratory resistive loads) and contexts when faced with a predictable and unpredictable respiratory threat (i.e., severe dyspnea). Study 2 aimed at examining the main and interactive effects of the tendency to fear arousal sensations, again a personality trait factor, and current arousal expectations as varied by situational variables on anxious responding to arousal sensations. In this study, expected and unexpected arousal sensations were induced by administering caffeine in coffee or bitter lemon soda, respectively. Moreover, in study 3, it was explored how subjective anxiety, bodily symptoms, and defensive respiratory responses change and might culminate into active defense behavior (i.e., escape/active avoidance) during increasing dyspnea that was evoked by inspiratory resistive loads increasing in intensity. For a detailed analysis of the factors that contribute to the initiation and maintenance of avoidance of or escape from increasing dyspnea, in study 4 changes in subjective, autonomic, somatic reflex and brain responses were analyzed during repeated avoidance of increasing dyspnea.
In study 1, it was demonstrated that only individuals who fear suffocation learned to fear mild dyspnea preceding the onset of severe dyspnea and developed anxiety during a context of unpredictable respiratory threat. Moreover, the data from study 2 indicate that individuals who fear arousal sensations show an increased attention allocation towards unexpected arousal sensations and higher threat appraisal when expecting arousal sensations. Increasing intensity of dyspnea as provoked in study 3 led to increased defensive respiratory responses that were associated with increased symptom reports in individuals with high compared to low fear of suffocation. Moreover, culminating dyspnea elicited repeated avoidance behavior preceded by increases in defensive respiratory mobilization. The analysis of repeated avoidance of increasing dyspnea in study 4 revealed that physiological fear responses might be involved in the initial initiation of this avoidance behavior while no indication of response preparation and physiological arousal was related to persistent avoidance.
Taken together, the present data suggest that the fear of suffocation, as well as the tendency to fear arousal sensations along with the predictability, expectation, or proximity of interoceptive threat, may increase the perceived threat and thus the anxious response to body sensations. Therefore, contextual and dispositional factors may set the stage for the culmination of body sensations into defensive action and might contribute to the development of pathological anxiety and fear of body sensations. The present findings are integrated into the current literature and discussed in relation to the development and maintenance of pathological anxiety and fear of body sensations.
Fear is an emotional state, characterized by the activation of a defense system that is designed to ensure the organism’s survival. This system enables a rapid recognition of threats and organizes defensive response patterns in order to adaptively cope with the threatening environment. Yet, to ensure its flexibility under changing environmental conditions, inhibitory pathways exist that modulate the activation of this defense system, if a previously threatening cue no longer predicts any harm – a memory-formatting process referred to as fear extinction, leading to a reduction of defensive responding. Fear extinction is presumed to at least partially underlie exposure treatment of anxiety disorders, which is why the facilitation of this learning process may promote such treatment’s efficacy. Animal models suggested, that the stimulation of the vagus nerve or the superior colliculus (SC) – a midbrain structure mediating visual attentional processing – target these inhibitory extinction pathways and, thus, facilitate fear extinction. However, as it is unclear whether similar mechanisms exist in humans, this thesis manuscript examined how non-invasive stimulation of these inhibitory pathways by transcutaneous vagus nerve stimulation (tVNS) or SC-recruiting visual attentional manipulation impact on human fear extinction.
To this end, we conducted three studies using multiple-day single-cue fear conditioning and extinction paradigms. First, we elaborated on fear that is established in these paradigms by examining defensive responding that is elicited by an innocuous conditioned stimulus, which has either been paired (fear learning group) with an aversive unconditioned stimulus (US; an electric shock) or was unpaired (control group; study 1). During the following extinction training, either tVNS vs. sham stimulation was applied (study 1, study 2) or participants were instructed, to either generate saccadic eye movements (strong SC activation) vs. smooth eye pursuits (low SC activation; study 3). During subsequent sessions, extinction consolidation as well as the short- and long-term extinction recall was tested (study 2, study 3).
Conditioned fear in the fear learning group was characterized by elevated cognitive risk assessments (US-expectancy ratings), as well as increased cardiac deceleration and startle reflex potentiation compared to controls. Cardiac deceleration was positively correlated to startle potentiation, but was decoupled from cognitive risk assessments (study 1). Initial, short- and long-term extinction of these defensive responses was facilitated by tVNS on all three response levels (cognitive, physiological, behavioral; study 1, study 2). In contrast, saccades facilitated initial extinction only for physiological and behavioral elements of the defensive response pattern, while extinction consolidation and recall was impaired by any eye movement manipulation (study 3) for physiological and behavioral indicators of defensive responding.
Taken together, the data of the experimental series suggest, that on a behavioral level, conditioned fear may best be conceived as attentive immobility – a defense strategy elicited by inevitable distal threats, that is uniformly expressed across species and is accompanied by cardiac deceleration and startle reflex potentiation. In addition, it was shown that such rather automatic defensive adaptations are independent from verbally expressed threat expectancies. As expected, tVNS impacted on fear extinction on both levels, strongly in line with the suggestion, that vagal stimulation activates cortical and subcortical neural pathways involved in extinction learning, consolidation and recall. TVNS may, thus, be a promising adjuvant for exposure treatment of mental disorders. In contrast, SC-recruiting visual attentional manipulation only affected subcortically mediated defensive responding, in line with rodent findings, indicating that the SC specifically inhibits subcortical parts of the neural defense system. However, as extinction recall was impaired by any type of visual attentional manipulation, this appeared to have functioned as a form of avoidance, initially attenuating fear but preventing extinction consolidation and, thus, impairing sustained fear reduction. Both non-invasive stimulation techniques may therefore increase initial defensive flexibility in the face of no-longer threat-signaling stimuli, but only tVNS may achieve long-term effects on multiple response levels.