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Die Wirksamkeit und der Nutzen von Psychotherapie sind vielfach nachgewiesen. Dennoch sind die der Psychotherapie zugrunde liegenden Wirk- und Veränderungsmechanismen zu einem großen Teil noch ungeklärt und werden kontrovers diskutiert. Ein vielversprechendes Untersuchungsdesign zur Überprüfung der Wirksamkeit und Wirkungsweise spezifischer psychotherapeutischer Techniken stellt die Untersuchung psychotherapeutischer Mikrointerventionen dar. In der vorliegenden Arbeit wurde ein laborexperimentelles Untersuchungsdesign zur Überprüfung der Wirksamkeit spezifischer psychotherapeutischer Techniken und damit einhergehender hirnphysiologischer Veränderungen erstmalig erprobt. Untersucht wurden die Effekte einer 90-minütigen psychotherapeutischen Mikrointervention, in der die Technik des kognitiven Reframings vermittelt und eingeübt wurde. Probanden einer subklinisch depressiven Stichprobe (N=45) sowie gesunde Kontrollpersonen (N=47) wurden randomisiert entweder der Mikrointervention oder einer von zwei Kontrollbedingungen zugeordnet. Die Überprüfung der interventionssezifischen Effekte erfolgte über die Erfassung ereigniskorrelierter Potenziale (EKPs) sowie Affekt-Ratings der Probanden. In einem spezifischen EEG-Paradigma wurden den Probanden negativ affektive Bilder gezeigt, die sie entweder aus einem neuen, positiven Blickwinkel betrachten oder nur anschauen sollten. Am Ende jedes Durchganges wurden die Probanden aufgefordert die Intensität ihrer emotionalen Reaktion einzuschätzen. Die Ergebnisse zeigen, dass die Psychotherapeutische Mikrointervention zu spezifischen Effekten, insbesondere auf der Ebene elektrokortikaler Veränderungen führte. Dabei wiesen die Probanden der Gruppe mit der psychotherapeutischen Mikrointervention größere mittlere frontale LPP Amplitudenwerte in Folge der Instruktionsbedingung "Umdeuten" auf. Die Ergebnisse werden im Sinne einer intensivierten kontrollierten Nutzung relevanter, über den präfrontalen Kortex vermittelter, kognitiver Verarbeitungsressourcen im Zusammenhang mit der Herunterregulierung emotionaler Reaktionen interpretiert.
Stress and pain are common experiences in human lives. Both, the stress and the pain system have adaptive functions and try to protect the organism in case of harm and danger. However, stress and pain are two of the most challenging problems for the society and the health system. Chronic stress, as often seen in modern societies, has much impact on health and can lead to chronic stress disorders. These disorders also include a number of chronic pain syndromes. However, pain can also be regarded as a stressor itself, especially when we consider how much patients suffer from long-lasting pain and the impact of pain on life quality. In this way, the effects of stress on pain can be fostered. For the generation and manifestation of chronic pain symptoms also learning processes such as classical conditioning play an important role. Processes of classical conditioning can also be influenced by stress. These facts illustrate the complex and various interactions between the pain and the stress systems. Both systems communicate permanently with each other and help to protect the organism and to keep a homeostatic state. They have various ways of communication, for example mechanisms related to endogenous opioids, immune parameters, glucocorticoids and baroreflexes. But an overactivation of the systems, for example caused by ongoing stress, can lead to severe health problems. Therefore, it is of great importance to understand these interactions and their underlying mechanisms. The present work deals with the relationship of stress and pain. A special focus is put on stress related hypocortisolism and pain processing, stress induced hypoalgesia via baroreceptor related mechanisms and stress related cortisol effects on aversive conditioning (as a model of pain learning). This work is a contribution to the wide field of research that tries to understand the complex interactions of stress and pain. To demonstrate the variety, the selected studies highlight different aspects of these interactions. In the first chapter I will give a short introduction on the pain and the stress systems and their ways of interaction. Furthermore, I will give a short summary of the studies presented in Chapter II to V and their background. The results and their meaning for future research will be discussed in the last part of the first chapter. Chronic pain syndromes have been associated with chronic stress and alterations of the HPA axis resulting in chronic hypocortisolism. But if these alterations may play a causal role in the pathophysiology of chronic pain remains unclear. Thus, the study described in Chapter II investigated the effects of pharmacological induced hypocortisolism on pain perception. Both, the stress and the pain system are related to the cardiovascular system. Increase of blood pressure is part of the stress reaction and leads to reduced pain perception. Therefore, it is important for the usage of pain tests to keep in mind potential interferences from activation of the cardiovascular system, especially when pain inhibitory processes are investigated. For this reason we compared two commonly and interchangeably used pain tests with regard to the triggered autonomic reactions. This study is described in chapter III. Chapter IV and V deal with the role of learning processes in pain and related influences of stress. Processes of classical conditioning play an important role for symptom generation and manifestation. In both studies aversive eyeblink conditioning was used as a model for pain learning. In the study described in Chapter IV we compared classical eyeblink conditioning in healthy volunteers to patients suffering from fibromyalgia, a chronic pain disorder. Also, differences of the HPA axis, as part of the stress system, were taken in account. The study of Chapter V investigated effects of the very first stress reaction, particularly rapid non-genomic cortisol effects. Healthy volunteers received an intravenous cortisol administration immediately before the eyeblink conditioning. Rapid effects have only been demonstrated on a cellular level and on animal behavior so far. In general, the studies presented in this work may give an impression of the broad variety of possible interactions between the pain and the stress system. Furthermore, they contribute to our knowledge about theses interactions. However, more research is needed to complete the picture.
Stress is a common phenomenon for animals living in the wild, but also for humans in modern societies. Originally, the body's stress response is an adaptive reaction to a possibly life-threatening situation, and it has been shown to impact on energy distribution and metabolism, thereby increasing the chance of survival. However, stress has also been shown to impact on mating behaviour and reproductive strategies in animals and humans. This work deals with the effect of stress on reproductive behavior. Up to now, research has only focused on the effects of stress on reproduction in general. The effects of stress on reproduction may be looked at from two points of view. First, stress affects reproductive functioning by endocrine (e.g. glucocorticoid) actions on the reproductive system. However, stress can also influence reproductive behavior, i.e. mate choice and mating preferences. Animals and humans do not mate randomly, but exhibit preferences towards mating partners. One factor by which animals and humans choose their mating partners is similarity vs. dissimilarity: Similar mates usually carry more of one's own genes and the cooperation between similar mates is, at least theoretically, less hampered by expressing diverse behaviors. By mating with dissimilar mates on the other hand one may acquire new qualities for oneself, but also for one's offspring, useful to cope with environmental challenge. In humans we usually find a preference for similar mates. Due to the high costs of breeding, variables like cooperation and life-long partnerships may play a greater role than the acquaintance of new qualities.The present work focuses on stress effects on mating preferences of humans and will give a first answer to the question whether stress may affect our preference for similar mates. Stress and mating preferences are at the centre of this work. Thus, in the first Chapter I will give an introduction on stress and mating preferences and link these topics to each other. Furthermore, I will give a short summary of the studies described in Chapter II - Chapter IV and close the chapter with a general discussion of the findings and directions for further research on stress and mating preferences. Human mating behavior is complex, and many aspects of it may not relate to biology but social conventions and education. This work will not focus on those aspects but rather on cognitive and affective processing of erotic and sexually-relevant stimuli, since we assume that these aspects of mating behaviour are likely related to psychobiological stress mechanisms. Therefore, a paradigm is needed that measures such aspects of mating preferences in humans. The studies presented in Chapter II and Chapter III were performed in order to develop such a paradigm. In these studies we show that affective startle modulation may be used to indicate differences in sexual approach motivation to potential mating partners with different similarity levels to the participant. In Chapter IV, I will describe a study that aimed to investigate the effects of stress on human mating preferences. We showed that stress reverses human mating preferences: While unstressed individuals show a preference for similar mates, stressed individuals seem to prefer dissimilar mates. Overall, the studies presented in this work showed that affective startle modulation can be employed to measure mating preferences in humans and that these mating preferences are influenced by stress.
Aggression is one of the most researched topics in psychology. This is understandable, since aggression behavior does a lot of harm to individuals and groups. A lot is known already about the biology of aggression, but one system that seems to be of vital importance in animals has largely been overlooked: the hypothalamic-pituitary-adrenal (HPA) axis. Menno Kruk and Jószef Haller and their research teams developed rodent models of adaptive, normal, and abnormal aggressive behavior. They found the acute HPA axis (re)activity, but also chronic basal levels to be causally relevant in the elicitation and escalation of aggressive behavior. As a mediating variable, changes in the processing of relevant social information is proposed, although this could not be tested in animals. In humans, not a lot of research has been done, but there is evidence for both the association between acute and basal cortisol levels in (abnormal) aggression. However, not many of these studies have been experimental of nature. rnrnOur aim was to add to the understanding of both basal chronic levels of HPA axis activity, as well as acute levels in the formation of aggressive behavior. Therefore, we did two experiments, both with healthy student samples. In both studies we induced aggression with a well validated paradigm from social psychology: the Taylor Aggression Paradigm. Half of the subjects, however, only went through a non-provoking control condition. We measured trait basal levels of HPA axis activity on three days prior. We took several cortisol samples before, during, and after the task. After the induction of aggression, we measured the behavioral and electrophysiological brain response to relevant social stimuli, i.e., emotional facial expressions embedded in an emotional Stroop task. In the second study, we pharmacologically manipulated cortisol levels 60min before the beginning of the experiment. To do that, half of the subjects were administered 20mg of hydrocortisone, which elevates circulating cortisol levels (cortisol group), the other half was administered a placebo (placebo group). Results showed that acute HPA axis activity is indeed relevant for aggressive behavior. We found in Study 1 a difference in cortisol levels after the aggression induction in the provoked group compared to the non-provoked group (i.e., a heightened reactivity of the HPA axis). However, this could not be replicated in Study 2. Furthermore, the pharmacological elevation of cortisol levels led to an increase in aggressive behavior in women compared to the placebo group. There were no effects in men, so that while men were significantly more aggressive than women in the placebo group, they were equally aggressive in the cortisol group. Furthermore, there was an interaction of cortisol treatment with block of the Taylor Aggression Paradigm, in that the cortisol group was significantly more aggressive in the third block of the task. Concerning basal HPA axis activity, we found an effect on aggressive behavior in both studies, albeit more consistently in women and in the provoked and non-provoked groups. However, the effect was not apparent in the cortisol group. After the aggressive encounter, information processing patterns were changed in the provoked compared to the non-provoked group for all facial expressions, especially anger. These results indicate that the HPA axis plays an important role in the formation of aggressive behavior in humans, as well. Importantly, different changes within the system, be it basal or acute, are associated with the same outcome in this task. More studies are needed, however, to better understand the role that each plays in different kinds of aggressive behavior, and the role information processing plays as a possible mediating variable. This extensive knowledge is necessary for better behavioral interventions.
Im Fokus dieser Untersuchung steht die Evaluation allgemeinpsychiatrischer tagesklinischer Behandlung, einerseits zur Überprüfung der Wirksamkeit der teilstationären Intervention bzgl. der Symptomatik, andererseits unter der speziellen Berücksichtigung von generalisierten Vertrauensaspekten (Vertrauenstrias) auf dem theoretischen Hintergrund des Handlungstheoretischen Partialmodells der Persönlichkeit (Krampen, 1987) und ihren Zusammenhängen zu psychischen Erkrankungen. Dem wurde in einer Fragebogenstudie mit 200 tagesklinischen Patienten im Alter von 16 bis 80 Jahren, die im Zeitraum von Oktober 2002 bis Februar 2004 in einer südwestdeutschen Kleinstadt teilstationär aufgenommen worden waren, nachgegangen. Die Patienten unterscheiden sich sowohl in den soziodemographischen Variablen als auch in Diagnosen und Behandlungszeiträumen. Wie in den Hypothesen angenommen, kann in dieser Studie gezeigt werden, dass die teilstationäre Behandlung eine deutliche Verringerung der psychischen Belastung mit sich bringt und Vertrauen " mit Ausnahme von interpersonalem " gesteigert wird. Weiterhin wurden negative Zusammenhänge zwischen Vertrauen und psychischer Krankheit/Gesundheit und Unterschiede bezüglich einzelner Störungsbilder angenommen. Die einzelnen Hypothesen hierzu werden ebenfalls durch diese Studie größtenteils bestätigt.
In this thesis, three studies investigating the impact of stress on the protective startle eye blink reflex are reported. In the first study a decrease in prepulse inhibition of the startle reflex was observed after intravenous low dose cortisol application. In the second study a decrease in reflex magnitude of the startle reflex was observed after pharmacological suppression of endogenous cortisol production. In the third study, a higher reflex magnitude of the startle reflex was observed at reduced arterial and central venous blood pressure. These results can be interpreted in terms of an adaption to hostile environments.
Die folgende Arbeit thematisiert die Konzeptualisierung des psychischen Phänomens der Internalisierten Homonegativität (IH; Shidlo, 1994). Dieses bezeichnet die Verinnerlichung negativer Einstellungen und Verhaltensweisen gegenüber Homosexualität seitens einer gleichgeschlechtlich orientierten Person, wobei die Konstrukte von Heteronormativität und Homonegativität als Grundlage der Introjektion anzusehen sind. Bereits bestehende, in Art und Anzahl ihrer Dimensionen divergierende Begriffsbestimmungen werden zu einer neuen Arbeitsdefinition integriert. In diesem Sinne wird das Konstrukt der IH durch die Faktoren Internalisierter Homonegativität und Internalisierter Homopositivität mit je einer selbstbezogenen und globalen Subkomponente definiert. Ihre Antezedenzien und Konsequenzen, im Sinne psychischen Leidens oder stressbezogenen Selbstwachstums werden unter Einbezug ihrer Korrelate im Rahmen des Minoritätenstress-Modells (Meyer, 1995) reflektiert. Auch werden bereits existierende explizite und implizite diagnostische Messinstrumente zur Erfassung von IH bezüglich ihrer psychometrischen Qualität analysiert sowie konzeptuelle Ideen eines solchen für den deutschsprachigen Raum aufgezeigt.
WICHTIGER HINWEIS: Aufgrund eines Computerfehlers bei der Rohdatenaufbereitung, müssen die 5.2.3. Ergebnisse (S. 43 ff.) wie folgt korrigiert werden: Explizite Einstellungsmessung Die Ergebnisse ändern sich inhaltlich: Haupteffekt Wortvalenz F(1, 94) = 51.10, p < .001, η2 = .35, (Mpos= 5.06; Mneg= -28.51); Interaktionseffekt Wortvalenz und kognitive Belastung F(1, 94) = 7.90, p < .01, η2 = .08, (Mpos/load= -5.01; Mpos/kein load= 15.13; Mneg/load= -25.43; Mneg/kein load= -31.75); Haupteffekt Wortnegation F(1, 94) = 8.58, p < .01, η2 = .08, (Mkeine = -7.95; Mnegation= -15.58). Implizite Einstellungsmessung Die Ergebnisse bleiben inhaltlich gleich: Zweifach-Interaktion von Wortvalenz und Prime, F(1, 80) = 4.61, p < .05, η2 = .06, (Mpos/wahr= 20.33; Mpos/falsch= 3.85; Mneg/wahr= 4.44; Mneg/falsch = 14.14). ABSTRACT: Ziel der vorliegenden Arbeit war es Evidenz für die Existenz einer Antonymie-Heuristik bei der Falsifikation valenter Information zu finden. Es wird angenommen, dass die vorherige Ankündigung, dass eine nachfolgende valenzhafte Information falsch ist, zu einer Änderung der Enkodierungsstrategie der valenzhaften Information führt. Dies bedeutet, dass zu der Valenz der gegebenen Information automatisch eine Gegenvalenz oder antonyme Valenz aktiviert werden sollte. Dementsprechend sollten falsche positive Informationen negativer und falsche negative Informationen positiver beurteilt werden als ihre wahren Entsprechungen. In vier Studien konnte dieser Effekt nachgewiesen werden. Die Ankündigung, dass eine valenzhafte Information falsch ist, beeinflusst, unabhängig von kognitiver Belastung, die Valenzübertragung in einem evaluativen Konditionierungsparadigma in vorhergesagter Weise (Experiment1). Ebenso führen generierte Gegenvalenzen, wenn eine Information als falsch angekündigt wurde, zu einem Verarbeitungsvorteil in einer Valenzkategorisierungs-Aufgabe, bei welcher positive Informationen als negativ und negative Informationen als positiv eingeschätzt werden sollten (Experiment 2). Die Ankündigung, dass eine nachfolgende Information falsch ist, führt außerdem dazu, dass positive (negative) Eigenschaften schnell und effizient negativer (positiver) eingeschätzt werden als bei einer Ankündigung der Informationen als wahr (Experiment 3 und 4). Zusammenfassend werden diese Befunde als Evidenz für die Existenz einer Antonymie-Heuristik im Zuge der Falsifikation valenter Information interpretiert.
The overall objective of this thesis was to gain a deeper understanding of the antecedents, processes, and manifestations of uniqueness-driven consumer behavior. To achieve this goal, five studies have been conducted in Germany and Switzerland with a total of 1048 participants across different demographic and socio-economic backgrounds. Two concepts were employed in all studies: Consumer need for uniqueness (CNFU) and general uniqueness perception (GUP). CNFU (Tian, Bearden, & Hunter, 2001), a mainly US"based consumer research concept, measures the individual need, and thus the motivation to acquire, use, and dispose consumer goods in order to develop a unique image. GUP, adapted from the two-component theory of individuality (Kampmeier, 2001), represents a global and direct measure of self-ascribed uniqueness. Study #1 looked at the interrelation of the uniqueness-driven concepts. Therefore, GUP and CNFU were employed in the study as potential psychological factors that influence and predict uniqueness-driven consumer behavior. Different behavioral measures were used: The newly developed possession of individualized products (POIP), the newly developed products for uniqueness display (PFUD), and the already established uniqueness-enhancing behaviors (UEB). Analyses showed that CNFU mediates the relationship between GUP and the behavioral measures in a German speaking setting. Thus, GUP (representing self-perception) was identified as the driver behind CNFU (representing motivation) and the actual consumer behavior. Study #2 examined further manifestations of uniqueness-driven consumer behavior. For this purpose, an extreme form of uniqueness-increasing behavior was researched: Tattooing. The influence of GUP and CNFU on tattooing behavior was investigated using a sample derived from a tattoo exhibition. To do so, a newly developed measure to determine the percentage of the body covered by tattoos was employed. It was revealed that individuals with higher GUP and CNFU levels indeed have a higher tattooing degree. Study #3 further explored the predictive possibilities and limitations of the GUP and CNFU concepts. On the one hand, study #3 specifically looked at the consumption of customized apparel products as mass customization is said to become the standard of the century (Piller & Müller, 2004). It was shown that individuals with higher CNFU levels not only purchased more customized apparel products in the last six months, but also spend more money on them. On the other hand, uniqueness-enhancing activities (UEA), such as travel to exotic places or extreme sports, were investigated by using a newly developed 30-item scale. It was revealed that CNFU partly mediates the GUP and UEA relationship, proving that CNFU indeed predicts a broad range of consumer behaviors and that GUP is the driver behind the need and the behavior. Study #4, entered a new terrain. In contrast to the previous three studies, it explored the so termed "passive" side of uniqueness-seeking in the consumer context. Individuals might feel unique because business companies treat them in a special way. Such a unique customer treatment (UCT) involves activities like customer service or customer relationship management. Study #4 investigated if individuals differ in their need for such a treatment. Hence, with the need for unique customer treatment (NFUCT) a new uniqueness-driven consumer need was introduced and its impact on customer loyalty examined. Analyses, for example, revealed that individuals with high NFUCT levels receiving a high unique customer treatment (UCT) showed the highest customer loyalty, whereas the lowest customer loyalty was found among those individuals with high NFUCT levels receiving a low unique customer treatment (UCT). Study #5 mainly examined the processes behind uniqueness-driven consumer behavior. Here, not only the psychological influences, but also situational influences were examined. This study investigated the impact of a non-personal "indirect" uniqueness manipulation on the consumption of customized apparel products by simultaneously controlling for the influence of GUP and CNFU. Therefore, two equal experimental groups were created. Afterwards, these groups either received an e-mail with a "pro-individualism" campaign or a "pro-collectivism" campaign especially developed for study #5. The conducted experiment revealed that, individuals receiving a "pro-individualism" poster campaign telling the participants that uniqueness is socially appropriate and desired were willing to spend more money on customization options compared to individuals receiving a "pro-collectivism" poster campaign. Hence, not only psychological antecedents such as GUP and CNFU influence uniqueness-driven consumer behavior, but also situational factors.
Monatelange Wartezeiten auf einen ambulanten Psychotherapieplatz sind der Regelfall im deutschen Gesundheitssystem. Die Veränderung der Symptombelastung der Patienten in der Wartezeit ist bislang allerdings kaum empirisch untersucht worden. In der vorliegenden Arbeit wurden an einer Stichprobe ambulanter Psychotherapiepatienten die Ausprägungen und Veränderungen der allgemeinen psychischen Symptombelastung während der durchschnittlich sechsmonatigen Wartezeit auf den Psychotherapieplatz untersucht. Zudem wurde überprüft, mit welchen Merkmalen die Symptombelastungen zum Zeitpunkt der Anmeldung zur Therapie und zum Zeitpunkt des Erstgesprächs sowie ihre Veränderungen in der Wartezeit zusammenhängen. Die dabei untersuchten Persönlichkeitsmerkmale wurden aus theoretischen Rahmenmodellen abgeleitet. Hierzu gehören die aktionale Entwicklungspsychologie, das handlungstheoretische Partialmodell der Persönlichkeit mit der darin eingeordneten Vertrauens-Trias und das Androgynie-Modell der psychischen Gesundheit. Nach einem direkten Veränderungskriterium zeigten 48 % der Patienten in der Wartezeit keine bedeutsame Veränderung, 29 % eine Verbesserung und 23 % eine Verschlechterung. Durch die bei der Anmeldung erfassten Persönlichkeitsmerkmale konnten Verbesserungen, Verschlechterungen und gleichbleibende Symptombelastungen in der Wartezeit anhand einer multinomialen logistischen Regressionsanalyse für 60 % der Patienten korrekt vorausgesagt werden. Eine traditionelle normative Geschlechtsrollen-Orientierung stellt einen negativen Prädiktor für eine Verbesserung dar. Soziales Vertrauen konnte Verschlechterungen negativ vorhersagen. Bei Hoffnungslosigkeit handelt es sich um einen marginal negativen Prädiktor für eine Verbesserung. Ein hoch ausgeprägtes Selbstkonzept eigener Fähigkeiten ist ein positiver Prädiktor für eine Verschlechterung. Hinsichtlich der soziodemografischen und störungsbezogenen Merkmale konnten das Alter, das Geschlecht und die Anzahl der Diagnosen die Veränderungen der Symptombelastung in der Wartezeit zu 54 % korrekt vorhersagen. Das Alter ist ein positiver Prädiktor für eine Verschlechterung. Weibliches Geschlecht und die Anzahl an Diagnosen sind negative Prädiktoren für eine Verbesserung. Darüber hinaus wurden differenzierte Zusammenhänge zwischen den Persönlichkeitsmerkmalen und der Symptombelastung exploratorisch untersucht.
Stress represents a significant problem for Western societies inducing costs as high as 3-4 % of the European gross national products, a burden that is continually increasing (WHO Briefing, EUR/04/5047810/B6). The classical stress response system is the hypothalamic-pituitary-adrenal (HPA) axis which acts to restore homeostasis after disturbances. Two major components within the HPA axis system are the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). Cortisol, released from the adrenal glands at the end of the HPA axis, binds to MRs and with a 10 fold lower affinity to GRs. Both, impairment of the HPA axis and an imbalance in the MR/GR ratio enhances the risk for infection, inflammation and stress related psychiatric disorders. Major depressive disorder (MDD) is characterised by a variety of symptoms, however, one of the most consistent findings is the hyperactivity of the HPA axis. This may be the result of lower numbers or reduced activity of GRs and MRs. The GR gene consists of multiple alternative first exons resulting in different GR mRNA transcripts whereas for the MR only two first exons are known to date. Both, the human GR promoter 1F and the homologue rat Gr promoter 1.7 seem to be susceptible to methylation during stressful early life events resulting in lower 1F/1.7 transcript levels. It was proposed that this is due to methylation of a NGFI-A binding site in both, the rat promoter 1.7 and the human promoter 1F. The research presented in this thesis was undertaken to determine the differential expression and methylation patterns of GR and MR variants in multiple areas of the limbic brain system in the healthy and depressed human brain. Furthermore, the transcriptional control of the GR transcript 1F was investigated as expression changes of this transcript were associated with MDD, childhood abuse and early life stress. The role of NGFI-A and several other transcription factors on 1F regulation was studied in vitro and the effect of Ngfi-a overexpression on the rat Gr promoter 1.7 in vivo. The susceptibility to epigenetic programming of several GR promoters was investigated in MDD. In addition, changes in methylation levels have been determined in response to a single acute stressor in rodents. Our results showed that GR and MR first exon transcripts are differentially expressed in the human brain, but this is not due to epigenetic programming. We showed that NGFI-A has no effect on endogenous 1F/1.7 expression in vitro and in vivo. We provide evidence that the transcription factor E2F1 is a major element in the transcriptional complex necessary to drive the expression of GR 1F transcripts. In rats, highly individual methylation patterns in the paraventricular nucleus of the hypothalamus (PVN) suggest that this is not related to the stressor but can rather be interpreted as pre-existing differences. In contrast, the hippocampus showed a much more uniform epigenetic status, but still is susceptible to epigenetic modification even after a single acute stress suggesting a differential "state‟ versus "trait‟ regulation of the GR gene in different brain regions. The results of this thesis have given further insight in the complex transcriptional regulation of GR and MR first exons in health and disease. Epigenetic programming of GR promoters seems to be involved in early life stress and acute stress in adult rats; however, the susceptibility to methylation in response to stress seems to vary between brain regions.
The brain is the central coordinator of the human stress reaction. At the same time, peripheral endocrine and neural stress signals act on the brain modulating brain function. Here, three experimental studies are presented demonstrating this dual role of the brain in stress. Study I shows that centrally acting insulin, an important regulator of energy homeostasis, attenuates the stress related cortisol secretion. Studies II and III show that specific components of the stress reaction modulate learning and memory retrieval, two important aspects of higher-order brain function.
During pregnancy every eighth woman is treated with glucocorticoids. Glucocorticoids inhibit cell division but are assumed to accelerate the differentiation of cells. In this review animal models for the development of the human fetal and neonatal hypothalamic-pituitary-adrenal (HPA) axis are investigated. It is possible to show that during pregnancy in humans, as in most of the here-investigated animal models, a stress hyporesponsive period (SHRP) is present. In this period, the fetus is facing reduced glucocorticoid concentrations, by low or absent fetal glucocorticoid synthesis and by reduced exposure to maternal glucocorticoids. During that phase, sensitive maturational processes in the brain are assumed, which could be inhibited by high glucocorticoid concentrations. In the SHRP, species-specific maximal brain growth spurt and neurogenesis of the somatosensory cortex take place. The latter is critical for the development of social and communication skills and the secure attachment of mother and child. Glucocorticoid treatment during pregnancy needs to be further investigated especially during this vulnerable SHRP. The hypothalamus and the pituitary stimulate the adrenal glucocorticoid production. On the other hand, glucocorticoids can inhibit the synthesis of corticotropin-releasing hormone (CRH) in the hypothalamus and of adrenocorticotropic hormone (ACTH) in the pituitary. Alterations in this negative feedback are assumed among others in the development of fibromyalgia, diabetes and factors of the metabolic syndrome. In this work it is shown that the fetal cortisol surge at the end of gestation is at least partially due to reduced glucocorticoid negative feedback. It is also assumed that androgens are involved in the control of fetal glucocorticoid synthesis. Glucocorticoids seem to prevent masculinization of the female fetus by androgens during the sexual gonadal development. In this work a negative interaction of glucocorticoids and androgens is detectable.
Die Einführung leistungsorientierter Entgeltsysteme stellt Mitarbeiter und Unternehmen vor besondere Herausforderungen. Dabei verändert sich vor allem die Rolle des Mitarbeiters. War er vormals Ausführender der ihm übertragenen Arbeitsaufgaben, wird er zunehmend zum eigenverantwortlichen Gestalter und Mitunternehmer. Im Rahmen einer multiplen Fallstudie wird zunächst der Frage nachgegangen, wie die Mitarbeiter in drei karitativen Einrichtungen die Einführung einer leistungsorientierten Vergütungskomponente erleben. Dazu werden inhaltliche Gestaltungsmerkmale der Entgeltsysteme, Merkmale des Einführungsprozesses und ihre Auswirkungen untersucht. Die Ergebnisse zeigen, dass die Mitarbeiter in allen Einrichtungen dem Aspekt der Finanzierung des variablen Vergütungsanteils eine wesentliche Bedeutung beimessen. Wird dieser Anteil durch die Variabilisierung bisher garantierter, fixer Vergütungsanteile finanziert, entstehen unsichere Gehalts-anteile und es erhöht sich das Risiko von möglichen Gehaltsverlusten. In der Einrichtung mit dem höchsten Entgeltrisiko führte dieser Umstand dazu, dass Mitarbeiter und Vorgesetzte durch informelle Absprachen versucht haben, mögliche Verluste zu vermeiden. Wird der variable Entgeltanteil durch die Einrichtungen mitfinanziert, erhöhen sich hingegen die Chancen auf Einkommensgewinne, was auch zu einer höheren Akzeptanz der neuen Entgeltsysteme beiträgt. Aufbauend auf den Ergebnissen der Fallstudie werden in einer quantitativen Analyse die Auswirkungen eines erhöhten Entgeltrisikos auf die Zufriedenheit der Mitarbeiter mit ihrem variablen Vergütungsanteil (Bonuszufriedenheit) untersucht. Dabei wird das Entgeltrisiko durch drei konzeptuelle Facetten operationalisiert: die Variabilität der Entlohnung, das Ausmaß möglicher Verluste und das Verhältnis von Risiko und Chance (RCV). Entgegen der bisherigen Annahme in der Forschungsliteratur, dass vor allem die Variabilität der Entlohnung ausschlaggebend für die Auswirkungen von Entgeltrisiko ist, zeigen regressionsanalytische Ergebnisse, dass in der Einführungsphase neuer Entgeltsysteme vor allem das RCV einen signifikanten Effekt auf die Bonuszufriedenheit der Mitarbeiter hat. Die Ergebnisse einer multiplen Mediationsanalyse legen nahe, dass der Effekt von RCV auf die Bonuszufriedenheit zum Teil von Einstellungen der distributiven und prozeduralen Gerechtigkeit vermittelt wird. Wei-terführende Analysen ergeben, dass der Zusammenhang zwischen dem RCV und der Bonuszufriedenheit durch zwei moderierende Variablen beeinflusst wird: zum einen durch die partizipative Beteiligung der Mitarbeiter am Einführungsprozess und zum anderen durch die individuelle Präferenz für leistungsorientierte Entlohnung. Vor allem bei hoher partizipativer Beteiligung wirkt sich ein günstiges RCV positiv auf die Bonuszufriedenheit der Mitarbeiter aus. Außerdem sind jene Mitarbeiter unzufriedener mit einem risiko-reichen Entgeltsystem, die eine stark ausgeprägte Präferenz für leistungsorientierte Entlohnung besitzen.
Cortisol is a stress hormone that acts on the central nervous system in order to support adaptation and time-adjusted coping processes. Whereas previous research has focused on slow emerging, genomic effects of cortisol likely mediated by protein synthesis, there is only limited knowledge about rapid, non-genomic cortisol effects on in vivo neuronal cell activity in humans. Three independent placebo-controlled studies in healthy men were conducted to test effects of 4 mg cortisol on central nervous system activity, occurring within 15 minutes after intravenous administration. Two of the studies (N = 26; N = 9) used continuous arterial spin labeling as a magnetic resonance imaging sequence, and found rapid bilateral thalamic perfusion decrements. The third study (N = 14) revealed rapid cortisol-induced changes in global signal strength and map complexity of the electroencephalogram. The observed changes in neuronal functioning suggest that cortisol may act on the thalamic relay of non-relevant background as well as on task specific sensory information in order to facilitate the adaptation to stress challenges. In conclusion, these results are the first to coherently suggest that a physiologically plausible amount of cortisol profoundly affects functioning and perfusion of the human CNS in vivo by a rapid, non-genomic mechanism.
By rodent studies it has been shown that the mineralocorticoid receptor (MR) is a candidate gene for the investigation of cognitive functions comparable to human executive function. The present work addresses the question if polymorphisms in the MR gene can act as a "probe" to explain a part of the interindividual variance of human executive functions. For this purpose, 72 healthy young participants were assigned to four equally sized groups, concerning their particular MR genotype for two common MR polymorphisms. They were investigated in an electroencephalogram (EEG) test session, accomplishing two cognitive tests while delivering saliva samples for subsequent cortisol measures. The two tests chosen for the assessment of executive functions were the Attention Network Task (ANT) and a modified version of the Wisconsin Card Sorting Test (WCST).Chapter 1 of the present work reports of the rational bases for the empirical approach, which were built up on a broad theoretical background presented in Chapter 2. In the third chapter, the investigation and results of the statistical analysis for behavioral data (i.e. reaction times, accuracy/error rates) are presented. No association with MR polymorphisms was found for the reaction times of both tests. For the accuracy rate, differences between genotype groups were found for ANT and WCST, indicating an association of MR polymorphisms and accuracy in the Alertness and Executive Control network of the ANT and during the detection of an intradimensional shift in the WCST. Data acquisition and the results for EEG data analyses are presented in Chapter 4. The results show that groups differing for MR genotype show different activity over prefrontal motor areas during the process of answering to the ANT. Those group differences again were prominent for the Alertness and Executive Control network. A tendency for further significant group differences was found for activity on frontopolar positions in extradimensional rule switching. Chapter 5 summarizes the findings for the analysis of salivary free cortisol, showing a tendency for an association between MR polymorphisms and a mildly stimulated Hypothalamus-pituitary-adrenal (HPA) axis during the test situation. The results of the different measures are integrated and discussed in Chapter 6 within the scope of novel findings in investigating the functionality of the chosen MR polymorphisms. Finally, Chapter 7 gives an outlook on the methodology and constraints of future research strategies to further describe the role of the MR in human cognitive function.
On the Influence of Ignored Stimuli: Generalization and Application of Distractor-Response Binding.
(2011)
In selection tasks where target stimuli are accompanied by distractors, responses to target stimuli, target stimuli and the distractor stimuli can be encoded together as one episode in memory. Subsequent repetition of any aspect of such an episode can lead to the retrieval of the whole episode including the response. Thus, repeating a distractor can retrieve responses given to previous targets; this mechanism was labeled distractor-response binding and has been evidenced in several visual setups. Three experiments of the present thesis implemented a priming paradigm with an identification task to generalize this mechanism to auditory and tactile stimuli as well as to stimulus concepts. In four more experiments the possible effect of distractor-response binding on drivers' reactions was investigated. The same paradigm was implemented using more complex stimuli, foot responses, go/no-go responses, and a dual task setup with head-up and head-down displays. The results indicate that distractor-response binding effects occur with auditory and tactile stimuli and that the process is mediated by a conceptual representation of the distractor stimuli. Distractor-response binding effects also revealed for stimuli, responses, and framework conditions likely to occur in a driving situation. It can be concluded that the effect of distractor-response binding needs to be taken into account for the design of local danger warnings in driver assistance systems.
In addition to the well-recognised effects of both, genes and adult environment, it is now broadly accepted that adverse conditions during pregnancy contribute to the development of mental and somatic disorders in the offspring, such as cardiovascular disorders, endocrinological disorders, metabolic disorders, schizophrenia, anxious and depressive behaviour and attention deficit hyperactivity disorder (ADHD). Early life events may have long lasting impact on tissue structure and function and these effects appear to underlie the developmental origins of vulnerability to chronic diseases. The assumption that prenatal adversity, such as maternal emotional states during pregnancy, may have adverse effects on the developing infant is not new. Accordant references can be found in an ancient Indian text (ca. 1050 before Christ), in biblical texts and in documents originating during the Middle Ages. Even Hippocrates stated possible effects of maternal emotional states on the developing fetus. Since the mid-1950s, research examining the effects of maternal psychosocial stress during pregnancy appeared in the literature. Extensive research in this field has been conducted since the early 1990s. Thus, the relationship between early life events and long-term health outcomes was already postulated over 20 years ago. David Barker and colleagues demonstrated that children of lower birth weight - which represents a crude marker of an adverse intrauterine environment - were at increased risk of high blood pressure, cardiovascular disorders, and type-2 diabetes later in life. These provocative findings led to a large amount of subsequent research, initially focussing on the role of undernutrition in determining fetal outcomes. The phenomenon of prenatal influences that determine in part the risk of suffering from chronic disease later in life has been named the "fetal origins of health and disease" paradigm. The concept of "prenatal programming" has now been extended to many other domains, such as the effects of prenatal maternal stress, prenatal tobacco exposure, alcohol intake, medication, toxins, as well as maternal infection and diseases. During the process of prenatal programming, environmental agents are transmitted across the placenta and act on specific fetal tissues during sensitive periods of development. Thus, developmental trajectories are changed and the organisation and function of tissue structure and organ system is altered. The biological purpose of those "early life programming" may consist in evolutionary advantages. The offspring adapts its development to the expected extrauterine environment which is forecast by the clues available during fetal life. If the fetus receives signals of a challenging environment, e.g. due to maternal stress hormones or maternal undernutrition, its survival may be promoted due to developmental adaptation processes. However, if the expected environment does not match with the real environment, maladapation and later disease risk may result. For example, a possible indicator of a "response ready" trait, such as hyperactivity/inattention may have been advantageous in an adverse ancient environment. However, it is of disadvantage when the postnatal environment demands oppositional skills, such as attention and concentration " e.g. in the classroom, at school, to achieve academic success. Borderline personality disorder (BPD) is a prevalent psychiatric disorder, characterized by impulsivity, affective instability, dysfunctional interpersonal relationships and identity disturbance. Although many studies report different risk factors, the exact etiologic mechanisms are not yet understood. In addition to the well-recognised effects of genetic components and adverse childhood experiences, BPD may potentially be co-determined by further environmental influences, acting very early in life: during pre- and perinatal period. There are several hints that may suggest possible prenatal programming processes in BPD. For example, patients with BPD are characterized by elevated stress sensitivity and reactivity and dysfunctions of the neuroendocrine stress system, such as the hypothalamic pituitary adrenal (HPA) axis. Furthermore, patients with BPD show a broad range of somatic comorbidities " especially those disorders for which prenatal programming processes have been described. During infancy and childhood, BPD patients already show behavioural and emotional abnormalities as well as pronounced temperamental traits, such as impulsivity, emotional dysregulation and inattention that may potentially be co-determined by prenatal programming processes. Such temperamental traits - similar to those, seen in patients with ADHD - have been described to be associated with low birthweight which indicates a suboptimal intrauterine environment. Moreover, the functional and structural alterations in the central nervous system (CNS) in patients with BPD might also be mediated in part by prenatal agents, such as prenatal tobacco exposure. Prenatal adversity may thus constitute a further, additional component in the multifactorial genesis of BPD. The association between BPD and prenatal risk factors has not yet been studied in such detail. We are not aware of any further study that assessed pre- and perinatal risk factors, such as maternal psychoscocial stress, smoking, alcohol intake, obstetric complications and lack of breastfeeding in patients with BPD.
The role of cortisol and cortisol dynamics in patients after aneurysmal subarachnoid hemorrhage
(2011)
Spontaneous aneurysmal subarachnoid hemorrhage (SAH) is a form of stroke which constitutes a severe trauma to the brain and often leads to serious long-term medical and psychosocial sequels which persist for years after the acute event. Recently, adrenocorticotrophic hormone deficiency has been identified as one possible consequence of the bleeding and is assumed to occur in around 20% of all survivors. Additionally, a number of studies report a high prevalence of post-SAH symptoms such as lack of initiative, fatigue, loss of concentration, impaired quality of life and psychiatric symptoms such as depression. The overlap of these symptoms and those of patients with untreated partial or complete hypopituitarism lead to the suggestion that neuroendocrine dysregulations may contribute to the psychosocial sequels of SAH. Therefore, one of the aims of this work is to gain insights into the role of neuroendocrine dysfunction on quality of life and the prevalence of psychiatric sequels in SAH-patients. Additionally, as data on cortisol dynamics after SAH are scarce, diurnal cortisol profiles are investigated in patients in the acute and chronic phase, as well as the cortisol awakening response and feedback sensitivity in the chronic phase after SAH. As a result, it can be shown that some SAH patients exhibit lower serum cortisol levels but at the same time a higher cortisol awakening response in saliva than healthy controls. Also, patients in the chronic phase after SAH do have a stable diurnal cortisol rhythm while there are disturbances in around 50% of all patients in the acute phase, leading to the conclusion that a single baseline measurement of cortisol is of no substantial use for diagnosing cortisol dysregulations in the acute phase after SAH. It is assumed that in SAH patients endocrine changes occur over time and that a combination of adrenal exhaustion and a subsequent downregulation of corticosteroid binding globulin may be the most probable causes for the dissociation of serum cortisol concentrations and salivary cortisol profiles in the investigated SAH patients. These changes may be an emergency response after SAH and, as elevated free cortisol levels are connected to a better psychosocial outcome in patients in the chronic phase after SAH, this reaction may even be adaptive.
Die Vertrauens-Trias erlaubt salutogentische Aussagen über personale Ressourcen. Die kulturvergleichende Anwendung der Vertrauens-Trias wurde bei Jugendlichen in drei Ländern (Deutschland, Luxemburg, Spanien) überprüft. Dabei wurde die Konstruktvalidität der Vertrauens-Trias als auch Zusammenhänge zu symptomatischen Belastungen insgesamt bestätigt. Vergleiche zwischen den Kulturen zeigen keine Unterschiede zwischen deutschen und luxemburgischen Schülern, jedoch zwischen deutschen und spanischen Schülern.