Im Rahmen der vorliegenden Arbeit wurden anhand eines Tiermodells zunächst Hinweise für die pathogene Relevanz von Serumfaktoren für die Entstehung von chronischen Schmerzsyndromen und assoziierten Symptomen gesucht. Es zeigten sich bei Versuchsmäusen nach intraperitonealer Injektion von Serum eines Patienten mit komplexem regionalem Schmerzsyndrom (CRPS) im Vergleich zu Kontrolltieren, denen Serum von gesunden Blutspendern injiziert wurde, Veränderungen des Spezies-spezifischen, explorativen Verhaltensmusters, welche erste Hinweise auf schmerzassoziiertes Verhalten liefern. Aufgrund dieser Befunde und der Hypothese der Präsenz einer humoralen Autoimmunreaktion bei der Entstehung chronischer Schmerzsyndrome wurde die Seroprävalenz für Antikörper gegen eine Vielzahl potentieller Autoantigene bei Patienten mit CRPS oder Fibromyalgiesyndrom im Vergleich zu gesunden Kontrollprobanden mittels immunhistochemischer Färbungen gegen murines Gewebe untersucht, wobei kein für die beschriebenen Schmerzerkrankungen pathognomonischer Autoantikörper identifiziert werden konnte. Die vorliegende Arbeit erfüllte ihren Zweck als Pilotprojekt, indem sie wichtige Daten lieferte, die für weitere Untersuchungen wegweisend sind. Dies bezieht sich im Besondern auf notwendige Änderungen bei den In-vitro-Methoden zur Detektion von Autoantikörpern. Zudem müssen die In-vivo-Experimente unter Einbeziehung sensorischer Verhaltenstests wiederholt und durch Fraktionierung der injizierten Serumproben erweitert werden, um gegebenenfalls Autoantikörper als Pathogene der Erkrankungen identifizieren zu können. Die in der vorliegenden Arbeit beschriebenen Erkenntnisse bieten einen Einblick in mögliche pathophysiologische Mechanismen bei der Entstehung von chronischen, idiopathischen Schmerzzuständen und könnten als Basis für neue Überlegungen über den Einsatz immunmodulierender Therapiestrategien bei derartigen Syndromen dienen. / The first aim of this thesis was to give evidence for the pathogenic role of humoral blood serum factors for the development of chronic pain states and associated symptoms by means of an in-vivo passive-transfer model. Mice were injected intraperitoneally with serum of a patient suffering from complex regional pain syndrome (CRPS) whereas abnormalities of species-specific explorative behavioural patterns, indicative of pain-related behaviour, were noted compared to control mice which had been injected with serum from healthy blood donors. Following these findings and according to the subsequently established hypothesis of the presence of a humoral autoimmune pathogenesis in chronic pain disorders, the prevalence of serum antibodies against a broad spectrum of potential autoantigens was investigated in patients suffering from CRPS or fibromyalgia syndrome compared to healthy controls using immunohistochemical staining of murine tissue sections whereas no pathognomonic binding pattern specific for the above mentioned diseases was found. The findings given in this thesis can be considered as a pilot project as they provide important data seminal for further investigations, especially considering necessary methodological changes to detect serum autoantibodies. The in-vivo experiments also have to be repeated including specific sensory testing and the fractionation of the injected serum samples in order to identify autoantibodies as the relevant pathogenic components. The above mentioned findings provide insight to potential pathophysiological mechanisms in the development of chronic idiopathic pain states and may serve as a basis for considering immunomodulating therapeutic strategies in such disorders.

In einer systematischen Übersichtsarbeit mit Metaanalyse wurde chronischer Wundschmerz nach Sectio caesarea mit einer Inzidenz von jeweils 15,4%, 11,5% und 11,2% der Frauen nach 3 bis < 6, 6 bis < 12 und über 12 Monaten geschätzt. Chronische postoperative Schmerzen nach Kaiserschnitten sind somit ein relevantes klinisches Problem. Im zweiten Teil dieser Dissertation wurde in einer prospektiven Beobachtungsstudie die Inzidenz chronischer postoperativer Schmerzen nach 12 Monaten mit jeweils 12,1% nach Sectio caesarea, 13,7% nach Hysterektomie und 38,1% nach mammachirurgischen Eingriffen ermittelt. Als Risikofaktoren konnten die Komorbidität, der zeitliche Anteil akuter postoperativer starker Schmerzen sowie die Schmerzstärke der akuten postoperativen Schmerzen signifikant erkannt werden. / In this systematic review using meta-analysis the incidence of CPSP (= chronic postsurgical pain) was estimated at 15,4%, 11,5% and 11,2% at 3 to < 6, 6 to < 12 and > 12 months after CS (cesarean section), respectively. This is a clinically relevant issue. Secondly, in a prospective observational study the incidence of CPSP was described at 12,1% after CS, 13,7% after hysterectomy and 38,1% after mamma surgery. The predictive factors were comorbidity, the percentage of time in severe pain during the first 24 hours after surgery and the severity of postoperative pain.

Techn. Universiẗat, Diss., 2005--München.

Diplomarbeit Hochschule für Angewandte Psychologie Zürich, 2005.

No description available.

The 21st century world is characterized by globalization, optimization, high performance demands, and continuous acceleration of processes. Not surprisingly, stress has steadily become more prevalent over the past years and has become a permanent challenge for many of us. Still we are always expected to perform at our best, and an impairment of cognitive performance can be devastating, particularly in the professional world. This ubiquity in daily life of chronic stress, cognitive demands, and their potential interactions was the motivation for this dissertation. Among cognitive processes executive functioning (EF) are of particular interest, as they represent set of fundamental cognitive abilities for mastering daily life. More precisely, EF is described as higher-order cognitive processes that control and coordinate complex cognitive tasks (Diamond, 2013; Miyake et al., 2000). The primary aim of this dissertation was to investigate the interplay between chronic stress and EF in detail. A three-year longitudinal cohort, the StressCog cohort, was established for this purpose. In order to understand the longitudinal interplay between chronic stress and EF, methodological foundations and cross-sectional matters had to be investigated first. As a result, this dissertation encompasses the following three studies: With classical laboratory designs, the estimation of generalizable and robust effects on the relationship between chronic stress and EF is impaired. Therefore, the StressCog study was set up to make use of internet-based data assessment within domestic environments. Study 1 addressed the feasibility of internet-based response time data, including the common concern that internet-based response time data collected in domestic environments is subject to increased data variability (Chetverikov & Upravitelev, 2016; Reips, 2002). To this end, performance measures collected in the laboratory were compared with measures collected in domestic environments. We found that a setting-related difference in the variability of conventional performance measures (i.e., response times and error rates), as well as diffusion model-based measures is only of small size. An overall increase of variance of approximately 5% was visible in domestic environments. However, as internet-based assessments allow for the recruitment of larger sample sizes (Reips, 2002) the loss of static power can be easily compensated. Therefore, the findings of Study 1 support the use of internet-based cognitive data collection in domestic environments. This formed a valuable basis regarding the collection and interpretation of the StressCog data used in Study 2 and Study 3. In order to get a broad picture of chronic stress the StressCog study aimed for multimethod assessment. The subjective (i.e., perceived) extent of chronic stress and conceptually related constructs were assessed by multiple self-reported measures. The objective (i.e., physiological) extent of chronic stress was assessed via hair cortisol concentration, which has been established as a widely accepted biological marker of chronic stress (E. Russell et al., 2012; Stalder & Kirschbaum, 2012). Surprisingly, however, multiple studies have shown that hair cortisol concentration is, at best, only weakly correlated with subjective chronic stress (Stalder et al., 2017; Staufenbiel et al., 2013; Weckesser et al., 2019). This lack of psychoendocrine covariance was addressed in Study 2 by investigating the construct validity of commonly used chronic stress instruments. A multidimensional item response theory approach was applied in order to display the overlap between items of commonly used measures of chronic stress, depressiveness, and neuroticism. A common latent scale covered the major amount of variance (40% to 48%). It appeared that the overlap of content is mainly based on fatigue, which is a core symptom of depressiveness. Similar to previously reported findings, the common latent scale displayed only a weak association with hair cortisol concentration. It can therefore be argued that items of self-reported chronic stress do not reflect the physiological (i.e., endocrine) aspect of chronic stress to a satisfactory extent. Thus, the results of Study 2 were a valuable basis for the interpretation of chronic stress data in Study 3. In Study 3, we investigated the cross-sectional association between chronic stress and EF. The study made use of data from the baseline assessment of the StressCog cohort (N = 514). Using structural equation modelling, we found no evidence for a meaningful association between chronic stress (i.e., self-reported measures and hair cortisol concentration) and a common latent EF factor. The results found in Study 3 were further supported by unpublished longitudinal StressCog data and analyses making use of diffusion model performance measures. Considering the mainstream of existing findings, which suggests chronic stress to be negatively associated with EF (e.g., Deligkaris et al., 2014; Sandi, 2013), an absence of an association between chronic stress and EF seems surprising. However, other existing findings support this perspective (Castaneda et al., 2011a; McLennan et al., 2016). Beyond this, the results of Study 1 and 2 help to explain why a lack of an association between chronic stress and EF is quite plausible. As within traditional, laboratory-based settings a recruitment of larger samples sizes is difficult and costly, most existing studies lack large, representative samples. In consequence, many findings are based on narrow sample characteristics. Supported by the findings of Study 1, the StressCog study made use of internet-based data collection, which led to the establishment of one the largest, population-based cohorts in the field. Thus, the results presented in this dissertation can be seen as much more robust and representative than many other studies that suggest opposing results. The findings of Study 2 allow for the assumption that many studies in the field make use of questionable self-report instruments and that subjective (i.e., self-reported) measures of chronic stress are only weakly related to objective (i.e., HCC) measures. In consequence, results always depend on the operationalization of the chronic stress measures being used. Caution is advised when comparing opposing results of different measures. With regard to our daily life demands, it may appear quite promising that no association between chronic stress and EF was found in this dissertation. However, these results should not be misunderstood. It has been demonstrated countless times that chronic stress can severely affect the human organism, causing various negative effects that go far beyond a possible impairment of cognitive abilities. Knowing that chronic stress can impair EF under certain circumstances leads to the central question of what conditions make stress toxic. In order to answer this question further systematic research is needed, in which representative samples and experimental study designs will be of crucial help. As long as these questions are not satisfactorily clarified, it seems best to deal with the challenges of chronic stress in a conscious and responsible manner.

Einleitung 2004 wurde die multimodale Tagesklinik zur Therapie chronischer Schmerzen am UniversitätsSchmerzCentrum der Universitätsklinik Dresden eröffnet. Sie zeichnet sich bis heute durch die intensive Zusammenarbeit verschiedener Fachdisziplinen aus. Zur Qualitätssicherung wurde damals ein Konzept für eine formative Evaluation erarbeitet, das zum Einen aus Fragebögen der Deutschen Schmerzgesellschaft, aber auch aus selbst formulierten Items besteht. Dieses Konzept wurde bis heute verwendet und lieferte für verschiedene Fragestellungen bereits Daten. Ziel dieser Arbeit war zum einen, für einen Zeitraum von zwei Jahren die Wirksamkeit der multimodalen Tagesklinik auf verschiedene Parameter zu untersuchen. Zum anderen sollten die Möglichkeiten und Grenzen des formativen Evaluationskonzeptes betrachtet werden. Methodik Es wurden alle Patienten in die Untersuchung eingeschlossen, die zwischen Januar 2006 und Dezember 2008 an dem multimodalen Programm der Tagesklinik teilnahmen. Die Patienten werden in der Regel diesem Programm zugewiesen, wenn sie bereits längere Zeit über wiederkehrende bzw. persistierende Schmerzen klagen, die sie erheblich in ihrer Lebensführung einschränken. Darüber hinaus sollten sie eine psychische Diagnose haben, die für eine seelische Beeinträchtigung steht. Sie müssen körperlich ausreichend belastbar sein, um das physiotherapeutische Programm zu tolerieren sowie sollten ausreichend für diese Therapie motiviert sein. Von 352 Patienten aus diesem Zeitraum liegen für 214 (60,8%) komplett ausgefüllte Fragebögen vor (von T1 bis T6 bzw. von T0 bis T6). Das Durchschnittsalter der vorliegenden Stichprobe ist 49,5 Jahre (SD 10,37), 73,0% sind Frauen. Der größte Anteil der Patienten weist ein Chronifizierungsstadium III auf (45,5%), ist angestellt (50%), voll erwerbstätig (29,8%), hat Rückenschmerzen (44,3%) und bezieht seine finanziellen Mittel aus der Arbeitstätigkeit (41,5%) Für die Bestimmung der Wirksamkeit wurden verschiedene Variablen auf ihre Mittelwertveränderungen im Verlauf untersucht. Zum Einsatz kamen Fragebögen zur Erfassung der Schmerzstärke (NRS), der schmerzbedingten Beeinträchtigung (PDI), der gesundheitsbezogenen Lebensqualität (SF 36), der Schmerzwahrnehmung (SES), des Copings (CSQ), der Depressivität und Angst (HADS). Ergänzend wurden weitere Items erhoben, die sich auf soziodemographische, schmerzassoziierte Bereiche konzentrierten bzw. Items zur Therapiezufriedenheit. Die Auswertungen erfolgten anhand der SPSS Versionen 16.0-18.0 mit einfaktorieller Varianzanalyse bzw. Varianzanalyse mit Messwiederholung bei Sicherstellung der Voraussetzungen. Bei nicht normalverteilten Variablen wurden nonparametrische Verfahren eingesetzt. Die klinische Bedeutsamkeit wurde anhand von Effektstärken (adaptiert an das jeweilige Verfahren) bestimmt. Zur Bewertung des Konzeptes auf seine Güte als formative Evaluation wurden die Standards der Deutschen Gesellschaft für Evaluation (DeGEval, 2008) sowie die Checklisten von König (2000) herangezogen. Ergebnisse Aufgrund der Besonderheiten der Stichprobe musste zu Beginn der statistischen Auswertung eine Strukturierung des Datensatzes erfolgen, die mit Hilfe von einer Faktorenanalyse und dann folgend einer Clusteranalyse vorgenommen wurde. Es ergaben sich 6 Cluster, die inhaltlich für diese Auswertung sinnvoll zu unterscheiden waren. Diese Clusterung wurde für alle Prozesse beibehalten. Hinsichtlich der Durchschnittlichen und der größten Schmerzstärke sowie der Katastrophisierung (CSQ) wurden sehr gute Therapieergebnisse erreicht; ausreichend gut wurden auch die Ergebnisse der schmerzbedingten Beeinträchtigung (PDI), der körperlichen Lebensqualität (SF 36 KSK), der affektiven Schmerzbewertung (SES affektiv) und der Variable Beten und Hoffen (CSQ) dokumentiert (mindestens mittlere Effektstärken). Dabei unterscheiden sich auch die Cluster hinsichtlich ihrer Response. Am besten konnten Cluster 2 und Cluster 5 profitieren, die mindestens 7 Variablen (von 19 ausgewerteten) große bzw. mittlere Effekte aufwiesen. Im Verlauf der Untersuchung zeigten sich erhebliche methodische Limitierungen, angefangen von konzeptionellen Missverständnissen beim CSQ, über mangelnde statistische Absicherung von Variablen aufgrund heterogener Stichprobenmerkmale zu diesen Variablen, bis hin zu unauswertbaren Variablen aufgrund von ungenügender Itemkonstruktion. Für einige Variablen ist deren Gültigkeit in dieser Stichprobe als Therapieerfolgskriterium fragwürdig (z.Bsp. HADS D), weil die meisten der hier untersuchten Patienten unauffällig ausgeprägt sind. Die fehlenden Kriterien zur Beurteilung von Therapieerfolg in der multimodalen Therapie chronischer Schmerzen erschweren eine transparente Bewertung der Ergebnisse im Hinblick auf Therapieerfolg und Wirksamkeit. Die methodischen Limitierungen werden eingehend diskutiert. Für das Konzept der Evaluation als formatives Vorgehen wurden ebenfalls anhand der Standards der DeGEval (2008) und König (2000) Limitierungen gefunden, die die Güte einschränken. Vor allem die Zieldefinition und damit einhergehend die Operationalisierung sind nicht ausreichend erfolgt. Die Fragestellungen wurden aus der Literatur in unterschiedlich brauchbarer Form extrahiert und konnten daher auch nur bedingt beantwortet werden. Ein großer Teil der Fragestellungen war zu wenig konkret, um messbare Variablen daraus abzuleiten. Das führt zum zweiten Problem des Konzeptes, das anhand sehr vieler Items umsetzt ist. Allerdings ist die Überlappung zwischen Fragestellung und Items eher gering: ein großer Teil der Items konnte in diesem Rahmen nicht ausgewertet werden, weil die Fragestellung dazu fehlte, ein Teil der Fragestellungen wiederum war nicht durch Items bzw. Variablen abgedeckt. Die aufgegriffenen Items bzw. Variablen letztendlich waren zum Teil von geringer Güte, Gültigkeit bzw. ausreichender statistischer Güte, so dass für den Umfang der Erhebung der Ertrag eher dürftig ausfällt. Darüber hinaus war die Abbildung der multimodalen Therapie einseitig psychologisch. Es sind wenige ärztliche Fragen auszuwerten gewesen; für physiotherapeutische Fragestellungen, die grob identifiziert wurden, fanden sich keine wesentlichen Abbildungen in den erhobenen Fragen. Weder für ärztliche Fragestellungen noch für physiotherapeutische konnten Ergebnisse erstellt werden. Schlussfolgerungen Die Wirksamkeit der multimodalen Tagesklinik am UniversitätsSchmerzCentrum zeigt sich unterschiedlich hinsichtlich der Variablen bzw. der untersuchten Cluster: unterschiedliche Cluster reagierten unterschiedlich in ihrer Veränderung über den Verlauf. Auch die Cluster selbst zeichneten sich durch unterschiedliche Profile aus. Für diesen Bereich der Ergebnisse sind weitere Analysen zu Patienten, die mit Verbesserungen ihrer Werte auf die Therapie reagieren (Respondern), wünschenswert, um die inhaltliche Passung von Patient und Therapie zu optimieren. Insgesamt stellt sich die Frage, ob Kriterien, die im Rahmen eines Qualitätsmanagements eher globalere Konstrukte wie Lebensqualität erheben, für die Erfordernisse einer formativen Evaluation ausreichend sind. Im hier vorliegenden Fall ist das Ergebnis nicht eindeutig auf die inhaltliche Arbeit zu beziehen und kann daher nicht helfen, den Therapieprozess zu adaptieren. Physiotherapeutische und ärztliche Fragestellungen sind wenig vertreten und in dieser Untersuchung schlecht valide gewesen. Die Konstruktion eines Fragebogens zur formativen Evaluation sollte in jedem Falle anhand von Testgütekriterien stattfinden, um sich Frustrationen zu ersparen. Des Weiteren sollte das Vorgehen auch an die oben skizzierten Probleme angepasst werden. Das bedeutet jedoch erhebliche methodische und konzeptionelle Arbeit.

No description available.

Background: Chronic pain is a major public health problem. The impact of stages of chronic pain adjusted for disease load on societal burden has not been assessed in population surveys. Methods: A cross-sectional survey with 4360 people aged ≥ 14 years representative of the German population was conducted. Measures obtained included demographic variables, presence of chronic pain (based on the definition of the International Association for the Study of Pain), chronic pain stages (by chronic pain grade questionnaire), disease load (by self-reported comorbidity questionnaire) and societal burden (by self-reported number of doctor visits, nights spent in hospital and days of sick leave/disability in the previous 12 months, and by current unemployment). Associations between chronic pain stages with societal burden, adjusted for demographic variables and disease load, were tested by Poisson and logistic regression analyses. Results: 2508 responses were received. 19.4% (95% CI 16.8% to 22.0%) of participants met the criteria of chronic non-disabling non-malignant pain. 7.4% (95% CI 5.0% to 9.9%) met criteria for chronic disabling non-malignant pain. Compared with no chronic pain, the rate ratio (RR) of days with sick leave/disability was 1.6 for non-disabling pain and 6.4 for disabling pain. After adjusting for age and disease load, the RRs increased to 1.8 and 6.8. The RR of doctor visits was 2.5 for non-disabling pain and 4.5 for disabling pain if compared with no chronic pain. After adjusting for age and disease load, the RR fell to 1.7 and 2.6. The RR of days in hospital was 2.7 for non-disabling pain and 11.7 for disabling pain if compared with no chronic pain. After adjusting for age and disease load, the RR fell to 1.5 and 4.0. Unemployment was predicted by lower educational level (Odds Ratio OR 3.27 [95% CI 1.70-6.29]), disabling pain (OR 3.30 [95% CI 1.76-6.21]) and disease load (OR 1.70 [95% CI 1.41-2.05]). Conclusion: Chronic pain stages, but also disease load and societal inequalities contributed to societal burden. Pain measurements in epidemiology research of chronic pain should include chronic pain grades and disease load.

Summary: Salivary alpha-amylase: More than an enzyme - Investigating confounders of stress-induced and basal amylase activity (Dipl.-Psych. Jana Strahler) The hypothalamus-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS) are two of the major systems playing a role in the adaptation of organisms to developmental changes that threaten homeostasis. The HPA system involves the secretion of glucocorticoids, including cortisol, into the circulatory system. Numerous studies have been published that introduced salivary cortisol to assess HPA axis activity and therefore strengthens its role as an easy obtainable biomarker in stress research that can be monitored easily and frequently. Recent findings suggest a possible surrogate marker of autonomic activity due to autonomic innervation of salivary glands: salivary alpha-amylase (sAA). Up to date, additional methodological research is needed for a better understanding of the advantages and disadvantages of sAA activity in comparison to already established markers of ANS activity. The aim of the present thesis is to further our knowledge of confounders of sAA activity under basal and acute stress conditions and to strengthen the validity of this enzyme as an easy obtainable alternative for ANS testing. After introducing classical and modern stress concepts and stress system physiology (chapter 2), the reader is acquainted with anatomical basics of salivary gland innervation and secretion of salivary proteins, including sAA, due to autonomic innervation (chapter 3 and 4). Afterwards, a more nuanced review of methodological considerations of sAA determination shows gaps of knowledge concerning its usefulness as a marker of ANS activity (chapter 5). Given the fact that the integration of sAA into developmental and aging research is a relative recent phenomenon, several issues have to be addressed before a final conclusion could be drawn. Therefore, we conducted a series of studies incorporating these considerations regarding behavioral correlates of inter- and intraindividual differences in sAA activity with a special emphasis on older adults. Chapter 7 deals with sAA activity under psychological stress conditions in different age groups. Since vulnerability to disease and disease prevalence patterns change with age, it is important to investigate stress reactivity of people in different age groups. We therefore investigated children between 6 and 10 years, because childhood is a sensitive period of growth and development, and thus plays an important role for later life health. Young adults were included to represent the most studied human age group as a reference. Older adults between 59 and 61 years were investigated, because at this age the course is set for the further development of a person’s health in later life, and because autonomic stress responses in older age might be important determinants of cardiovascular and inflammatory aging. Our goal is to test for associations of sAA with more established stress system markers, i.e., salivary cortisol as outcome measurement of HPA reactivity, heart rate (HR) and heart rate variability (HRV) as markers for autonomic reactivity, and to directly compare these responses between different age groups across the life span. Secretion of sAA and cortisol was repeatedly assessed in 62 children, 78 young adults, and 74 older adults after exposure to a standardized psychosocial stressor, the Trier Social Stress Test. In addition, cardiovascular activity was measured in both adult groups. Older adults showed attenuated sAA, HR, and HRV responses. Furthermore, we found higher sAA but lower cortisol at baseline as well as lower sAA and cortisol responses in children. Age by sex interactions were observed only for cortisol with higher responses in older male participants. No associations between the parameters were found. Results in children and young adults confirm previous results. Overall, findings implicate sAA as an alternative or additional autonomic stress marker throughout the life span, with marked and rapid responsiveness to stress in three relevant age groups. The impact of age and chronic stress on basal sAA activity is the center of interest in chapter 8. We therefore assessed diurnal profiles of sAA and salivary cortisol in 27 younger and 31 older competitive ballroom dancers as well as 26 younger and 33 older age- and sex-matched controls. According to the Allostatic Load concept, repeated, non-habituating responses to social-evaluative conditions, which characterize the lives of competitive ballroom dancers, should be associated with stress system dysregulations. Furthermore, we expect to see an increased sympathetic drive associated higher overall alpha-amylase activity in older adults. Analyses revealed an elevated daily overall output of sAA in older adults while there was no effect of age on mean cortisol levels. Alterations of diurnal rhythms were only seen in younger male dancers showing a flattened diurnal profile of sAA and younger dancers and female older dancers showing a blunted diurnal rhythmicity of cortisol. Furthermore, we found a negative correlation between summary indices of basal sAA and the amount of physical activity. In conclusion, higher overall output of sAA in older adults was in line with the phenomenon of a “sympathetic overdrive” with increasing age. Furthermore, a lower output of sAA in people who are more physical active was in line with the hypothesis of an exercise-induced decrease of sympathetic activity. Taken together, results of chapter 7 and 8 show a clear impact of age on sAA activity, either under acute stress or basal conditions. One problem when integrating sAA into developmental and aging research is the use of adrenergic agonists and antagonists what is very common in older adults, i.e. antihypertensive drugs (AD). As well, the previously shown sympathetic overactivity that occurs with normal aging is associated with higher blood pressure (BP). Therefore, chapter 9 deals with a possible impact of high BP and AD on diurnal sAA activity in 79 older adults (33 normotensive adults, 16 medicated vs. 45 hypertensive adults, 34 medicated). Results showed a pronounced rhythm of sAA in all groups. Diurnal profiles differed significantly between men and women with men lacking the typical decrease of sAA in the morning and showing more pronounced alterations throughout the day. An effect of AD on sAA profiles and area under the curve values indicates that subjects not using AD´s show a heightened diurnal profile and a higher total output of sAA. Descriptively, this was also true for hypertensive older adults. Hypertensive subjects and those not using AD showed the highest diurnal output of sAA and the steepest slope. In sum, our results show an impact of antihypertensive medication and a difference between normotensive and hypertensive subjects on characteristics of diurnal sAA activity. Hence, findings are of particular interest in research using sAA as a prognostic indicator of pathological states and processes. Given the fact that hypertension was also shown to be associated with substantial changes of transmitters within the suprachiasmatic nucleus (SCN) - the “biological clock” that receives photic input from retinal glands via the retinohypothalamic pathway - and an altered output from the SCN to the sympathetic nervous system, we broaden the idea of a possible effect of different lighting conditions on morning sAA profiles in chapter 10. In a counterbalanced within-subjects design six men and 16 women of different ages collected sAA morning profiles on two consecutive days with leaving their shutters closed on the one day (= dark) and open their shutters on the other day (= bright). We were able to replicate earlier findings of light-induced changes of salivary cortisol with higher responses during the bright condition. On either day, women showed larger cortisol increases than men. Despite multisynaptic autonomic connections arising from the SCN projecting to multiple organs of the body, we could not find an effect of sunlight on sAA morning profiles. Evidence for circadian clock gene expression in human oral mucosa might account for this result and indicates that peripheral oscillators may act more like integrators of multiple different time cues, e.g. light, food intake, instead of a “master” oscillator (SCN). Results of chapter 7 to 10 provide clear evidence that sAA is heightened in states of autonomic arousal, i.e. stress, aging and hypertension, and that its circadian rhythmicity seems to be regulated rather integrative than directly via efferent input from hypothalamic SCN neurons. In chapter 11 this thesis tries to approach one central question: What is the biological meaning of the findings made? According to this enzyme´s anti-bacterial and digestive action short term changes might not have a biological meaning itself but rather reflect just a small part of multiple coordinated body responses to stressful stimuli. While the sympathetic branch of the ANS mainly stimulates protein secretion, the parasympathetic branch stimulates saliva flow. Acute stress responses might therefore be interpreted as reflecting predominant sympathetic activity together with parasympathetic withdrawal. The same mechanism could also be suitable for the finding of higher diurnal levels of sAA in older adults or hypertensive subjects reflecting a higher peripheral sympathetic tone in these groups. Diurnal profiles of sAA itself may reflect circadian changes in autonomic balance. Circadian rhythms are of great advantage since they enable individuals to anticipate. This pre-adaptation enables the individual to cope with upcoming demands and challenges. Our finding of a relationship between sAA and salivary cortisol what strengthens the relevance of glucocorticoids that were previously shown to be able to phase shift circadian rhythms in cells and tissue. Within a food-related context there is evidence that decreasing levels of sAA in the morning could reflect increases of feeling hungry since sAA systematically increases during food consumption and with the subjective state of satiety. So far, much more research is needed to identify underlying physiological mechanisms of circadian sAA rhythmicity. Taking the next step, future studies will have to focus on the integration of sAA assessment into longitudinal studies and different disease states to prove its applicability as a marker of sympathetic neural functioning in the genesis and prognosis of disease.