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Fibromyalgia is a disorder of unknown etiology characterized by widespread, chronic musculoskeletal pain of at least three month duration and pressure hyperalgesia at specific tender points on clinical examination. The disorder is accompanied by a multitude of additional symptoms such as fatigue, sleep disturbances, morning stiffness, depression, and anxiety. In terms of biological disturbances, low cortisol concentrations have been repeatedly observed in blood and urine samples of fibromyalgia patients, both under basal and stress-induced conditions. The aim of this dissertation was to investigate the presence of low cortisol concentrations (hypocortisolism) and potential accompanying alterations on sympathetic and immunological levels in female fibromyalgia patients. Beside the expected hypocortisolism, a higher norepinephrine secretion and lower natural killer cell levels were found in the patient group compared to a control group consisting of healthy, age-matched women. In addition, an increased activity of some pro-inflammatory markers was observed thus leading to alterations in the balance of pro-/anti-inflammatory activity. The results underline the relevance of simultaneous investigations of interacting bodily systems for a better understanding of underlying biological mechanisms in stress-related disorders.
Objective: Only 20-25% of the variance for the two to four-fold increased risk of developing breast cancer among women with family histories of the disease can be explained by known gene mutations. Other factors must exist. Here, a familial breast cancer model is proposed in which overestimation of risk, general distress, and cancer-specific distress constitute the type of background stress sufficient to increase unrelated acute stress reactivity in women at familial risk for breast cancer. Furthermore, these stress reactions are thought to be associated with central adiposity, an independent well-established risk factor for breast cancer. Hence, stress through its hormonal correlates and possible associations with central adiposity may play a crucial role in the etiology of breast cancer in women at familial risk for the disease. Methods: Participants were 215 healthy working women with first-degree relatives diagnosed before (high familial risk) or after age 50 (low familial risk), or without breast cancer in first-degree relatives (no familial risk). Participants completed self-report measures of perceived lifetime breast cancer risk, intrusive thoughts and avoidance about breast cancer (Impact of Event Scale), negative affect (Profile of Mood States), and general distress (Brief Symptom Inventory). Anthropometric measurements were taken. Urine samples during work, home, and sleep were collected for assessment of cortisol responses in the naturalistic setting where work was conceptualized as the stressful time of the day. Results: A series of analyses indicated a gradient increase of cortisol levels in response to the work environment from no, low, to high familial risk of breast cancer. When adding breast cancer intrusions to the model with familial risk status predicting work cortisol levels, significant intrusion effects emerged rendering the familial risk group non-significant. However, due to a lack of association between intrusions and cortisol in the low and high familial risk group separately, as well as a significant difference between low and high familial risk on intrusions, but not on work cortisol levels, full mediation of familial risk group effects on work cortisol by intrusions could not be established. A separate analysis indicated increased levels of central but not general adiposity in women at high familial risk of breast cancer compared to the low and no risk groups. There were no significant associations between central adiposity and cortisol excretion. Conclusion: A hyperactive hypothalamus-pituitary-adrenal axis with a more pronounced excretion of its end product cortisol, as well as elevated levels of central but not overall adiposity in women at high familial risk for breast cancer may indicate an increased health risk which expands beyond that of increased breast cancer risk for these women.
Software and interactive systems that adapt their behavior to the user are often referred to as Adaptive Systems. These systems infer the user's goals, knowledge or preferences by observing the user's actions. A synposis of 43 published studies demonstrated that only few of the existing systems are evaluated empirically. Most studies failed to show an advantage of the user model. A new framework is proposed that categorizes existing studies and defines an evaluation procedure which is able to uncover failures and maladaptations in the user model. It consists of four layers: evaluation of input data, evaluation of inference, evaluation of adaptation decision and evaluation of total interaction. Exemplary, the framework has been applied to the HTML-Tutor, an online-course that adapts to the learners' knowledge. Several empirical studies are described that test the accuracy of the user models, and explore the effects of adaptation to knowledge respectively prior knowledge. Generalization issues of the approach are discussed.
There is considerable evidence for an association between chronic dysregulation of the hypothalamus-pituitary adrenal (HPA) axis, atrophy of the hippocampus (HC) and cognitive and mood changes in clinical populations and in aging. The present thesis investigated this relationship in young healthy male subjects. Special emphasis was put on measures of HC volume and function derived from structural and functional magnetic resonance imaging (MRI). Higher cortisol levels after awakening were observed in subjects with higher levels of depressive symptomatology. Larger HC volume was associated with higher cortisol levels after awakening and in response to acute stress, whereas cognitive performance was impaired in subjects with larger HC volumes. Hippocampal activation during picture encoding was reduced after stress induction, and positive associations between activation and cognitive performance before stress were not present anymore afterwards. The present findings underscore the importance of structural and functional brain imaging for psychoneuroendocrinological research. The investigation of the association between cortisol levels and hippocampal integrity in young healthy subjects elicited unexpected results and adds to the understanding of HPA dysfunction and HC atrophy in clinical and aged populations.