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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.
Numerous RCTs demonstrate that cognitive behavioral therapy (CBT) for depression is effective. However, these findings are not necessarily representative of CBT under routine care conditions. Routine care studies are not usually subjected to comparable standardizations, e.g. often therapists may not follow treatment manuals and patients are less homogeneous with regard to their diagnoses and sociodemographic variables. Results on the transferability of findings from clinical trials to routine care are sparse and point in different directions. As RCT samples are selective due to a stringent application of inclusion/exclusion criteria, comparisons between routine care and clinical trials must be based on a consistent analytic strategy. The present work demonstrates the merits of propensity score matching (PSM), which offers solutions to reduce bias by balancing two samples based on a range of pretreatment differences. The objective of this dissertation is the investigation of the transferability of findings from RCTs to routine care settings.
Background: We evaluated depression and social isolation assessed at time of waitlisting as predictors of survival in heart transplant (HTx) recipients. Methods and Results: Between 2005 and 2006, 318 adult HTx candidates were enrolled in the Waiting for a New Heart Study, and 164 received transplantation. Patients were followed until February 2013. Psychosocial characteristics were assessed by questionnaires. Eurotransplant provided medical data at waitlisting, transplantation dates, and donor characteristics; hospitals reported medical data at HTx and date of death after HTx. During a median followâ€up of 70 months (<1"93 months postâ€HTx), 56 (38%) of 148 transplanted patients with complete data died. Depression scores were unrelated to social isolation, and neither correlated with disease severity. Higher depression scores increased the risk of dying (hazard ratio=1.07, 95% confidence interval, 1.01, 1.15, P=0.032), which was moderated by social isolation scores (significant interaction term; hazard ratio = 0.985, 95% confidence interval, 0.973, 0.998; P=0.022). These findings were maintained in multivariate models controlling for covariates (P values 0.020"0.039). Actuarial 1â€year/5â€year survival was best for patients with low depression who were not socially isolated at waitlisting (86% after 1 year, 79% after 5 years). Survival of those who were either depressed, or socially isolated or both, was lower, especially 5 years posttransplant (56%, 60%, and 62%, respectively). Conclusions: Low depression in conjunction with social integration at time of waitlisting is related to enhanced chances for survival after HTx. Both factors should be considered for inclusion in standardized assessments and interventions for HTx candidates. We evaluated depression and social isolation assessed at time of waitlisting as predictors of survival in heart transplant (HTx) recipients.\r\n\r\nMethods and Results: Between 2005 and 2006, 318 adult HTx candidates were enrolled in the Waiting for a New Heart Study, and 164 received transplantation. Patients were followed until February 2013. Psychosocial characteristics were assessed by questionnaires. Eurotransplant provided medical data at waitlisting, transplantation dates, and donor characteristics; hospitals reported medical data at HTx and date of death after HTx. During a median followâ€up of 70 months (<1"93 months postâ€HTx), 56 (38%) of 148 transplanted patients with complete data died. Depression scores were unrelated to social isolation, and neither correlated with disease severity. Higher depression scores increased the risk of dying (hazard ratio=1.07, 95% confidence interval, 1.01, 1.15, P=0.032), which was moderated by social isolation scores (significant interaction term; hazard ratio = 0.985, 95% confidence interval, 0.973, 0.998; P=0.022). These findings were maintained in multivariate models controlling for covariates (P values 0.020"0.039). Actuarial 1â€year/5â€year survival was best for patients with low depression who were not socially isolated at waitlisting (86% after 1 year, 79% after 5 years). Survival of those who were either depressed, or socially isolated or both, was lower, especially 5 years posttransplant (56%, 60%, and 62%, respectively).
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.