BACKGROUND: Reported findings are inconsistent whether hypothalamic-pituitary-adrenal (HPA) signaling becomes hyperactive with increasing age, resulting in increasing levels of cortisol. Our... Show moreBACKGROUND: Reported findings are inconsistent whether hypothalamic-pituitary-adrenal (HPA) signaling becomes hyperactive with increasing age, resulting in increasing levels of cortisol. Our previous research strongly suggests that offspring from long-lived families are biologically younger. In this study we assessed whether these offspring have a lower HPA axis activity, as measured by lower levels of cortisol and higher cortisol feedback sensitivity. METHODS: Salivary cortisol levels were measured at four time points within the first hour upon awakening and at two time points in the evening in a cohort comprising 149 offspring and 154 partners from the Leiden Longevity Study. A dexamethasone suppression test was performed as a measure of cortisol feedback sensitivity. Age, gender and body mass index, smoking and disease history (type 2 diabetes and hypertension) were considered as possible confounding factors. RESULTS: Salivary cortisol secretion was lower in offspring compared to partners in the morning (Area Under the Curve = 15.6 versus 17.1 nmol/L, respectively; p = 0.048) and in the evening (Area Under the Curve = 3.32 versus 3.82 nmol/L, respectively; p = 0.024). Salivary cortisol levels were not different after dexamethasone (0.5 mg) suppression between offspring and partners (4.82 versus 5.26 nmol/L, respectively; p = 0.28). CONCLUSION: Offspring of nonagenarian siblings are marked by a lower HPA axis activity (reflected by lower diurnal salivary cortisol levels), but not by a difference in cortisol feedback sensitivity. Further in-depth studies aimed at characterizing the HPA axis in offspring and partners are needed. Show less
Whereas we know a fair amount on the role of the amygdala in the acute stress response, virtually nothing is known about its role during the recovery period after the stress has waned. Functional... Show moreWhereas we know a fair amount on the role of the amygdala in the acute stress response, virtually nothing is known about its role during the recovery period after the stress has waned. Functional connectivity analysis of the amygdala during this period might be useful in revealing brain circuits promoting adaptive recovery from a stressful event, as well as consolidation of emotionally relevant information in preparing for future challenges. Healthy participants were randomly assigned to either a psychosocial stress task (n = 18; stress group) or a comparable non-stressful control procedure (n = 20; controls). To study the prolonged effects of stress on amygdala functional connectivity, resting-state fMRI scans were acquired an hour after the stress task. Amygdala functional connectivity with other brain regions was assessed using seed-based correlations. The stress group exhibited a strong physiological and behavioral reaction to psychosocial stress exposure. Compared with controls the stress group showed increased amygdala functional connectivity with three cortical midline structures: the posterior cingulate cortex and precuneus (p<.05, corrected), and the medial prefrontal cortex (p<.05, small volume corrected). An hour after psychosocial stress, changes in amygdala functional connectivity were detected with cortical midline structures involved in the processing and regulation of emotions, as well as autobiographical memory. It is hypothesized that these effects could relate to top-down control of the amygdala and consolidation of self-relevant information after a stressful event. These results on functional connectivity in the recovery phase after stress might provide an important new vantage point in studying both sensitivity and resilience to stress. (C) 2011 Elsevier Inc. All rights reserved. Show less
Ferrarini, L.; Veer, I.M.; Lew, B. van; Oei, N.Y.L.; Buchem, M.A. van; Reiber, J.H.C.; ... ; Milles, J. 2011
In recent years, graph theory has been successfully applied to study functional and anatomical connectivity networks in the human brain. Most of these networks have shown small-world topological... Show moreIn recent years, graph theory has been successfully applied to study functional and anatomical connectivity networks in the human brain. Most of these networks have shown small-world topological characteristics: high efficiency in long distance communication between nodes, combined with highly interconnected local clusters of nodes. Moreover. functional studies performed at high resolutions have presented convincing evidence that resting-state functional connectivity networks exhibits (exponentially truncated) scale-free behavior. Such evidence, however. was mostly presented qualitatively, in terms of linear regressions of the degree distributions on log-log plots. Even when quantitative measures were given, these were usually limited to the r(2) correlation coefficient. However, the r2 statistic is not an optimal estimator of explained variance, when dealing with (truncated) power-law models. Recent developments in statistics have introduced new non-parametric approaches. based on the Kolmogorov-Smirnov test, for the problem of model selection. In this work, we have built on this idea to statistically tackle the issue of model selection for the degree distribution of functional connectivity at rest. The analysis, performed at voxel level and in a subject-specific fashion, confirmed the superiority of a truncated power-law model, showing high consistency across subjects. Moreover, the most highly connected voxels were found to be consistently part of the default mode network. Our results provide statistically sound support to the evidence previously presented in literature for a truncated power-law model of resting-state functional connectivity. (C) 2011 Elsevier Inc. All rights reserved. Show less
The present thesis contains five experimental studies into the effects of stress on memory I healthy males. Hydrocortisone (and propranolol) administration or the induction of social stress are... Show moreThe present thesis contains five experimental studies into the effects of stress on memory I healthy males. Hydrocortisone (and propranolol) administration or the induction of social stress are used to heighten cortisol levels, and consequently to study its effects on working memory performance and memory retrieval. In addition, by using neutral and emotional distraction during working memory, effects of cortisol on emotional distraction were investigated, also with use of functional imaging. Overall, it was consistently found that high cortisol levels, by hydrocortisone administration or induced by stress, reduced the distraction by emotional irrelevant stimuli, hence improving working memory. The current findings might be relevant for patients suffering from posttraumatic stress disorder, who typically suffer from trauma-related intrusions. Show less
Oei, N.Y.L.; Tollenaar, M.S.; Elzinga, B.M.; Spinhoven, P. 2010
Noradrenalin modulates prefrontal function, such as working memory (WM), and is associated with enhanced distractibility, and enhanced memory for emotional events and stimuli. The beta-blocker... Show moreNoradrenalin modulates prefrontal function, such as working memory (WM), and is associated with enhanced distractibility, and enhanced memory for emotional events and stimuli. The beta-blocker propranolol has been shown to reduce memory for emotional stimuli. Herein we describe investigations aimed at assessing whether the administration of propranolol would reduce the interference by emotional distractions during WM performance. In a between-subjects design, 48 young, healthy men received 80 mg propranolol (n = 25) or placebo (n = 23), before performing an "emotional Sternberg task" with neutral and negatively arousing distracters. Compared to placebo, propranolol impaired WM at low load, however, it also reduced the interference by emotional distracters at high load. Furthermore, an explorative moderated-mediation analysis indicated that the observed propranolol effects on emotional distraction were partially mediated by cortisol. In future non-clinical and clinical memory studies using propranolol administration, cortisol elevations should be monitored to further investigate the potential mediating role of cortisol. (c) 2009 Elsevier Inc. All rights reserved. Show less
