Mineralocorticoid receptor (MR)-mediated signaling in the brain has been suggested as a protective factor in the development of psychopathology, in particular mood disorders. We recently identified... Show moreMineralocorticoid receptor (MR)-mediated signaling in the brain has been suggested as a protective factor in the development of psychopathology, in particular mood disorders. We recently identified genomic loci at which either MR or the closely related glucocorticoid receptor (GR) binds selectively, and found members of the NeuroD transcription factor family to be specifically associated with MR-bound DNA in the rat hippocampus. We show here using forebrain-specific MR knockout mice that GR binding to MR/GR joint target loci is not affected in any major way in the absence of MR. Neurod2 binding was also independent of MR binding. Moreover, functional comparison with MyoD family members indicates that it is the chromatin remodeling aspect of NeuroD, rather than its direct stimulation of transcription, that is responsible for potentiation of MR-mediated transcription. These findings suggest that NeuroD acts in a permissive way to enhance MR-mediated transcription, and they argue against competition for DNA binding as a mechanism of MR- over GR-specific binding. Show less
Plessis, M.R. du; Smeekens, S.; Cillessen, A.H.N.; Whittle, S.; Güroğlu, B. 2019
Self-esteem moderates the relationship between stress and (cardiovascular) health, with low self-esteem potentially exacerbating the impact of stressors. Boosting self-esteem may therefore help to... Show moreSelf-esteem moderates the relationship between stress and (cardiovascular) health, with low self-esteem potentially exacerbating the impact of stressors. Boosting self-esteem may therefore help to buffer against stress. Subliminal evaluative conditioning (SEC), which subliminally couples self-words with positive words, has previously been successfully used to boost self-esteem, but the existing studies are in need of replication. In this article, we aimed to replicate and extend previous SEC studies. The first 2 experiments simultaneously examined whether SEC increased self-esteem (Experiment 1, n=84) and reduced cardiovascular reactivity to a stressor in high worriers (Experiment 2, n=77). On the basis of these results, the 3rd experiment was set up to examine whether an adjusted personalized SEC task increased self-esteem and reduced cardiac activity in high worriers (n=81). Across the 3 experiments, no effects were found of SEC on implicit or explicit self-esteem or affect or on cardiovascular (re)activity compared to a control condition in which the self was coupled with neutral words. The results do not support the use of the subliminal intervention in its current format. As stress is highly prevalent, future studies should focus on developing other cost-effective and evidence-based interventions. Show less
Previous studies reveal an elevated suicide rate for anaesthesiologists. We sought to examine anaesthesiologist suicide mortality and its underlying explanatory factors. Two studies were conducted... Show morePrevious studies reveal an elevated suicide rate for anaesthesiologists. We sought to examine anaesthesiologist suicide mortality and its underlying explanatory factors. Two studies were conducted in order to establish the suicide mortality figures among Dutch anaesthesiologists and to investigate life events, workrelated stress, psychological problems and alcohol- and drug abuse in relation to suicidal ideation. The results suggest that suicide mortality in anaesthesiologists in The Netherlands is elevated, and comparable to that in other Western countries, but small numbers prevent robust testing of this difference. Anaesthesiologists are more likely than the general population to experience sleeping problems and suicidal ideation; male anaesthesiologists are more likely to suffer from depression. The prevalence of suicide among this population may be related to a high prevalence of psychological problems, in addition to the knowledge and availability of means. Areas of suicide prevention among this group are discussed. Show less
Kloet, E.R. de; Claessens, S.E.F.; Kentrop, J. 2014
Prematurely born infants may be at risk, because of inadequate maturation of tissues. If there are signs of preterm birth, it has become common practice therefore to treat either antenatally the... Show morePrematurely born infants may be at risk, because of inadequate maturation of tissues. If there are signs of preterm birth, it has become common practice therefore to treat either antenatally the mother or postnatally the infant with glucocorticoids to accelerate tissue development, particularly of the lung. However, this life-saving early glucocorticoid treatment was found to increase the risk of adverse outcome in later life. In one animal study, the authors reported a 25% shorter lifespan of rats treated as newborns with the synthetic glucocorticoid dexamethasone, but so far this finding has not been replicated. After a brief clinical introduction, we discuss studies in rodents designed to examine how perinatal glucocorticoid action affects the developing brain. It appears that the perinatal action of the glucocorticoid depends on the context and the timing as well as the type of administered steroid. The type of steroid is important because the endogenous glucocorticoids cortisol and corticosterone bind to two distinct receptor populations, i.e., mineralocorticoid and glucocorticoid receptors (GR), while synthetic glucocorticoids predominantly bind to the GR. In addition, if given antenatally hydrocortisone is inactivated in the placenta by 11 beta-HSD type 2, and dexamethasone is not. With respect to timing, the outcome of glucocorticoid effects is different in early vs. late phases of brain development. The context refers to the environmental input that can affect the susceptibility to glucocorticoid action in the newborn rodent brain; early handling of pups and maternal care obliterate effects of post-natal dexamethasone treatment. Context also refers to coping with environmental conditions in later life, for which the individual may have been programed epigenetically by early-life experience. This knowledge of determinants affecting the outcome of perinatal glucocorticoid exposure may have clinical implications for the treatment of prematurely born infants. Show less
Werff, S.J.A. van der; Pannekoek, J.N.; Stein, D.J.; Wee, N.J.A. van der 2013
