Purpose: People with intellectual disabilities often show challenging behaviour, which can manifest itself in self-harm or aggression towards others. Real-time monitoring of stress in clients with... Show morePurpose: People with intellectual disabilities often show challenging behaviour, which can manifest itself in self-harm or aggression towards others. Real-time monitoring of stress in clients with challenging behaviour can help caregivers to promptly deploy interventions to prevent escalations, ultimately to improve the quality of life of client and caregiver. This study aimed to assess the impact of real-time stress monitoring with HUME, and the subsequent interventions deployed by the care team, on stress levels and quality of life. Materials and methods: Real-time stress monitoring was used in 41 clients with intellectual disabilities in a long-term care setting over a period of six months. Stress levels were determined at the start and during the deployment of the stress monitoring system. The quality of life of the client and caregiver was measured with the Outcome Rating Scale at the start and at three months of use. Results: The results showed that the HUME-based interventions resulted in a stress reduction. The perceived quality of life was higher after three months for both the clients and caregivers. Furthermore, interventions to provide proximity were found to be most effective in reducing stress and increasing the client's quality of life. Conclusions: The study demonstrates that real-time stress monitoring with the HUME and the following interventions were effective. There was less stress in clients with an intellectual disability and an increase in the perceived quality of life. Future larger and randomized controlled studies are needed to confirm these findings. Show less
Meyer, M.; Meijer, O.; Hunt, H.; Belanoff, J.; Lima, A.; Kloet, E.R. de; ... ; Nicola, A.F. de 2023
Glucocorticoids exert antiinflammatory, antiproliferative and immunosupressive effects. Paradoxically they may also enhance inflammation particularly in the nervous system, as shown in Cushing &... Show moreGlucocorticoids exert antiinflammatory, antiproliferative and immunosupressive effects. Paradoxically they may also enhance inflammation particularly in the nervous system, as shown in Cushing & PRIME; syndrome and neurodegenerative disorders of humans and models of human diseases. ."The Wobbler mouse model of amyotrophic lateral sclerosis shows hypercorticoidism and neuroinflammation which subsided by treatment with the glucocorticoid receptor (GR) modulator Dazucorilant (CORT113176). This effect suggests that GR mediates the chronic glucocorticoid unwanted effects. We now tested this hypothesis using a chronic stress model resembling the condition of the Wobbler mouse Male NFR/NFR mice remained as controls or were subjected to a restraining / rotation stress protocol for 3 weeks, with a group of stressed mice receiving CORT113176 also for 3 weeks. We determined the mRNAS or reactive protein for the proinflamatory factors HMGB1, TLR4, NFkB, TNF & alpha;, markers of astrogliosis (GFAP, SOX9 and acquaporin 4), of microgliosis (Iba, CD11b, P2RY12 purinergic receptor) as well as serum IL1 & beta; and corticosterone. We showed that chronic stress produced high levels of serum corticosterone and IL1 & beta;, decreased body and spleen weight, produced microgliosis and astrogliosis and increased proinflammatory mediators. In stressed mice, modulation of the GR with CORT113176 reduced Iba + microgliosis, CD11b and P2RY12 mRNAs, immunoreactive HMGB1 + cells, GFAP + astrogliosis, SOX9 and acquaporin expression and TLR4 and NFkB mRNAs vs. stress-only mice. The effects of CORT113176 indicate that glucocorticoids are probably involved in neuroinflammation. Thus, modulation of the GR would become useful to dampen the inflammatory component of neurodegenerative disorders. Show less
The two-hit stress model predicts that exposure to stress at two different time-points in life may increase or decrease the risk of developing stress-related disorders later in life. Most studies... Show moreThe two-hit stress model predicts that exposure to stress at two different time-points in life may increase or decrease the risk of developing stress-related disorders later in life. Most studies based on the two-hit stress model have investigated early postnatal stress as the first hit with adult stress as the second hit. Adolescence, however, represents another highly sensitive developmental window during which exposure to stressful events may affect programming outcomes following exposure to stress in adulthood. Here, we discuss the programming effects of different types of stressors (social and nonsocial) occurring during adolescence (first hit) and how such stressors affect the responsiveness toward an additional stressor occurring during adulthood (second hit) in rodents. We then provide a comprehensive overview of the potential mechanisms underlying interindividual and sex differences in the resilience/susceptibility to developing stress-related disorders later in life when stress is experienced in two different life stages. Show less
Smart wearables are increasingly used to help people deal with stress. Still, a less explored area of research in this field concerns the partnerships that smart wearables can take on when engaging... Show moreSmart wearables are increasingly used to help people deal with stress. Still, a less explored area of research in this field concerns the partnerships that smart wearables can take on when engaging people in stress-coping activities. To facilitate further understanding of the human-wearable partnerships, we designed Grippy, a smart wearable system composed of a physical glove and a smartphone application to help the wearer actively explore and cope with stress in daily situations. We introduced Grippy, as a speculative probe, to six participants (four master students and two university employees) who wore it for five successive days. Participants were interviewed about their use experience of Grippy during and after these five days. Qualitative data collected from the interviews was interpreted regarding how Grippy could fit into people’s stress-coping activities across different daily contexts and what kinds of partnerships with the smart wearable were perceived by the participants. In addition, we reflect on the design issues that led to the mismatch between our design intentions and people’s actual use experiences. We discuss how these results have deepened our understanding of human-wearable partnerships in the context of stress management and the usability issues that might hinder the expression and acceptance of smart wearables designed as partners. We end the discussion by reflecting on the implications of smart wearables as partners in mental healthcare. Show less
Galbally, M.; Watson, S.J.; Lappas, M.; Kloet, E.R. de; Wyrwoll, C.S.; Mark, P.J.; Lewis, A.J. 2022
In examining maternal depression, placental 11 beta-HSD2 mRNA expression and offspring cortisol regulation as a potential fetal programming pathway in relation to later child emotional disorders,... Show moreIn examining maternal depression, placental 11 beta-HSD2 mRNA expression and offspring cortisol regulation as a potential fetal programming pathway in relation to later child emotional disorders, it has become clear that sex differences may be important to consider. This study reports on data obtained from 209 participants in the Mercy Pregnancy and Emotional Wellbeing Study (MPEWS) recruited before 20 weeks of pregnancy. Maternal depressive disorders were diagnosed using the SCID-IV and maternal childhood trauma using the Childhood Trauma Questionnaire. Placental 11 beta-HSD2 mRNA was measured using qRT-PCR. For assessment of stressinduced cortisol reactivity, salivary cortisol samples were taken at 12 months of age. At 4 years of age, measurement of Childhood Emotional Disorders (depression and anxiety) was based on maternal report using the Preschool Age Psychiatric Assessment (PAPA) and internalizing symptoms using the Child Behavior Checklist (CBCL). Maternal depression in pregnancy and postpartum, and infant cortisol reactivity, was associated with internalizing symptoms for females only. For female offspring only, increased 12-month cortisol reactivity was also associated with increased emotional disorders at 4 years of age; however, there was no association with placental 11 beta-HSD2 mRNA expression. In females only, the combination of lower placental 11 beta-HSD2 mRNA expression and higher cortisol reactivity at 12 months of age predicted increased internalising problems. These findings suggest there may be sex differences in prenatal predictors and pathways for early childhood depression and anxiety symptoms and disorder. Show less
Background: Learned placebo effects induced by pharmacological conditioning affect immune and endocrine outcomes and may offer new possibilities for clinical applications. Whether or not cortisol... Show moreBackground: Learned placebo effects induced by pharmacological conditioning affect immune and endocrine outcomes and may offer new possibilities for clinical applications. Whether or not cortisol is subject to this type of associative learning processes, and whether conditioning may affect responses to stress, is currently unclear.Method: A randomized placebo-controlled trial was conducted in 48 healthy young women. During acquisition, participants received a pill containing either 100 mg hydrocortisone (unconditioned stimulus) or placebo, paired with a gustatory conditioned stimulus on three consecutive days. During evocation, all participants received placebo paired with the conditioned stimulus, again on three consecutive days. During the third evocation trial, participants underwent a psychosocial stress task. The main outcome parameter salivary cortisol and secondary outcome parameters salivary alpha-amylase, self-reported positive affect and tension, heart rate, and skin conductance level were measured at several time points.Results: Significant baseline group differences on cortisol were found at several time points, which complicate the interpretation of group differences. During the first evocation session, the conditioned group showed a moderately smaller cumulative decrease in salivary cortisol from baseline than the placebo control group. No significant differences were found between the groups on cortisol during the second and third evocation or in response to stress, nor on other outcome measures.Conclusion: Although the results provide potential further indications for effects of conditioning on cortisol, baseline differences make it impossible to draw clear conclusions. No indications for possible effects of conditioning on the cortisol stress response or autonomous or affective responses to stress were found. Show less
Beurden, M. van; Brouwer, A.M.; Baardewijk, J.U. van; Binsch, O.; Vermetten, E.; Roijendijk, L. 2020
Feedback of physiological responses have a great potential to support virtual training paradigms aimed to increase cognitive task performance under stressful threatening conditions. In the current... Show moreFeedback of physiological responses have a great potential to support virtual training paradigms aimed to increase cognitive task performance under stressful threatening conditions. In the current study, we examined the sensitivity of a range of physiological indicators derived from electrodermal activity (EDA), blood pressure (BP) and heart rate (HR) to measure stress as induced by the threat of an electric shock (ES). In contrast to previous work that studied physiological stress responses compared to a rest condition, we compared conditions with high cognitive load combined with stress caused by threat of an ES, to conditions with high cognitive load without such stress. Twenty-five participants performed a cognitively demanding task in an experimental setup. At certain 10 s time intervals, indicated by a continuous tone, participants were either asked to do their best and increase cognitive task performance (non-threat condition), or they were told that they could receive an ES during this interval if cognitive task performance was not high enough (threat condition). Physiological measures, task performance and self-reported measures of stress and workload were analysed. Task performance and self-reported measures of stress and workload were roughly the same in both conditions. Especially EDA measures were affected by the threat of an ES. Threat and non-threat conditions could be distinguished with an across-participant classifier using EDA and BP features with an accuracy of 70%. These results suggest that EDA and BP can be used to evaluate stress coping training paradigms or to individually adapt the stress levels in virtual training environments. Show less
Our research group recently published a positive association between early postoperative pain and 30-day postoperative complications in a broad surgical population. To investigate whether... Show moreOur research group recently published a positive association between early postoperative pain and 30-day postoperative complications in a broad surgical population. To investigate whether heterogeneity of the population and surgical procedures influenced these results, we explored this association in a homogenous surgical population. A secondary analysis of the LEOPARD-2 (NCT02146417) and RELAX-1 study (NCT02838134) in laparoscopic donor nephrectomy patients (n = 160) was performed. Pain scores on the postanesthesia care unit and postoperative day (POD) 1 and 2 were compared between patients with infectious, noninfectious, and no complications 30 days after surgery. Patients who developed infectious complications had significantly higher pain scores on POD1 and 2 (6.7 +/- 2.1 and 6.4 +/- 2.8) than patients without complications (4.9 +/- 2.2 and 4.1 +/- 1.9), respectively (P= 0.006 andP= 0.000). Unacceptable pain (numeric rating scale [NRS] >= 6) on POD1 was reported by 72% of patients who developed infectious complications, compared to 38% with noninfectious complications and 30% without complications (P= 0.018). This difference was still present on POD2 at 67% with infectious complications, 21% with noninfectious, and 40% without complications (P= 0.000). Multiple regression analysis identified unacceptable pain (numeric rating scale >= 6) on POD2 as a significant predictor for 30-day infectious complications (odds ratio 6.09,P= 0.001). Results confirm the association between early postoperative pain and 30-day infectious complications in a separate, homogenous surgical population. Further clinical trials should focus on finetuning of postoperative analgesia to elucidate the effects on the endocrine and immune response, preserve immune homeostasis, and prevent postoperative infectious complications. Show less
Kumar, M.; Dijk, E.H.C. van; Raman, R.; Mehta, P.; Boon, C.J.F.; Goud, A.; ... ; Chhablani, J. 2020
Background To compare vision-related quality of life (VRQOL) between acute and chronic Central serous chorioretinopathy (CSC) and correlate this with Cohen's Perceived Stress Scale (PSS)... Show moreBackground To compare vision-related quality of life (VRQOL) between acute and chronic Central serous chorioretinopathy (CSC) and correlate this with Cohen's Perceived Stress Scale (PSS) questionnaire. Methods Patients who were diagnosed with both acute and chronic CSC were recruited in this study. Vision-related quality of life (VRQOL) was assessed with Rasch revised National Eye Institute Visual Functioning Questionnaire 25 (NEI-VFQ25) and perceived stress with Cohen's PSS questionnaire in 118 subjects with either acute or chronic CSC. The quality of life score was compared between patients with acute and chronic CSC. Correlations between the functional score and visual acuity (VA), stage of CSC, and stress were studied. Results There was no significant difference in VRQOL between Acute and Chronic CSC. In Acute CSC, affected eye VA correlated significantly with near vision question of the visual function subscale. Better eye VA correlated significantly with distance vision, social function, role limitation and dependency of the socioeconomic subscale. In chronic CSC, affected eye VA correlated with social function question of the socioemotional subscale and the better eye VA correlated with driving and distance vision of the visual function subscale. No other significant correlations with VA were noted. No correlations were observed between outcome of Cohen's PSS questionnaire and NEI-VFQ25 scores of acute and chronic CSC. Conclusion The VRQOL is similar between acute and chronic CSC. Perceived stress was not found to influence the VRQOL in CSC. Show less
Direct interaction with students operates as the main source of teachers’ job satisfaction as well as a cause of feelings of distress. Teaching student-teacher appropriate coping strategies might... Show moreDirect interaction with students operates as the main source of teachers’ job satisfaction as well as a cause of feelings of distress. Teaching student-teacher appropriate coping strategies might make direct interaction with students a source of greater job satisfaction. A typology has been developed of student-teachers’ responses to stressful classroom events in secondary education with four types of coping: “Varying”, “Being annoyed”, “Problem-solving” and “Avoiding” varying along two underlying dimensions: avoidance-approach and calmness-agitation. The coping types particularly differed in the way student-teachers approached, tolerated, avoided or ignored the classroom event, how agitated they were and the length of the coping response. Implications for teacher education are discussed to support student-teachers with more approach-coping strategies instead of avoidance-coping strategies. Show less
The ventral tegmental area dopamine (VTA-DA) mesolimbic circuit processes emotional, motivational, and social reward associations together with their more demanding cognitive aspects that involve... Show moreThe ventral tegmental area dopamine (VTA-DA) mesolimbic circuit processes emotional, motivational, and social reward associations together with their more demanding cognitive aspects that involve the mesocortical circuitry. Coping with stress increases VTA-DA excitability, but when the stressor becomes chronic the VTA-DA circuit is less active, which may lead to degeneration and local microglial activation. This switch between activation and inhibition of VTA-DA neurons is modulated by e.g. corticotropin-releasing hormone (CRH), opioids, brain-derived neurotrophic factor (BDNF), and the adrenal glucocorticoids. These actions are coordinated with energy-demanding stress-coping styles to promote behavioral adaptation. The VTA circuits show sexual dimorphism that is programmed by sex hormones during perinatal life in a manner that can be affected by glucocorticoid exposure. We conclude that insight in the role of stress in VTA-DA plasticity and connectivity, during reward processing and stress-coping, will be helpful to better understand the mechanism of resilience to breakdown of adaptation. Show less
Exposure to traumatic stress increases the odds of developing a broad range of psychiatric conditions. Genetic studies targeting multiple stress-related quantitative phenotypes may shed light on... Show moreExposure to traumatic stress increases the odds of developing a broad range of psychiatric conditions. Genetic studies targeting multiple stress-related quantitative phenotypes may shed light on mechanisms underlying vulnerability to psychopathology in the aftermath of stressful events. We applied a multivariate genome-wide association study (GWAS) to a unique military cohort (N = 583) in which we measured biochemical and behavioral phenotypes. The availability of pre- and post-deployment measurements allowed to capture changes in these phenotypes in response to stress. For genome-wide significant loci, we performed functional annotation, phenome-wide analysis and quasi-replication in PTSD case-control GWASs. We discovered one genetic variant reaching genome-wide significant association, surviving permutation and sensitivity analyses (rs10100651, p = 9.9 x 10(-9)). Functional annotation prioritized the genes INTS8 and TP53INP1. A phenome-wide scan revealed a significant association of these same genes with sleeping problems, hypertension and subjective well-being. Finally, a targeted lookup revealed nominally significant association of rs10100651 in a PTSD case-control GWAS in the UK Biobank (p = 0.02). We provide comprehensive evidence from multiple resources hinting at a role of the highlighted genetic variant in the human stress response, marking the power of multivariate genome-wide analysis of quantitative measures in stress research. Future genetic and functional studies can target this locus to further assess its effects on stress mediation and its possible role in psychopathology or resilience. (C) 2019 Elsevier B.V. and ECNP. All rights reserved. Show less
The forced swim test (FST) for rodents does not model despair or helplessness. It also is not a read-out for depression, anxiety, psychomotor retardation or autism, because these are... Show moreThe forced swim test (FST) for rodents does not model despair or helplessness. It also is not a read-out for depression, anxiety, psychomotor retardation or autism, because these are anthropomorphic interpretations of the rodent's acquired immobility. Rather, the transition from swimming to immobility allows to examine the mechanistic underpinning of coping with inescapable stressors. However, in a recent detailed analysis of the FST application over the past 40 years, we noted a dramatic surge in the use of this test to phenotype animals as 'depressed'. As a follow up to that report, we now present an analysis of the use of the FST over the past three years. This literature analysis shows that the popularity of the EST is still increasing and that the majority of researchers qualifies the rodent's floating response as depressive-like behavior. However, over the past few years we also note a trend to interpret immobility rather as the expression of a coping strategy. In view of this result, we have sent a poll to the relevant authors to learn how consistent they are in naming FST behavior. Remarkably, we find a dramatic inverse correlation between their first qualification of acquired immobility as depressive-like behavior towards their current interpretation as coping strategy. In this contribution we have embedded our literature analysis and poll results in an update on the management of coping with inescapable stressors by processing in prefrontal cortical circuitry and glucocorticoid feedback. Show less
The forced swim test (FST) for rodents does not model despair or helplessness. It also is not a read-out for depression, anxiety, psychomotor retardation or autism, because these are... Show moreThe forced swim test (FST) for rodents does not model despair or helplessness. It also is not a read-out for depression, anxiety, psychomotor retardation or autism, because these are anthropomorphic interpretations of the rodent’s acquired immobility. Rather, the transition from swimming to immobility allows to examine the mechanistic underpinning of coping with inescapable stressors. However, in a recent detailed analysis of the FST application over the past 40 years, we noted a dramatic surge in the use of this test to phenotype animals as ‘depressed’. As a follow up to that report, we now present an analysis of the use of the FST over the past three years. This literature analysis shows that the popularity of the FST is still increasing and that the majority of researchers qualifies the rodent’s floating response as depressive-like behavior. However, over the past few years we also note a trend to interpret immobility rather as the expression of a coping strategy. In view of this result, we have sent a poll to the relevant authors to learn how consistent they are in naming FST behavior. Remarkably, we find a dramatic inverse correlation between their first qualification of acquired immobility as depressive-like behavior towards their current interpretation as coping strategy. In this contribution we have embedded our literature analysis and poll results in an update on the management of coping with inescapable stressors by processing in prefrontal cortical circuitry and glucocorticoid feedback. Show less
Corticosteroid hormones act in the brain to support adaptation to stress via binding to mineralocorticoid and glucocorticoid receptors (MR and GR). These receptors act in large measure as... Show moreCorticosteroid hormones act in the brain to support adaptation to stress via binding to mineralocorticoid and glucocorticoid receptors (MR and GR). These receptors act in large measure as transcription factors. Corticosteroid effects can be highly divergent, depending on the receptor type, but also on brain region, cell type, and physiological context. These differences ultimately depend on differential interactions of MR and GR with other proteins, which determine ligand binding, nuclear translocation, and transcriptional activities. In this review, we discuss established and potential mechanisms that confer receptor and cell type-specific effects of the MR and GR-mediated transcriptional effects in the brain. Show less
Psychotic depression is characterized by elevated circulating cortisol, and high daily doses of the glucocorticoid/progesterone antagonist mifepristone for 1 week are required for significant... Show morePsychotic depression is characterized by elevated circulating cortisol, and high daily doses of the glucocorticoid/progesterone antagonist mifepristone for 1 week are required for significant improvement. Using a rodent model, we find that such high doses of mifepristone are needed because the antagonist is rapidly degraded and poorly penetrates the blood-brain barrier, but seems to facilitate the entry of cortisol. We also report that in male C57BL/6J mice, after a 7-day treatment with a high dose of mifepristone, basal blood corticosterone levels were similar to that of vehicle controls. This is surprising because after the first mifepristone challenge, corticosterone remained elevated for about 16 h, and then decreased towards vehicle control levels at 24 h. At that time, stress-induced corticosterone levels of the 1xMIF were sevenfold higher than the 7xMIF group, the latter response being twofold lower than controls. The 1xMIF mice showed behavioral hyperactivity during exploration of the circular hole board, while the 7xMIF mice rather engaged in serial search patterns. To explain this rapid reset of corticosterone secretion upon recurrent mifepristone administration, we suggest the following: (i) A rebound glucocorticoid feedback after cessation of mifepristone treatment. (ii) Glucocorticoid agonism in transrepression and recruitment of cell-specific coregulator cocktails. (iii) A more prominent role of brain MR function in control of stress circuit activity. An overview table of neuroendocrine MIF effects is provided. The data are of interest for understanding the mechanistic underpinning of stress system reset as treatment strategy for stress-related diseases. Show less
