Stress-The International Journal on the Biology of Stress最新文献

Aberrant functioning of the hypothalamic-pituitary-adrenal (HPA) axis is a hallmark of conditions such as depression, anxiety disorders, and post-traumatic stress disorder. Early-life adversity and genetic variation can interaction to disrupt HPA axis regulation, potentially contributing to certain forms of psychopathology. This study employs a rhesus macaque model to investigate how early parental neglect interacts with a single nucleotide polymorphism within the promoter region of the corticotropin-releasing hormone (CRH-248) gene, impacting the development of the HPA axis. For the initial six months of life, 307 rhesus monkey infants (n = 146 females, n = 161 males) were either reared with their mothers (MR) in conditions emulating the natural environment (control group) or raised without maternal care in groups with constant or 3-hours daily access to same-aged peers (NR). Blood samples collected on days 30, 60, 90, and 120 of life under stressful conditions were assayed for plasma cortisol and adrenocorticotropic hormone (ACTH) concentrations. Findings revealed that NR subjects exhibited a significant blunting of both ACTH and cortisol concentrations. Notably, there was a gene-by-environment interaction observed for ACTH and cortisol levels, with NR subjects with the polymorphism displaying higher ACTH concentrations and lower cortisol concentrations. To the extent that these results generalize to humans, they suggest that early parental neglect may render individuals vulnerable to HPA axis dysfunction, a susceptibility that is modulated by CRH-248 genotype-a gene-by-environment interaction that leaves a lasting developmental signature.

Laboratory stress tasks are necessary to closely investigate the stress response in a controlled environment. However, to our knowledge, no study has tested whether participating in such tasks can pose any daily life adverse effect. Fifty-three healthy participants (46 women) took part in a laboratory session where stress was induced using a typical psychosocial stressor: the repeated Montreal Imaging Stress Task (rMIST). Average levels of negative affect (NA), heart rate (HR), root mean square of successive differences (RMSSD), and skin conductance level (SCL), as well as reactivity across all these parameters as measured with the experience sampling method (ESM) in the four days prior to the laboratory session were compared with the four days following the session. We also assessed whether vulnerability to psychopathology moderated these associations. Findings showed that the task did not pose any significant adverse effect on participants. However, there was an unexpected increase in average RMSSD and a decrease in average SCL pre- to post- task. In addition, more vulnerable individuals were more likely to experience an increase in average levels of NA in the days following the task compared to the days preceding it. Our findings suggest that laboratory stress tasks may pose a significant risk to more vulnerable individuals.

Stress has been linked to the development of irritable bowel syndrome (IBS), and various methods have been explored to model IBS in combination with other stimuli. However, it remains unclear whether stress alone can induce IBS in animals. This study aimed to investigate the impact of chronic unpredictable mild stress (CUMS) on gastrointestinal sensation and function in mice and assess the potential of CUMS as a modeling approach for IBS. To evaluate the mice's behavior, we conducted open field test, sucrose preference test and weighed the mice, revealing that CUMS indeed induced anxiety and depression in the mice and caused weight loss. Further analyses, including fecal analysis, a total gastrointestinal transport test, and a colon propulsion test, demonstrated that CUMS led to abnormal defecation and disruptions in gastrointestinal motility in the mice. Additionally, the abdominal withdrawal reflex test indicated an increase in visceral sensitivity in CUMS-exposed mice. Histological examination using hematoxylin and eosin staining revealed no significant histological alterations in the colons of CUMS-exposed mice, but it did show a minor degree of inflammatory cell infiltration. In summary, the findings suggest that CUMS can replicate IBS-like symptoms in mice, offering a novel top-down approach to modeling IBS.

Acute stress has been demonstrated to affect a diverse array of attentional processes, one of which is selective attention. Selective attention refers to the cognitive process of deliberately allocating attentional resources to a specific stimulus, while ignoring other, distracting stimuli. While catecholamines have been shown to narrow attention, investigations on the influence of the stress hormone cortisol have yielded ambiguous results. We conducted two separate studies utilizing different laboratory stress induction paradigms to examine if cortisol influences the ability to selectively attend to local or global elements of a visual stimulus. In Study 1, 72 healthy young men took part either in the stressful Socially Evaluated Cold Pressor Test (SECPT) or a non-stressful (warm water) control, before being exposed to a composite letter task (CLT). Study 2 comprised a sample of 72 healthy young men and women and made use of a modified version of the Trier Social Stress Test (TSST) as well as a non-stressful control version, the friendly-TSST (f-TSST). Via endocrine, physiological, and subjective markers, we confirmed a successful stress induction. As verified with Bayesian statistics, stress did not affect selective attention in neither of the two studies. Furthermore, we were able to replicate the previously demonstrated absence of global precedence for composite figures composed of letters. Our results offer novel insights into the temporal dynamics of the effects of acute stress on attentional processes. Future studies should manipulate the timing of stress induction and investigate the effects of stress on letter vs. non-letter composite figures to shed further light on the underlying mechanisms.

Successful and efficient emotion regulation (ER) is a key mechanism for mental health. However, acute stress may impact the ability to cognitively regulate negative emotions due to its immediate effects on executive functioning. Based on previous studies, we expected that the time at which ER is tested after a stressor might have a decisive influence, with impairments in ER being more pronounced immediately after stress as compared to a later post-stress phase. To investigate such a time-dependent effect of stress on ER, we investigated 50 healthy adults (26 female) who were exposed to either the Trier Social Stress Test (n = 25) or a control condition (n = 25). Afterwards subjects conducted a cognitive ER task during which they were instructed to either regulate (cognitive reappraisal) or passively view neutral and negative visual stimuli. The ER task was divided into an early (0-20 minutes) and a late post-stress phase (20-40 minutes). Salivary cortisol and α-amylase were assessed as markers of the neuroendocrine stress response. Self-reported emotional state, the mean activity of the late positive potential measured via electroencephalogram (EEG), and corrugator electromyographic activity (EMG) were used as indices of ER. While the groups did not differ in the early post-stress phase, our results suggest a stress-related impairment in ER in the late post-stress phase. This effect was evident in all ER outcome variables (subjective rating, EEG, and EMG data). These results suggest a time-specific stress effect on cognitive reappraisal, which would have implications for reappraisal as a possible stress management technique.

Mindfulness-based interventions have become a popular means to reduce stress. However, the specific mechanisms driving observed stress reduction remain understudied. The Monitor and Acceptance Theory suggests that the cultivation of monitoring and acceptance skills are necessary moderators of practice-induced stress reduction. In the context of the ReSource Project, a large healthy adult sample underwent three 3-month mental training modules targeting either attentional (Presence module), socio-affective (Affect module) or socio-cognitive skills (Perspective module). In the current study, the development of a range of inter-individual differences in mindfulness-, interoception- and compassion-related traits - which mapped to either monitoring or acceptance categories - was tracked. The relationship of these training-induced changes with cortisol stress reactivity after the three distinct 3-month training modules was explored. We found that stress sensitivity was particularly modulated by a differential adaptivity of one cultivated attentional capacity - Attention regulation - which predicted higher cortisol reactivity after mere attention training (Presence) but was associated with lower stress-induced cortisol release after additional socio-affective and socio-cognitive practice (Affect and Perspective). However, this effect did not survive multiple comparisons correction, and analyses were limited by the sample size available. We conclude that our study provides preliminary support of the Monitor and Acceptance Theory, lending weight to the advantage of primary attentional increases in order to fully harness the beneficial effects of socio-affective training, ultimately leading to stress reduction. Although training-induced increases in acceptance were not directly shown to contribute to lowering cortisol stress reactivity, the data suggest an additional benefit of socio-affective and socio-cognitive training that is not directly captured within the current analyses. Our study corroborates the importance of going beyond the training of attention monitoring to foster stress resilience, and highlights that mental training relies on the co-development of several interacting processes to successfully attenuate stress. Further exploring the overarching concept of acceptance in future research may prove beneficial to the theoretical framework of MAT, and in understanding the processes by which stress reduction occurs.

Although dysregulated stress biology is becoming increasingly recognized as a key driver of lifelong disparities in chronic disease, we presently have no validated biomarkers of toxic stress physiology; no biological, behavioral, or cognitive treatments specifically focused on normalizing toxic stress processes; and no agreed-upon guidelines for treating stress in the clinic or evaluating the efficacy of interventions that seek to reduce toxic stress and improve human functioning. We address these critical issues by (a) systematically describing key systems and mechanisms that are dysregulated by stress; (b) summarizing indicators, biomarkers, and instruments for assessing stress response systems; and (c) highlighting therapeutic approaches that can be used to normalize stress-related biopsychosocial functioning. We also present a novel multidisciplinary Stress Phenotyping Framework that can bring stress researchers and clinicians one step closer to realizing the goal of using precision medicine-based approaches to prevent and treat stress-associated health problems.

Exposure to significant levels of stress and trauma throughout life is a leading risk factor for the development of major psychiatric disorders. Despite this, we do not have a comprehensive understanding of the mechanisms that explain how stress raises psychiatric disorder risk. Stress in humans is complex and produces variable molecular outcomes depending on the stress type, timing, and duration. Deciphering how stress increases disorder risk has consequently been challenging to address with the traditional single-target experimental approaches primarily utilized to date. Importantly, the molecular processes that occur following stress are not fully understood but are needed to find novel treatment targets. Sequencing-based omics technologies, allowing for an unbiased investigation of physiological changes induced by stress, are rapidly accelerating our knowledge of the molecular sequelae of stress at a single-cell resolution. Spatial multi-omics technologies are now also emerging, allowing for simultaneous analysis of functional molecular layers, from epigenome to proteome, with anatomical context. The technology has immense potential to transform our understanding of how disorders develop, which we believe will significantly propel our understanding of how specific risk factors, such as stress, contribute to disease course. Here, we provide our perspective of how we believe these technologies will transform our understanding of the neurobiology of stress, and also provided a technical guide to assist molecular psychiatry and stress researchers who wish to implement spatial omics approaches in their own research. Finally, we identify potential future directions using multi-omics technology in stress research.

Chronic pain is a prevalent condition with significant impacts on individuals' lives, including heightened stress and impaired physiological functioning. Given that work and family are the two main social domains where stress manifests, this study aimed to investigate the interactions between chronic pain, work-family stressors, and diurnal cortisol patterns to understand how chronic pain affects daily life and physiological stress responses. We identified 1,413 adults with chronic pain and 1,413 matched controls within MIDUS II samples to examine work-family spillover, daily work and home stressors, and cortisol levels across multiple days. The chronic pain group reported more negative work to family spillover and experienced more instances of stressful home events, particularly avoided arguments. These results align with literature suggesting chronic pain exacerbates tensions in close relationships and increases stress. The chronic pain group also had higher cortisol levels cross late-day periods, indicative of hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This dysregulation is associated with poorer health outcomes, including increased inflammation and psychological distress. We did not find any differences in previously identified cortisol profiles, which are higher-level summaries of cortisol levels within each day. We discuss why such difference might not have appeared in this sample.

Compared to the in-person Trier Social Stress Test (TSST), virtual reality (VR) variants reduce resource-intensity and improve standardization but induce stress with smaller effect sizes. However, higher cortisol reactivity is given for more immersive TSST-VRs. Immersivity depends on the VR-system, but perceived immersion may be targeted by exposure to, or interaction with the VR. We investigated whether stress reactivity towards the openly accessible OpenTSST VR can be enhanced by prior exposure to a sensorimotor game completed in VR as mediated by increased immersion. Therefore, N = 58 healthy participants underwent the OpenTSST VR or its inbuilt control condition (placebo TSST-VR, pTSST-VR). Beforehand, participants completed a sensorimotor game either in VR or in real life. Stress was measured by means of self-reports, salivary cortisol concentrations, and salivary alpha-amylase (sAA) activity. Perceived immersion was assessed with the Igroup Presence Questionnaire (IPQ). The TSST-VR-group showed higher subjective stress than the pTSST-VR-group. Even though area under the curve measures indicated significant differences in cortisol levels between TSST-VR and pTSST-VR, this effect was not replicated in omnibus-analyses. Likewise, sAA was not responsive to stress. Our data suggests the OpenTSST VR does not reliably trigger physiological stress reactivity. Likewise, participants playing the VR-game before exposure to the TSST-VR did not show enhanced stress reactivity. Importantly, playing the VR-game did not lead to increased immersion (indicated by the IPQ), either. The key question resulting from our study is which manipulation may be fruitful to obtain a comparable stress response toward the TSST-VR compared to the in-person TSST.