Dysfunctional Stress Responses Research Articles

Autonomic nervous system and endocrine system response to upper or lower cervical spine mobilization in males with persistent post-concussion symptoms: a proof-of-concept trial

ABSTRACT Introduction The peripheral stress response, consisting of the autonomic nervous system (ANS) and hypothalamic pituitary adrenal-axis (HPA-axis), functions to maintain homeostasis in response to stressors. Cervical spine manual therapy has been shown to differentially modulate the stress response in healthy populations. No study has investigated whether cervical spine mobilizations can differentially modulate the stress response in individuals with persistent post-concussion symptoms (PPCS), a population characterized by a dysfunctional stress response. Methods A randomized, controlled, parallel design trial was performed to investigate whether upper or lower cervical spine mobilization can differentially modulate components of the stress response in individuals with PPCS. The outcomes were salivary cortisol (sCOR) concentration (primary) and the HRV metric, rMSSD, measured with a smartphone application (secondary). Nineteen males diagnosed with PPCS, aged 19–35, were included. Participants were randomly assigned into either intervention group, upper (n = 10) or lower (n = 9) cervical spine mobilization. Each outcome was collected at different time points, pre- and post-intervention. Statistical analyses were performed using the Friedman’s Two-Way ANOVA, Mann-Whitney U test, and Wilcoxon Signed Rank Test. Results There was a statistically significant within-group reduction in sCOR concentration 30 minutes following lower cervical spine mobilizations and statistically significant within-group increase in rMSSD 30 minutes following upper cervical spine mobilizations. Conclusion The results of this trial provide preliminary evidence for cervical spine mobilizations to differentially modulate components of the stress response at specific time points. Understanding the mechanisms of the effect of cervical spine mobilizations on the stress response provides a novel rationale for selecting cervical spine mobilizations to rehabilitate individuals with PPCS.

Adult-onset dominant muscular dystrophy in Greek families caused by Annexin A11.

ObjectiveMutations in the prion‐like domain of RNA binding proteins cause dysfunctional stress responses and associated aggregate pathology in patients with neurogenic and myopathic phenotypes. Recently, mutations in ANXA11 have been reported in patients with amyotrophic lateral sclerosis and multisystem proteinopathy. Here we studied families with an autosomal dominant muscle disease caused by ANXA11:c.118G > T;p.D40Y.MethodsWe performed deep phenotyping and exome sequencing of patients from four large Greek families, including seven affected individuals with progressive muscle disease but no family history of multi‐organ involvement or ALS.ResultsIn our study, all patients presented with an autosomal dominant muscular dystrophy without any Paget disease of bone nor signs of frontotemporal dementia or Parkinson's disease. Histopathological analysis showed rimmed vacuoles with annexin A11 accumulations. Electron microscopy analysis showed myofibrillar abnormalities with disorganization of the sarcomeric structure and Z‐disc dissolution, and subsarcolemmal autophagic material with myeloid formations. Molecular genetic analysis revealed ANXA11:c.118G > T;p.D40Y segregating with the phenotype.InterpretationAlthough the pathogenic mechanisms associated with p.D40Y mutation in the prion‐like domain of Annexin A11 need to be further clarified, our study provides robust and clear genetic evidence to support the expansion of the phenotypic spectrum of ANXA11.

Dysfunction of the stress response in individuals with persistent post-concussion symptoms: a scoping review

Background Preliminary evidence suggests that individuals with persistent post-concussion symptoms (PPCS) have a dysfunctional stress response, consisting of the autonomic nervous system (ANS) and hypothalamic pituitary adrenal-axis (HPA-axis). Objectives This review aims to explore the extent of evidence for dysfunction of the stress response in individuals with PPCS by individually mapping the literature surrounding quantifiable changes of the (1) ANS and (2) HPA-axis using non-invasive and clinical tools, and highlighting any (3) knowledge gaps. Methods Nine electronic databases and grey literature were searched on the 1st of June 2021 and 4th of October 2021. Studies were included if their population was classified with PPCS, and their study stated at least one quantifiable marker of the ANS or HPA-axis using non-invasive and clinical tools. Relevant studies were screened, and data extracted. Results A total of 37 articles were included in this scoping review. The majority of studies assessed quantifiable markers of the ANS (n = 34), in comparison to the HPA-axis (n = 2), and ANS and HPA-axis (n = 1). The most common quantifiable markers of the ANS included heart rate (n = 20), blood pressure (n = 16), and heart rate variability (n = 10). Cortisol was the only included quantifiable marker of the HPA-axis (n = 2). Conclusions Most of the evidence in this review supports quantifiable dysfunction of the ANS in those with PPCS. Further research is required investigating quantifiable dysfunction of the HPA-axis, and subsequently ANS and HPA-axis in unison, in those with PPCS.

Sprint Zeal or Sprint Fatigue? The Benefits and Burdens of Agile ISD Practices Use for Developer Well-Being

Are agile information systems development practices (AISDPs), such as pair programming or daily stand-ups, universally beneficial to developer well-being? Given that agile information systems development project success is only as good as its developers’ productiveness, taking care of developer well-being is of utmost importance to organizations. Using daily survey responses of 131 agile developers spread over two workweeks, we show that the daily use of AISDP is a double-edged sword rather than a silver bullet. Although AISDPs can be motivating and activate energy resources on some days, they can be disturbing and deplete energy on others—two stress responses with opposing effects on developer well-being. As a potential antidote to the detrimental effects of AISDP, we investigate the moderating role of information technology (IT) mindfulness, a dynamic trait that captures the mindful usage of IT. We find that IT mindfulness can serve as a facilitator of positive stress responses and as a buffer against negative stress responses. A key takeaway of this study is in finding ways to influence developers (via awareness programs, time-sensitive recovery interventions, or mindfulness practices) to increase the functional and decrease the dysfunctional stress responses from daily AISDP use.

Dysfunction of the stress response in individuals with persistent post-concussion symptoms: a scoping review protocol

Background 10-15% of individuals who sustain a concussion develop persistent post-concussion symptoms (PPCS). Presently, there is no consensus regarding the pathophysiology of PPCS. Preliminary evidence suggests that individuals with PPCS have either a dysfunctional autonomic nervous system (ANS) or hypothalamic-pituitary-adrenal axis (HPA-axis). The ANS and HPA-axis collectively make up the two arms of the peripheral stress response. In the presence of a stressor, the two arms work interchangeably to return the body back to homeostasis. With concussion as the stressor, it is plausible that the development and maintenance of PPCS are due to a dysfunctional stress response. Only one study has explored the relationship between PPCS and the two arms of the stress response (ANS and HPA-axis) in combination, which presents a clear gap in the literature. Objective The proposed protocol aims to determine the extent of evidence for dysfunction of the stress response in individuals with PPCS. This review will individually map the literature surrounding quantifiable changes in the (1) ANS and (2) HPA-axis in individuals with PPCS. The review will also highlight any (3) knowledge gaps in this emerging field of research. Methods A scoping review study design has been chosen to facilitate a thorough literature search on this broad exploratory topic. The scoping review proposed will follow the recommended methodological guidelines. Conclusion Understanding the potential role of a dysfunctional stress response in those with PPCS will create more effective treatment pathways and reduce the chronicity of this condition.

717 Dysfunctional stress response in psoriatic keratinocytes

717 Dysfunctional stress response in psoriatic keratinocytes

Transtornos relacionados ao uso de álcool e as mulheres: impacto nos circuitos integrativos e de neurorregulação do estresse

Dysfunctional stress response can play a key role in some mental disorders. An increasing number of studies have demonstrated sex differences in the prevalence of stress-related disorders. In particular, women with alcohol use disorders (AUDs) present different negative outcomes whe compared to men in terms of brain function e neuroadaptative mechanisms. Alcohol consumption has been associated with subtle, long-term hypothalamic-hypophysis-adrenal (HPA) axis alterations, affecting the adaptive response of stress neuroregulatorycircuits. Future research in this field may positively influence the development of treatment strategies.

Exhaustion-related changes in cardiovascular and cortisol reactivity to acute psychosocial stress

Prior findings indicate that individuals scoring high on vital exhaustion show a dysfunctional stress response (DSR), that is, reduced cortisol reactivity and habituation to psychosocial stressors. The main aim of the present study was to examine whether a DSR may be a vulnerability factor in exhaustion disorder (ED). We examined whether a DSR is present during the early stages of ED, and still is present after recovery. Three groups were studied: 1. Former ED patients (n=14); 2. persons who during the past 6month had experienced stress at work and had a Shirom–Melamed Burnout Questionnaire (SMBQ) score over 3.75, considered to indicate a pre-stage of ED (n=17); 3. persons who had not experienced stress at work during the past 6months and had a SMBQ score below 2.75 (n=20). The participants were exposed twice to a virtual version of the Trier Social Stress Test (V-TSST), during which salivary cortisol samples were collected. In addition, high frequency heart rate variability (HF-HRV), heart rate (HR), t-wave amplitude (TWA), and α-amylase were assessed to examine stress reactivity and habituation in the autonomic nervous system (ANS).The initial analyses showed clear hypothalamic–pituitary–adrenal (HPA) axis and sympathetic nervous system (SNS) activations in both V-TSST sessions, together with habituation of cortisol and heart rate in the second session, but without any significant group differences. However, the former ED patients showed considerable variation in self-reported signs of exhaustion (SMBQ). This led us to assign former ED patients with lower ratings into the low SMBQ group (LOWS) and those with higher ratings to the high SMBQ group (HIGHS). When repeating the analyses a different picture emerged; the HIGHS showed a lower cortisol response to the V-TSST than did the LOWS. Both groups' cortisol response habituated to the second V-TSST session. The ANS responses did not differ between the two groups.Thus, persons in a pre-stage of ED and unrecovered former ED patients showed signs of DSR, in contrast to healthy controls and recovered former ED patients. The results may be interpreted as indicating that DSR in the HPA axis is present early on in the stress process, but subsides after successful recovery.

Brain manifestation and modulation of pain from myofascial trigger points

The brain plays a prominent role in the generation and modulation of pain. It contains powerful endogenous pain modulatory systems that can be engaged in a beneficial way by therapeutical intervention. In contrast, pain chronification is associated with maladaptive structural and functional changes that may shift the balance of the modulatory systems. Although pain from myofascial trigger points (MTrPs) is highly prevalent, little is known about its brain manifestations and modulation. Recent neuroimaging data suggest that hyperalgesia from MTrPs is processed in similar regions as hyperalgesia from other pain conditions. However, abnormal hippocampal hypoactivity suggests that dysfunctional stress responses may play an important role in the generation and maintenance of hyperalgesia from MTrPs. Other data suggest that short-term pain relief obtained with intramuscular electrostimulation within an MTrP is partially due to descending pain inhibitory mechanisms.

Integrated assessment of emotional distress after work‐related accidents

AbstractWork accidents can be traumatic events that might give rise to a variety of dysfunctional stress responses. An integrated assessment of stress responses after work‐related trauma is considered as a valuable approach in clinical practice. The purpose of the present study was to assess affective adjustment after work‐related accidents using a multidimensional assessment. Fourteen males who had experienced work‐related accidents and 13 male controls were assessed using self‐report instruments and the recording of skin conductance response and the startle reflex during the viewing of standardized trauma‐related and trauma‐unrelated pictures. Participants who underwent a work accident reported more severe maladjustment symptoms than controls, as indicated by higher Post‐traumatic stress disorder Symptom Scale (PSS) scores. Moreover, participants with higher PSS scores showed more severe depressive symptomatology and general psychopathology, and lower psychophysiological reactivity than participants with lower PSS scores. Long‐lasting maladjustment problems after work‐related accidents influence various affective domains even many years after the traumatic event. In those individuals who showed higher post‐stress symptoms, an integrated assessment highlights a lack of concordance between self‐reported symptoms and physiological activation. Copyright © 2008 John Wiley & Sons, Ltd.

Translation arrest and ribonomics in post‐ischemic brain: layers and layers of players

A persistent translation arrest (TA) correlates precisely with the selective vulnerability of post-ischemic neurons. Mechanisms of post-ischemic TA that have been assessed include ribosome biochemistry, the link between TA and stress responses, and the inactivation of translational components via sequestration in subcellular structures. Each of these approaches provides a perspective on post-ischemic TA. Here, we develop the notion that mRNA regulation via RNA-binding proteins, or ribonomics, also contributes to post-ischemic TA. We describe the ribonomic network, or structures involved in mRNA regulation, including nuclear foci, polysomes, stress granules, embryonic lethal abnormal vision/Hu granules, processing bodies, exosomes, and RNA granules. Transcriptional, ribonomic, and ribosomal regulation together provide multiple layers mediating cell reprogramming. Stress gene induction via the heat-shock response, immediate early genes, and endoplasmic reticulum stress represents significant reprogramming of post-ischemic neurons. We present a model of post-ischemic TA in ischemia-resistant neurons that incorporates ribonomic considerations. In this model, selective translation of stress-induced mRNAs contributes to translation recovery. This model provides a basis to study dysfunctional stress responses in vulnerable neurons, with a key focus on the inability of vulnerable neurons to selectively translate stress-induced mRNAs. We suggest a ribonomic approach will shed new light on the roles of mRNA regulation in persistent TA in vulnerable post-ischemic neurons.

CRF1 receptor antagonists: treatment of stress-related disorders

Adaptive responding to stressors is of fundamental importance to the survival of the species. Aberrant hyperactivation of corticotropin releasing factor type 1 (CRF1) receptors in dysfunctional stress response system (SRS) pathways may contribute to stress-related psychopathology and therefore CRF1 receptor antagonists (CRAs) may be useful in their treatment. The status of nonpeptidic, orally active, brain-penetrating CRAs being developed for the treatment of depression, anxiety, irritable bowel syndrome and drug abuse is reviewed.

A chronic dysfunctional stress response can cause stroke by stimulating platelet activation, migraine, and hypertension

A hypothesis is presented on the mechanism of acute intracranial occlusion. The hypothesis is that a chronic dysfunctional response to stress can include migraine, hypertension and systemic platelet activation (a hypercoagulable state). Stress is defined as the perception of excessive threats or demands. Migraine, hypertension, and platelet activation constitute a physiological triad that exists as a distinct entity and can undergo sudden provoked or unprovoked worsening, causing acute stroke. The hypertension and headache may not be apparent in every stroke, much as headache is absent in acephalgic migraine. In support of this idea, a literature review is undertaken which leads to the conclusion that the labile rise in blood pressure and headache often seen with acute stroke are unlikely to be caused by the stroke. Systemic platelet activation has been documented in both migraine and stroke and is the missing piece of the puzzle. Migraine (or non-specific headache) and hypertension are markers of co-existing platelet activation, the hypercoagulable state which causes stroke. Migraine, and, putatively, hypertension and platelet activation, are driven by overactive pacemaker cells in the dorsal raphe nucleus of the midbrain, the nucleus which mediates one arm of the physiologic response to stress. A therapeutic prediction is made that drugs such as ethosuximide, which block the low voltage-activated T-type calcium channel, which is one of the ion channels implicated in the generation of pacemaker currents in the dorsal raphe nucleus, would be useful in stroke prevention.

Why do patients meeting criteria for borderline personality disorder deliberately harm themselves? Some hypothesised neurobiological correlates

The majority of patients meeting criteria for borderline personality disorder deliberately harm themselves at some time in their lives. This deliberate self-harm is nearly always subsequent to interpersonal loss. This paper postulates that the physiological arousal, which precedes deliberate self-harm, has a distinctive pattern specific to borderline personality disorder. The clinical manifestations are: baseline distress, followed by an environmental trigger factor (separation), which sets off an acute response of increasing distress, usually accompanied by ruminations. This develops into an intensely disagreeable subjective state, with simultaneous cutaneous anaesthesia or dissociative symptoms. It is this highly unpleasant state which is rapidly and very effectively relieved by soft tissue injury. In borderline personality disorder a dysfunctional stress response is hypothesised to underlie the acute subjective distress and the accompanying somatic symptoms that occur prior to deliberate self-harm. Central neuro-humoral mechanisms, via peripheral afferent stimulation as a result of soft tissue injury, are hypothesised to relieve the subjective tension by re-establishing homoeostasis. This paper examines the underlying biological aspects of separation distress and the mechanism by which it is relieved. In this sense separation distress is conceptualised in behavioural terms as the reaction to an environmental event. The psychological mechanisms of attachment and separation are not examined. Deliberate self-harm in borderline personality disorder may thus be understood as a coping mechanism, a potent means of overcoming unbearable subjective distress. A clearer understanding of the mechanisms of this behaviour may lead to more effective and compassionate treatments.

Differential development of the stress response in congenital learned helplessness

Early in the development of the hypothalamic-pituitary-adrenal (HPA) axis, the rat undergoes a stress hyporesponsive period of blunted responses to several Stressors including cold exposure (CE) and maternal deprivation (MD). We examined the development of the axis by monitoring adrenocorticotropin hormone (ACTH) plasma levels in an animal model of depression and/or anxiety characterized by learned helpless (LH) behavior and a dysfunctional HPA axis in adult life. On postnatal day 7 there was no significant difference in basal plasma ACTH levels between congenital (cLH) and controls, but cLH animals showed a blunted response to CE (P<0.001). By postnatal day 14 there was a dramatic increase in ACTH response to CE (P<0.005). On postnatal day 21 baseline ACTH and response to CE were again significantly suppressed in cLH rats. Stress responsiveness to MD was present in all groups and was insignificantly different for all ages of development between groups. These findings suggest that rats with congenital learned helplessness undergo a differential response in the development of the HPA axis in that the axis was hypersensitive at postnatal day 14 and became hyporesponsive beyond day 14 and this may, in part, account for the dysfunctional stress response observed during adulthood.