Stress-related Illnesses Research Articles

Aberrant anterior cingulate processing of anticipated threat as a mechanism for psychosis

Stress and abnormal stress response are associated with schizophrenia spectrum disorder (SSD), but the brain mechanisms linking stress to symptomatology remain unclear. In this study, we used a stress-based functional neuroimaging task, reverse-translated from preclinical studies, to test the hypothesis that abnormal corticolimbic processing of stressful threat anticipation is associated with psychosis and affective symptoms in SSD. Participants underwent an MRI-compatible ankle-shock task (AST) in which the threat of mild electrical shock was anticipated. We compared functional brain activations during anticipatory threat periods from N = 18 participants with SSD (10 M/8F) to those from N = 12 community controls (9 M/3F). After family-wise error correction, only one region, the ventral anterior cingulate cortex (vACC), showed significantly reduced activation compared with controls. vACC activation significantly correlated with clinical symptoms measured by the Brief Psychiatric Rating Scale total score (r = 0.54) and the psychosis subscale (r = 0.71), and inversely correlated with trait depression measured by the Maryland Trait and State Depression scale (r=-0.48). Deficient activation in vACC under stress of anticipated threat may lead to aberrant interpretation of such threat, contributing to psychosis and mood symptoms in SSD. This experimental paradigm has translational potential and may identify circuitry-level mechanisms of stress-related mental illness, leading to more targeted treatment.

A Literature Review of the Impacts of Heat Stress on Human Health across Africa

Heat stress-related illness attributed to the changing climate, particularly the more frequent extreme high temperatures, is becoming a theme of public concern, especially in the most vulnerable regions, such as the African continent. Knowledge of the existing research directions and gaps on heat stress and human health is vital for informing future strategic research foci capable of influencing policy development, planning, adaptation, and mitigation efforts. In this regard, a bibliometric analysis was conducted, with an emphasis on Africa, to assess regional research contributions to heat stress impacts on human health. The goals of the study were to review publication growth and patterns of the scientific publications and to identify key players (especially collaborating institutions and countries) and the evolution of research themes on the African continent, while paying attention to global trends and emergent hot topics and methodology of heat stress research. Using the Web of Science (WoS) and Scopus core collection databases, a structured keyword search was undertaken, which yielded 463 and 58 research publications from around the world and Africa, respectively. The retrieved scientific documents, published between 1968 and 2020, were analyzed and visualized using a bibliometric analysis technique and the VOSviewer software tool. The results indicate low statistics and slow scientific growth in publication output, with the highest peak having been reached in 2018, resulting in 13 scientific publications. While global research collaborations are successfully reflected in the literature, there is a considerable gap in understanding heat stress and related collaborations between African countries and international institutions. The review study has identified key opportunities that can benefit Africa through the expansion of the scope of heat stress and human health research on the continent. These opportunities can be achieved by closing the following research gaps: (1) vulnerability assessments within demographic classes, such as the elderly, (2) personal exposure and associated risks, (3) Urban Heat Island (UHI) evaluation for urban environments, and (4) heat adaptation research, which will enable informed and targeted preventive actions that will limit future heat health impacts. The authors opine that the pursuit of such studies will be most impactful if the current knowledge gaps are bridged through transdisciplinary research supported by local, regional, and international collaborators.

Reduced anterior cingulate cortex volume induced by chronic stress correlates with increased behavioral emotionality and decreased synaptic puncta density

Clinical and preclinical studies report that chronic stress induces behavioral deficits as well as volumetric and synaptic alterations in corticolimbic brain regions including the anterior cingulate cortex (ACC), amygdala (AMY), nucleus accumbens (NAc) and hippocampus (HPC). Here, we aimed to investigate the volumetric changes associated with chronic restraint stress (CRS) and link these changes to the CRS-induced behavioral and synaptic deficits. We first confirmed that CRS increases behavioral emotionality, defined as collective scoring of anxiety- and anhedonia-like behaviors. We then demonstrated that CRS induced a reduction of total brain volume which negatively correlated with behavioral emotionality. Region-specific analysis identified that only the ACC showed significant decrease in volume following CRS (p < 0.05). Reduced ACC correlated with increased behavioral emotionality (r = −0.56; p = 0.0003). Although not significantly altered by CRS, AMY and NAc (but not the HPC) volumes were negatively correlated with behavioral emotionality. Finally, using structural covariance network analysis to assess shared volumetric variances between the corticolimbic brain regions and associated structures, we found a progressive decreased ACC degree and increased AMY degree following CRS. At the cellular level, reduced ACC volume correlated with decreased PSD95 (but not VGLUT1) puncta density (r = 0.35, p < 0.05), which also correlated with increased behavioral emotionality (r = −0.44, p < 0.01), suggesting that altered synaptic strength is an underlying substrate of CRS volumetric and behavioral effects. Our results demonstrate that CRS effects on ACC volume and synaptic density are linked to behavioral emotionality and highlight key ACC structural and morphological alterations relevant to stress-related illnesses including mood and anxiety disorders.

Stress Among Surgeons: Sources and Determinants

A career in surgery brings significant challenges that can lead to substantial personal distress. To document the prevalence and sources of stress among surgeons working in Saudi Arabia. The survey was conducted between February and June 2019. All participants were surveyed using a self-administered questionnaire interview; it included socio-economic data, data related to work, and an International Stress Management Association stress questionnaire. A total of 357 surgeons were surveyed. Their ages ranged from 21 to 66 years old. Respondents, who expressed themselves as more likely to experience stress and more prone to stress and stress-related illness, were 156 (43.7%) and 150 (42%), respectively. The surgeons, who expressed the most stress, were neurosurgeons (73.1%), followed by urology surgeons (66.7%). Ophthalmologists experienced the least stress at 18.1% while ENT surgeons experienced the second-lowest amount of stress at 25.6%. Age, years of experience, and number of calls per month were identified as significant predictors of stress among surgeons. This study highlights high levels of occupational stress among surgeons. Self-awareness among physicians can enhance the ability to recognize their vulnerability to stress. The results of the study support the potential of mindfulness training to promote resilience during residency.

Neuroendocrine Response to Psychosocial Stressors, Inflammation Mediators and Brain-periphery Pathways of Adaptation.

Threats, challenging events, adverse experiences, predictable or unpredictable, namely stressors, characterize life, being unavoidable for humans. The hypothalamus-pituitary-adrenal axis (HPA) and the sympathetic nervous system (SNS) are well-known to underlie adaptation to psychosocial stress in the context of other interacting systems, signals and mediators. However, much more effort is necessary to elucidate these modulatory cues for a better understanding of how and why the "brain-body axis" acts for resilience or, on the contrary, cannot cope with stress from a biochemical and biological point of view. Indeed, failure to adapt increases the risk of developing and/or relapsing mental illnesses such as burnout, post-traumatic stress disorder (PTSD), and at least some types of depression, even favoring/worsening neurodegenerative and somatic comorbidities, especially in the elderly. We will review here the current knowledge on this area, focusing on works presenting the main brain centers responsible for stressor interpretation and processing, together with those underscoring the physiology/biochemistry of endogenous stress responses. Autonomic and HPA patterns, inflammatory cascades and energy/redox metabolic arrays will be presented as allostasis promoters, leading towards adaptation to psychosocial stress and homeostasis, but also as possible vulnerability factors for allostatic overload and non-adaptive reactions. Besides, the existence of allostasis buffering systems will be treated. Finally, we will suggest promising lines of future research, particularly the use of animal and cell culture models together with human studies by means of high-throughput multi-omics technologies, which could entangle the biochemical signature of resilience or stress-related illness, a considerably helpful facet for improving patients' treatment and monitoring.

Hormonal and Subjectively Perceived Stress of the Emergency Physicians of the Airborne Rescue Service

Due to their work activities, emergency physicians are regularly exposed to exceptional mental and physical situations. In order to prevent stress-related illnesses, the triggers of hormonal and subjectively perceived stress must be understood better. On a sample of emergency physicians from two air rescue services (N = 80), the cortisol awakening response (CAR) was determined on flight rescue days, clinic days, and days off. Pearson correlations showed significant connections between the CAR on flight rescue days and individual scales of the Trier Inventory for Chronic Stress (TICS) and the Perceived Stress Scale (PSS). The results indicate that a lower subjective stress level is associated with higher levels of hormonal stress. Stepwise regression analyses showed a significant influence of the number of professional years, subjectively perceived stress, pressure to succeed, and social isolation. The results suggest that the hormonal stress burden of emergency physicians is in a complex relationship with perceived strain.

Influence of Work-Related and Personal Characteristics on the Burnout Risk among Full- and Part-Time Teachers.

Teachers are at increased risk of stress-related illnesses and burnout symptoms. Thus, a cross-sectional study involving 6109 full-time and 5905 part-time teachers at upper-level secondary schools examined the influence of presumed work-related and personal characteristics on burnout risk between January and April 2018. Burnout was recorded using the Maslach Burnout Inventory—General Survey (MBI-GS). Work-related characteristics were weekly working hours and work stress, operationalized with the effort-reward imbalance (ERI) model. Overcommitment and the inability to recover were determined as personal characteristics. Multiple linear regression analyses were performed, adjusted for age and gender. Overall, 47% of the teachers reported burnout symptoms and 3% had an indication of burnout. Full-time and part-time teachers did not differ in their risk of burnout. ERI, overcommitment, and inability to recover were identified as predictors of burnout risk (explained variance: 29%), whereby the inability to recover was the strongest predictor. In contrast, weekly working hours, extent of employment, gender and age were not related to the burnout risk. ERI was found in 33%, inability to recover in 36% and overcommitment in 39% of all the teachers studied. In particular, the inability to recover should be taken into account as an early indicator of burnout.

Nucleus Accumbens Medium Spiny Neuron Subtypes Differentially Regulate Stress-Associated Alterations in Sleep Architecture

BackgroundStress is implicated in the pathophysiology of major depression and posttraumatic stress disorder. These conditions share core features, including motivational deficits, heighted anxiety, and sleep dysregulation. Chronic stress produces these same features in rodents, with some individuals being susceptible or resilient, as seen in humans. While stress-induced neuroadaptations within the nucleus accumbens are implicated in susceptibility-related dysregulation of motivational and emotional behaviors, their effects on sleep are unclear. MethodsWe used chemogenetics (DREADDs [designer receptors exclusively activated by designer drugs]) to examine the effects of selective alterations in activity of nucleus accumbens medium spiny neurons expressing dopamine D1 receptors (D1-MSNs) or dopamine D2 receptors (D2-MSNs) on sleep-related end points. Mice were implanted with wireless transmitters enabling continuous collection of data to quantify vigilance states over a 20-day test period. Parallel cohorts were examined in behavioral tests assessing stress susceptibility. ResultsD1- and D2-MSNs play dissociable roles in sleep regulation. Stimulation of inhibitory or excitatory DREADDs expressed in D1-MSNs exclusively affects rapid eye movement sleep, whereas targeting D2-MSNs affects slow wave sleep. The combined effects of D1-MSN inhibition and D2-MSN activation on sleep resemble those of chronic social defeat stress. Alterations in D1-MSN function also affect stress susceptibility in social behavior tests. Elevation of CREB (cAMP response element-binding protein) within D1-MSNs is sufficient to produce stress-like effects on rapid eye movement sleep. ConclusionsIn addition to regulation of motivational and emotional behaviors, the nucleus accumbens also influences sleep, an end point with high translational relevance. These findings provide a neural basis for comorbidity in key features of stress-related illness.

Behavioral Deficits Induced by Somatostatin-Positive GABA Neuron Silencing Are Rescued by Alpha 5 GABA-A Receptor Potentiation.

IntroductionDeficits in somatostatin-positive gamma-aminobutyric acid interneurons (SST+ GABA cells) are commonly reported in human studies of mood and anxiety disorder patients. A causal link between SST+ cell dysfunction and symptom-related behaviors has been proposed based on rodent studies showing that chronic stress, a major risk factor for mood and anxiety disorders, induces a low SST+ GABA cellular phenotype across corticolimbic brain regions; that lowering Sst, SST+ cell, or GABA functions induces depressive-/anxiety-like behaviors (a rodent behavioral construct collectively defined as “behavioral emotionality”); and that disinhibiting SST+ cells has antidepressant-like effects. Recent studies found that compounds preferentially potentiating receptors mediating SST+ cell functions, α5-GABAA receptor positive allosteric modulators (α5-PAMs), achieved antidepressant-like effects. Together, the evidence suggests that SST+ cells regulate mood and cognitive functions that are disrupted in mood disorders and that rescuing SST+ cell function via α5-PAM may represent a targeted therapeutic strategy.MethodsWe developed a mouse model allowing chemogenetic manipulation of brain-wide SST+ cells and employed behavioral characterization 30 minutes after repeated acute silencing to identify contributions to symptom-related behaviors. We then assessed whether an α5-PAM, GL-II-73, could rescue behavioral deficits.ResultsBrain-wide SST+ cell silencing induced features of stress-related illnesses, including elevated neuronal activity and plasma corticosterone levels, increased anxiety- and anhedonia-like behaviors, and impaired short-term memory. GL-II-73 led to antidepressant- and anxiolytic-like improvements among behavioral deficits induced by brain-wide SST+ cell silencing.ConclusionOur data validate SST+ cells as regulators of mood and cognitive functions and demonstrate that bypassing low SST+ cell function via α5-PAM represents a targeted therapeutic strategy.

Теоретические аспекты изучения факторов, влияющих на организацию рабочего и личного времени

Work and life balance (WLB) has gained noticeable attention amid the pandemic. Even before the outbreak of COVID-19, the increasing pace of life encouraged the investigation of individual and organisational aspects of WLB. Physically and mentally healthy people help society develop and grow. Health issues caused by work and life imbalance lead to dissatisfaction with both work and life, which, in turn, leads to higher stress and stress-related illnesses, for instance, burnout. From the organisational point of view, WLB is a factor in analysing the efficiency of an enterprise. The consequences of a work-life imbalance are intentional or unintentional absence, high employee turnover, low productivity, higher insurance costs, low job satisfaction, and others. WLB has been examined recently as part of employer branding since a shortage of labour prompts organisations to look for strategies to attract and retain employees. In this paper, content analysis is carried out to provide a theoretical framework for WLB and job satisfaction issues. Special attention is paid to the literature on WLB factors affecting the organisation and the individual. It is concluded that critical factors include both individual and organisational ones. Among them are job involvement, tenure, workload and scheduling, organisational culture (leadership, recreational opportunities, flexibility, supervisor support, autonomy, boundary management, alternative working methods etc.), occupational stress, and salary. These factors differ in their significance, particularly when viewed across several fields.

The Interplay of Nicotine and Social Stress Mediate Dopaminergic Neuron Firing in the Ventral Tegmental Area - Nucleus Accumbens Pathway, Contributing to Stress andDepressive Mood Disorder

Nicotine use and social stress have a complex interplay, which has been shown to be mediated by cholinergic neurons in the ventral tegmental area (VTA). Social stress is often comorbid with nicotine consumption, and the presence of either stress or nicotine use significantly increasesthe riskof developing the other. In fact, it has been shown in mice that nicotine injection is sufficient to increase susceptibility to social defeat, a reliable model for stress and anxiety-like behavior. Stressful events can molecularly remodel cholinergic synapses, inducing the production of more cholinergic transporters and increasing the number of nicotinic receptor binding sites. One way stress and nicotine remodel cholinergic synapses are through long-term potentiation (LTP) in cholinergic pathways in the VTA, enhancing the experience of stress and the effects of addiction. Despite both primarily acting on the alpha7subtype nicotine receptor, nicotine and stress induce LTP in vastly different ways: nicotine acts quickly via ligand-gated ion channels while stress activates a slower hormonal-induced G-protein coupled receptor pathway. These findings suggest that dopaminergic VTA neurons may be a useful therapeutic target for depression, anxiety, and other stress-related disorders. Deep brain stimulation has preliminarily shown to be a potential therapeutic treatment for untreatable depression, especially when it targets the medial forebrain bundle within the VTA-NAc pathway. Sleep patterns are also partially regulated by dopaminergic VTA neurons, and sleep deficits may contribute to social stress and other depressive symptoms. The role of nicotine dependence in stress-related mental illnesses is especially important to consider given the recent increase in adolescent nicotine use with the advent of vaping. Adolescents already have an increased risk for developing mental illnesses, and it is important that young people are made aware of the potential psychological harms of nicotine use.

Social distancing during the COVID-19 pandemic as a predictor of daily psychological, social, and health-related outcomes

In the context of the COVID-19 pandemic, striking public health measures have been implemented to encourage physical distancing in order to slow the spread of disease. However, the impact of these measures on health and wellbeing is not well understood. In the current study a daily diary methodology was used to investigate the effects of social isolation due to the COVID-19 pandemic on a variety of outcomes with 230 undergraduate students. Participants completed an online diary for 3 days, reporting on daily social distancing behaviors, psychological wellbeing/resources, social/interpersonal connection with others, health behaviors, and health outcomes. Overall, daily social distancing (close adherence to social distancing guidelines) was associated with decreases in psychological wellbeing/resources, less social/interpersonal connection with others (including technology-mediated communication), fewer positive health behaviors, and increased reports of stress-related physical illness symptoms. Discussion centers on implications of these findings as well as the importance of identifying ways to mitigate the effects of these necessary but costly measures on health and wellbeing.

Stress assessment by psychophysiological monitoring in daily life

Stress is a natural phenomenon designed to serve as the body's natural survival reaction to real or perceived threats. It is a complex and multifaceted function and its purpose is to allow organisms to adapt quickly to a potentially dangerous situation, promoting an individual's likelihood of survival. Stress levels peak markedly in a 'fight or flight' incident, then reduce again after danger has passed. Stress is designed to work in an acute situation, but when the stress becomes chronic – as is often the case in many modern lifestyles – the body remains constantly on high alert, potentially causing a number of stress-related symptoms. While the exact mechanisms behind it are not clearly understood, stress is recognised as having a major impact on overall human health and wellbeing and, indeed, may directly or indirectly lead to illnesses such as organic or functional disorders, cancer and mental health conditions. Mental health issues and stress-related diseases are becoming ever-more prevalent as modern lifestyles become more pressured, particularly within sub-populations such as those who work in hospitals and in industry. However, the general population is also becoming increasingly affected by stress. Professor Kenji Kanbara, from the Department of Clinical Psychology, Faculty of Medicine at Kagawa University in Japan, is a medical doctor who has an extensive experience in understanding more about stress-related illnesses. 'Psychosomatic processes are subconsciously progressive, and the health threat is significant for that reason,' he highlights. Thus, it is important to be able to recognise and deal with increased stress levels to forestall further health issues.

Physiological and psychological effects of rapid relaxation devices using sensorial immersion: a pilot study

In developed societies, the number of people diagnosed with chronic stress-related illnesses has risen rapidly in recent years. To meet the increasing demand for relaxation and well-being, several companies have developed relaxation installations to be used within business premises or in public locations. The effects of such devices on physiological and psychological parameters have not been scientifically tested yet. This pilot study (N=40) evaluates the variations of 4 physiological and 11 psychological parameters on four different groups, three of them using a different rapid (15 minute) sensorial immersion relaxation devices and a control group using no device. The objective of the study was to identify the psychological and psychological parameters of interest and to study the effects of the devices on these parameters. Physiological parameters measured included heart rate, blood pressure, SpO2 and posture. Psychological parameters included an anxiety survey and four numerical scales to evaluate well-being, energy gain, and subjective muscular and nervous relaxation. We also used cognitive tests and verbatim reports. We identified significant physiological and psychological parameters that can be of use for evaluating rapid relaxation devices (particularly mean blood pressure, posture, subjective muscular and nervous relaxation and some of the cognitive test results). Interestingly, the parameters variations differed between groups. This study paves the way for further analysis of relaxation devices and suggests that rapid sensorial immersion relaxation devices can be of use in stressful environments. Each device could particularly help specific users, depending upon their needs.

English

BACKGROUND Autism is one of the most demanding types of disorders in terms of caregiver’s intervention. A significant amount of distress is always associated with a long term, pervasive intervention and attention given by the care giver. The above scenario leads to depression, adjustment disorder along with suicidal tendencies among the care givers leading to poor prognosis of the disease progress in children and emergence of stress related mental illness in the care givers. Pro-active assessment, diagnosis and management of the above among the care givers might be beneficial for both the child and the care giver along with other family members. METHODS This study was conducted in the special schools of Kancheepuram from December 2019 to February 2020. The cross-sectional study aimed to assess caregiver burden and the variations of burden with varying social and language development in parents of children with ASD (Autism Spectrum Disorder). A total of 60 parents whose children were diagnosed to have Autism Spectrum Disorders were assessed to scale the caregiver burden using Burden Assessment Schedule, and semi structured socio-demographic questionnaire. RESULTS Majority of the caregivers showed an impact on multiple areas of life. 59 % of the caregivers showed significant impact on wellbeing with 84 % feeling depressed and anxious. Lack of appreciation for care was seen in 85 % of the caregivers. Relationship with others was very much impacted in about 14 % of the caregivers. Perceived severity of illness was impacted in 53 % population. CONCLUSIONS Bringing up a child with an autism spectrum disorder is a significant chronic stressor sufficient to disrupt various areas of an adult life and also to cause mental illnesses. Early recognition and management of burden is of immense value in the wellbeing of the caregiver, more importantly in the prognosis of the child’s disorder. KEYWORDS Autism Spectrum Disorder, Caregiver Burden Assessment, Caregiver Burnout

Sport Karate and the Pursuit of Wellness: A Participant Observation Study of a dojo in Scotland.

Health problems in society are numerous, not least stress and stress-related illness. Physical activities, including martial arts, are increasingly viewed as a means of managing such risks to health. While there are forms of karate that have a philosophical and meditative character that is related to spiritual wellness, karate as a competitive sport is less likely to be thought of in this light. The purpose of this paper is to present through a participant observation study the representations that karateka of the dojo, make of sportive karate as a resource to achieve wellness. Drawing on an eight months' immersion in the dojo, we identify five themes that express these karateka's views of sport karate and wellness, the importance of fitness, beauty in punches and kicks, how to embrace fear, the aggressive attitude as a posture in life, and the superiority given by control. The findings lead us to reflect on the need for further research to see if they are repeated in other martial arts, and if many more groups find wellness as a primary motivation for their participation.

Lack of FKBP51 Shapes Brain Structure and Connectivity in Male Mice.

Stress exposure as well as psychiatric disorders are often associated with abnormalities in brain structure or connectivity. The co-chaperone FK506-binding protein 51 (FKBP51) is a regulator of the stress system and is associated with a risk to develop stress-related mental illnesses. To assess the effect of a general FKBP51 knockout on brain structure and connectivity in male mice. Animal study. Two cohorts of FKBP51 knockout (51KO) and wildtype (WT) mice. The first cohort was comprised of n = 18 WT and n = 17 51KOs; second cohort n = 10 WT and n = 9 51KOs. 9.4T/3D gradient echo (VBM), DTI-EPI (DTI). Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI). For VBM, all procedures were executed in SPM12. DTI: FMRIB Software Library (FSL) Tract Based Statistics (TBSS) were integrated within DTI-TK, allowing the creation of a mean FA skeleton. A voxelwise statistical analysis was applied between WT and 51KO mice. Volumetric differences were collected at a threshold of P < 0.005, and only clusters surviving a familywise error correction on the cluster level (pFWE, cluster <0.05) were further considered. VBM data were analyzed using a two-sample t-test. The Threshold Free Cluster Enhancement (TFCE) method was used to derive uncorrected-P statistical results at a P-level of 0.01. The structural analysis revealed two clusters of significantly larger volumes in the hypothalamus, periaqueductal gray, and dorsal raphe region of WT animals. DTI measurements, however, demonstrated statistically higher fractional anisotropy (FA) values for 51KO animals in locations including the anterior commissure, fornix, and posterior commissure/superior colliculus commissure region. This study used in vivo structural MRI and DTI to demonstrate that a lack of FKBP51 leads to alterations in brain architecture and connectivity in male mice. These findings are of particular translational relevance for our understanding of the neuroanatomy underlying the interaction of FKBP5 genetic status, stress susceptibility, and psychiatric disorders. 1 TECHNICAL EFFICACY STAGE: 1.

Effectiveness of a Smartphone App (BioBase) for Reducing Anxiety and Increasing Mental Well-Being: Pilot Feasibility and Acceptability Study.

BackgroundThe prevalence of workplace-related stress and anxiety is high, resulting in stress-related physical and mental illness. Digital self-guided interventions aimed at key areas of workplace design may be able to provide remote anxiolytic effects.ObjectiveThe aim of this feasibility study is to assess changes in anxiety and mental well-being after use of the BioBase programme, a mobile phone platform for psycho-educational modules, tools, and real-time feedback of physiological data.MethodsA 4-week observational study was carried out in 55 healthy adults who were screened for stress with the Depression Anxiety Stress Scale (DASS) Stress subscale. Participants completed anxiety (6-item State-Trait Anxiety Inventory [STAI]) and mental well-being (Warwick-Edinburgh Mental Well-being Scale [WEMWBS]) questionnaires at baseline and at 4 weeks. Feedback questionnaires were administered after 4 weeks.ResultsAfter 4 weeks of using the programme and controlling for any effect of being paid to take part in the study, STAI significantly decreased (baseline mean 45.52 [SD 13.2]; 4-week mean 39.82 [SD 11.2]; t54=–3.51; P<.001; CI –8.88 to –2.52; Cohen d=0.96) and WEMWBS significantly increased (baseline mean 48.12 [SD 6.4]; 4-week mean 50.4 [SD 6.9]; t53=2.41; P=.019; CI 0.44-4.23; Cohen d=0.66). Further, higher baseline stress was significantly associated with a greater decrease in STAI (t53=–3.41; P=.001; CI –8.10 to –2.10; R2=0.180) and a greater increase in WEMWBS (t52=2.41; P=.019; CI 0.38-4.11, R2=0.101). On feedback, participants found the programme easy to use/navigate, with the content being acceptable and relevant to workplace-related stressors; 70% (21/30) of participants would recommend the programme to a friend.ConclusionsThe BioBase programme is a potentially effective intervention in decreasing anxiety and increasing mental well-being, with larger changes in those with higher baseline levels of stress.

Maternal stress programs accelerated aging of the basal ganglia motor system in offspring

Early-life stress involved in the programming of stress-related illnesses can have a toxic influence on the functioning of the nigrostriatal motor system during aging. We examined the effects of perinatal stress (PRS) on the neurochemical, electrophysiological, histological, neuroimaging, and behavioral correlates of striatal motor function in adult (4 months of age) and old (21 months of age) male rats. Adult PRS offspring rats showed reduced dopamine (DA) release in the striatum associated with reductions in tyrosine hydroxylase-positive (TH+) cells and DA transporter (DAT) levels, with no loss of striatal dopaminergic terminals as assessed by positron emission tomography analysis with fluorine-18-l-dihydroxyphenylalanine. Striatal levels of DA and its metabolites were increased in PRS rats. In contrast, D2 DA receptor signaling was reduced and A2A adenosine receptor signaling was increased in the striatum of adult PRS rats. This indicated enhanced activity of the indirect pathway of the basal ganglia motor circuit. Adult PRS rats also showed poorer performance in the grip strength test and motor learning tasks. The aged PRS rats also showed a persistent reduction in striatal DA release and defective motor skills in the pasta matrix and ladder rung walking tests. In addition, the old rats showed large increases in the levels of SNAP-25 and synaptophysin, which are synaptic vesicle-related proteins in the striatum, and in the PRS group only, reductions in Syntaxin-1 and Rab3a protein levels were observed. Our findings indicated that the age-dependent threshold for motor dysfunction was lowered in PRS rats. This area of research is underdeveloped, and our study suggests that early-life stress can contribute to an increased understanding of how aging diseases are programmed in early-life.

Genome-wide translational profiling of amygdala Crh-expressing neurons reveals role for CREB in fear extinction learning

Fear and extinction learning are adaptive processes caused by molecular changes in specific neural circuits. Neurons expressing the corticotropin-releasing hormone gene (Crh) in central amygdala (CeA) are implicated in threat regulation, yet little is known of cell type-specific gene pathways mediating adaptive learning. We translationally profiled the transcriptome of CeA Crh-expressing cells (Crh neurons) after fear conditioning or extinction in mice using translating ribosome affinity purification (TRAP) and RNAseq. Differential gene expression and co-expression network analyses identified diverse networks activated or inhibited by fear vs extinction. Upstream regulator analysis demonstrated that extinction associates with reduced CREB expression, and viral vector-induced increased CREB expression in Crh neurons increased fear expression and inhibited extinction. These findings suggest that CREB, within CeA Crh neurons, may function as a molecular switch that regulates expression of fear and its extinction. Cell-type specific translational analyses may suggest targets useful for understanding and treating stress-related psychiatric illness.