Stress-related Disorders Research Articles

Female students’ personality and stress response to an academic examination

ABSTRACT Background Women are vulnerable to stress-related disorders. Examinations are a source of stress, triggering emotional, cognitive, and hormonal responses. We examined women’s psychological and hormonal stress responses and academic performance according to personality during a real-life examination. Methods Female students (N = 66) were divided into two groups based on hierarchical cluster analysis: one cluster characterized by high neuroticism and moderate extraversion (HN-ME; n = 42) and the other by low neuroticism and high extraversion (LN-HE; n = 24). Academic performance, perceived stress, and emotional dysregulation were analyzed. State anxiety, affect, and cortisol release were measured before and on the examination day. Results The HN-ME cluster was high in perceived stress, emotional dysregulation, and negative affect. This cluster also had higher state anxiety levels two days before and shortly after the examination compared to the LN-HE cluster. Students’ cortisol levels were higher on the examination day, and there was a marginal significance of the Cluster factor in the cortisol release regardless of the day of measurement. Conclusions Women with high neuroticism and moderate extraversion may be more vulnerable to psychological stress in academic settings but similar to other women in their cortisol response.

Anxiety disorders in the structure of stress-related disorders in forced immigrants

Anxiety disorders in the structure of stress-related disorders in forced immigrants

Overall and Cervical Cancer Survival in Patients With and Without Mental Disorders

Individuals with a mental disorder experience substantial health disparity and are less likely to participate in cervical screening and human papillomavirus vaccination. Additionally, this population may benefit less from tertiary cancer prevention. To compare clinical characteristics and survival patterns between patients with cervical cancer with and without a preexisting diagnosis of a mental disorder at the time of cervical cancer diagnosis. This cohort study obtained data from Swedish population-based (Swedish Cancer Register, Swedish Cause of Death Register, Swedish Total Population Register, Swedish Patient Register, and Swedish Longitudinal Integration Database for Health Insurance and Labor Market Studies) and quality registries (Swedish Quality Register of Gynecologic Cancer and Swedish National Cervical Screening Register) on patients with cervical cancer. Patients who were included in the analysis were identified using the Swedish Cancer Register and were diagnosed with cervical cancer between 1978 and 2018. The Swedish Patient Register was used to identify patients with mental disorders using codes from the International Classification of Diseases, Eighth Revision and Ninth Revision and the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. Because data on clinical characteristics at the time of cancer diagnosis were available for only for part of the study population, 2 patient groups were created: those with cervical cancer diagnosed from 2002 to 2016 and all patients diagnosed with cervical cancer (1978-2018). Data analyses were carried out between March and September 2022. Clinical diagnoses of a mental disorder, including substance abuse, psychotic disorders, depression, anxiety, stress-related disorders, attention-deficit/hyperactivity disorder, autism, and intellectual disability, prior to cervical cancer. Death due to any cause or due to cervical cancer as ascertained from the Swedish Cause of Death Register. The sample included 20 177 females (mean [SD] age, 53.4 [17.7] years) diagnosed with cervical cancer from 1978 to 2018. In a subgroup of 6725 females (mean [SD] age, 52.2 [18.0] years) with cervical cancer diagnosed from 2002 to 2016, 893 (13.3%) had a preexisting diagnosis of a mental disorder. Compared with patients with no preexisting mental disorder diagnosis, those with a preexisting mental disorder had a higher risk of death due to any cause (hazard ratio [HR], 1.32; 95% CI, 1.17-1.48) and due to cervical cancer (HR, 1.23; 95% CI, 1.07-1.42). These risks were lower after adjustment for cancer characteristics at the time of cancer diagnosis (death due to any cause: HR, 1.19 [95% CI, 1.06-1.34] and death due to cervical cancer: HR, 1.12 [95% CI, 0.97-1.30]). Risk of death was higher for patients with substance abuse, psychotic disorders, or mental disorders requiring inpatient care. Among patients with cervical cancer diagnosed from 1978 to 2018, the estimated 5-year survival improved continuously during the study period regardless of preexisting diagnosis of a mental disorder status. For example, in 2018, the estimated 5-year overall survival proportion was 0.66 (95% CI, 0.60-0.71) and 0.74 (95% CI, 0.72-0.76) for patients with and without a preexisting diagnosis of a mental disorder, respectively. Findings of this cohort study suggest that patients with cervical cancer and a preexisting diagnosis of a mental disorder have worse overall and cervical cancer-specific survival than patients without a preexisting mental disorder diagnosis, which may be partly attributable to cancer and sociodemographic characteristics at diagnosis. Hence, individuals with mental disorders deserve special attention in the tertiary prevention of cervical cancer.

Reduced length of nodes of Ranvier and altered proteoglycan immunoreactivity in prefrontal white matter in major depressive disorder and chronically stressed rats

Major depressive disorder (MDD) and chronic unpredictable stress (CUS) in animals feature comparable cellular and molecular disturbances that involve neurons and glial cells in gray and white matter (WM) in prefrontal brain areas. These same areas demonstrate disturbed connectivity with other brain regions in MDD and stress-related disorders. Functional connectivity ultimately depends on signal propagation along WM myelinated axons, and thus on the integrity of nodes of Ranvier (NRs) and their environment. Various glia-derived proteoglycans interact with NR axonal proteins to sustain NR function. It is unclear whether NR length and the content of associated proteoglycans is altered in prefrontal cortex (PFC) WM of human subjects with MDD and in experimentally stressed animals. The length of WM NRs in histological sections from the PFC of 10 controls and 10 MDD subjects, and from the PFC of control and CUS rats was measured. In addition, in WM of the same brain region, five proteoglycans, tenascin-R and NR protein neurofascin were immunostained or their levels measured with western blots. Analysis of covariance and t-tests were used for group comparisons. There was dramatic reduction of NR length in PFC WM in both MDD and CUS rats. Proteoglycan BRAL1 immunostaining was reduced at NRs and in overall WM of MDD subjects, as was versican in overall WM. Phosphacan immunostaining and levels were increased in both in MDD and CUS. Neurofascin immunostaining at NRs and in overall WM was significantly increased in MDD. Reduced length of NRs and increased phosphacan and neurocan in MDD and stressed animals suggest that morphological and proteoglycan changes at NRs in depression may be related to stress exposure and contribute to connectivity alterations. However, differences between MDD and CUS for some NR related markers may point to other mechanisms affecting the structure and function of NRs in MDD.

Previous psychiatric hospitalizations as risk factors for single and multiple future alcohol-related hospitalizations in patients with alcohol use disorders.

People with alcohol use disorder (AUD) often have co-occurring psychiatric conditions. The association between psychiatric conditions and AUD relapse has not yet been fully explored. This study aimed to quantify different psychiatric comorbidities as risk factors for first and multiple AUD rehospitalizations in patients already hospitalized once for AUD. We used a nation-wide routine health-care database in Scotland, UK, between 2010 and 2019. Individuals with a first hospitalization for AUD (codes F10.0-9 in the ICD-10 codes) were checked for previous hospitalizations where the main or co-occurring cause was a psychiatric condition (any other F0-F99 code in ICD-10). The final cohort included 23 529 patients, 18 620 of whom did not have a history of any other psychiatric comorbidity. First, individuals with a history of any previous psychiatric hospitalization were grouped and compared with those without on the basis of time to AUD rehospitalization. Then, individuals with different histories of psychiatric hospitalization were compared with each other. Cox and Prentice, Williams and Peterson gap-time models were used for single and multiple AUD rehospitalizations, respectively. The AUD rehospitalization rate in individuals with a previous psychiatric hospitalization was 8% higher compared with those without [hazard ratio (HR) = 1.08, 95% confidence interval (CI) = 1.01-1.14]. The difference in rehospitalization rate reduced following the first rehospitalization (HR at second rehospitalization from first: 0.95, 95% CI = 0.87-1.04 and HR at third rehospitalization from second: 0.94, 95% CI = 0.84-1.07). Mood disorders and neurotic, stress-related and somatoform disorders were associated with a 54% (HR = 1.54, 95% CI = 1.38-1.72) and 39% (HR = 1.39, 95% CI = 1.17-1.66) increase in the risk of a first AUD rehospitalization. Other conditions, such as disorders due to psychoactive substance use or schizophrenia, were associated with decreases in future AUD rehospitalization (HR = 0.89, 95% CI = 0.82-0.97 and HR = 0.82, 95% CI = 0.58-1.16, respectively). Patients with AUD appear to have different rates of AUD rehospitalization based on different co-occurring psychiatric conditions. Addiction-related characteristics may be more relevant risk indicators for multiple AUD readmission than psychiatric comorbidities.

EFFECTIVENESS OF OCCUPATIONAL THERAPY FOR PEOPLE WITH SYMPTOMS OF ANXIETY

The main objective of the empirical study is to establish the effect of the application of occupational therapy on residents living in an institutional environment, who often experience anxiety, distress, social isolation, sadness, which are processes that often lead to a decline in physical and psychological functioning. The high prevalence of these stress-related disorders has impeded the ability of a high number of individuals individuals to participate in regular life activities (Fox et al., 2019). The experimental base of the present research is the Home for Adults with Physical Disabilities “Ilho Voivoda”, Kyustendil, and the research contingent is 44 adults housed in the Home. The recipients of the social service have a wide range of diseases: multiple sclerosis, spina bifida, muscular dystrophy, limb malformations, cerebral palsy, paraplegia, heart attack, stroke, etc. All of them have preserved mental faculties. A test study was conducted with a personality-based questionnaire, created on the basis of the PAI - Personality Assessment Inventory, intended for the study of adults in order to provide information relevant to clinical diagnoses and screening for psychopathology. For the purpose of the present study, items from the PAI were used, which aim to detect the symptoms and phenomenology of anxiety. The Anxiety scale measures traits commonly associated with the experience of anxiety. Item content includes various characteristics of anxiety, including worry, subjective apprehension, and fear of humiliation, as well as the physical signs of tension and stress. The scale is composed of three subscales corresponding to three main modalities of anxiety: Cognitive, Affective and Physiological. The occupational therapy process was designed to move through multiple cycles of problem identification, followed by solution generation, while the main focus remained on occupation and the human factor in the occupational context (Crouch & Alers, 2014). The results after the occupational therapy are indicative of its significant effectiveness. The improved indicators include: the number of residents with anxiety from 41 (93.2%) before occupational therapy was carried out decreased to 21 (47.7%), i.e. by almost 50%. In conclusion, according to the results of the present study, it can be assumed that occupational therapy occupies a leading position in rehabilitation therapies in social institutions. It provides an opportunity to get rid of negative emotions such as anxiety, anger, dissatisfaction, disappointment, insult, hostility.

Evaluation of the Anti-inflammatory, Antimicrobial, Antioxidant, and Cytotoxic Effects of Chitosan Thiocolchicoside-Lauric Acid Nanogel.

The present study explored the anti-inflammatory, antimicrobial, antioxidant, and cytotoxic effects of a combination of chitosan thiocolchicoside and lauric acid (CTLA) nanogel. Materials and methods: A nanogel formulation of thiocolchicoside and lauric acid was developed and tested for potential applications. The antimicrobial activity was assessed using the well diffusion method, while the antioxidant activity was evaluated using the 2,2-diphenyl-1-picryl hydrazyl (DPPH) free radical scavenging assay and hydrogen peroxide (H2O2) antioxidant assay methods. The anti-inflammatory activity was determined through the egg albumin denaturation method, the bovine serum albumin denaturation method, and the membrane stabilization assay. A brine shrimp lethality assay was used to study the cytotoxic effect of the nanogel. We identified significant positive outcomes for the CTLAnanogel. The results showed a percentage of inhibition of 81% at 50μg/mL, which showed the nanogel's significant anti-inflammatory activity by inhibiting bovine serum albumin denaturation. The anti-inflammatory properties of the nanogel were comparable to the standard diclofenac sodium at all tested concentrations. The egg albumin denaturation assay results revealed a percentage inhibition of 76% at 50 μg/mL. In the membrane stabilization assay, a percentage inhibition of86%was obtained at a concentration of 50 μg/mL against 89% for the standard drug. The nanogel exhibited a zone of inhibition of 20 mm against Streptococcus mutans and 22 mm with a dilution of 100 µg/mL of CTLA nanogel against Staphylococcus aureus. The antioxidant activity was studied by using the DPPH method, 50 μg/ml has an 89% inhibition, which was similar to the standard. The inhibitory activity of CTLAnanogel at 50 μg/ml was81.6%in the hydroxyl free radical scavenging assay, which was comparable to the standard drug. At 5 μg/mL concentration of CTLA nanogel, approximately 90% of the nauplii remained alive after 48 hours. The CTLAnanogel showed excellent anti-inflammatory and antioxidant properties suggesting its potential for managing inflammatory conditions and oxidative stress-related disorders.

The Association Between Mental Health, Substance Use Disorder, and Outcomes After Total Joint Arthroplasty

BackgroundPrior studies suggest that distressed patients or those who have poor mental health have inferior postoperative outcomes when compared to nondistressed patients. However, these studies typically do not account for substance use or other comorbidities often found in this population, which can independently contribute to postoperative complications. This study sought to control for these factors and assess if a diagnosis of a mental health condition is directly associated with worse outcomes after total joint arthroplasty. MethodsA retrospective chart review was performed for 3,182 patients who underwent a total hip arthroplasty and 4,430 patients who underwent a total knee arthroplasty. Diagnosis of the mental health disorders included depression, anxiety disorder, adjustment disorder, bipolar disorder, trauma, stressor-related disorder, and schizophrenia or schizoaffective disorder. Multivariable analyses were performed to control for alcohol use, drug use, tobacco use, body mass index, and a comorbidity index. ResultsWhen controlling for body mass index and Charlson comorbidity index, no statistically significant associations were found between a diagnosis of any mental health condition or a specific diagnosis of depression or anxiety, and 90-day readmission, reoperation, or 1 year mortality for patients undergoing total knee arthroplasty or total hip arthroplasty. ConclusionsWhen accounting for confounding factors, there does not appear to be a direct association between diagnosis of any of the psychiatric conditions we studied and outcomes after primary total joint arthroplasty. While prior studies suggest addressing the mental health condition may improve outcomes, this study suggests that preoperative medical optimization and potentially addressing substance use may be more effective strategies.

52 An Evaluation of Satisfaction with Emergency Department Care in Children and Adolescents with Mental Health Concerns

Abstract Background Increasingly, the emergency department (ED) is a vital safety net for children and adolescents with mental health concerns seeking crisis care. Evaluating patient and parent/caregiver experience and satisfaction with care is essential to improve the quality of mental health services provided. Objectives The primary objective was to evaluate total satisfaction with the delivery of ED mental health care in two paediatric EDs in Alberta, Canada (Stollery Children's Hospital and Alberta Children's Hospital). Secondary objectives included exploring aspects of ED mental health care (staff interpersonal skills, confidentiality/privacy, and patient-reported outcomes of care) associations with general satisfaction, patient and ED visit characteristic associations with total satisfaction score, and care experience themes. Design/Methods We enrolled patients <18 years of age presenting with a mental health concern—e.g., anxiety, disruptive behaviour, self-harm, depression, situational crisis—over a 12-month period (February 1, 2020—January 31, 2021). Satisfaction data were collected using the Service Satisfaction Scale, which includes quantitative and qualitative data on aspects of ED mental health care. ED visit (length of stay, mental health and psychiatry consultations, hospital admission) and patient (discharge diagnoses, age, sex) data were collected. We evaluated associations of general satisfaction with ED mental health care using Pearson’s correlation coefficient tests, and associations between total satisfaction score with patient and ED visit characteristics using multivariable regression analyses. Inductive thematic analysis of qualitative feedback identified satisfaction and patient experience themes. Results 646 participants were enrolled with most being Caucasian (71.2%; 460/646) and female (56.3%; 364/646); the median age was 13 years (IQR, 11-15 years). The most common discharge diagnosis was anxiety or stress-related disorders (39.5%; 245/620). Parents/caregivers and adolescents were most satisfied with confidentiality and respect in the ED and least satisfied with how the ED services helped reduce symptoms and/or problems. Greater satisfaction was reported for parents/caregivers whose child received care at Alberta Children’s Hospital (p=0.003). General satisfaction was strongly associated with the perceived amount of help received in the ED (r=0.85). ED visit characteristics associated with total satisfaction score included an evaluation by a mental health team member (p=0.004) and psychiatrist consultation (p=0.05). Written comments demonstrated satisfaction with ED provider attitudes and interpersonal skills and dissatisfaction with access to mental health and addictions care, wait time, and COVID-19. Conclusion The results reflect the need to improve the satisfaction with ED mental health care delivery, with a particular focus on enhancing access to care by appropriate mental health providers.

Does employer involvement in primary health care enhance return to work for patients with stress-related mental disorders? a cluster randomized controlled trial

BackgroundStress-related disorders have become a major challenge for society and are associated with rising levels of sick leave. The provision of support to facilitate the return to work (RTW) for this patient group is of great importance. The aim of the present study was to evaluate whether a new systematic procedure with collaboration between general practitioners (GPs), rehabilitation coordinators (RCs) and employers could reduce sick leave days for this patient group.MethodEmployed patients with stress-related diagnoses seeking care at primary health care centres (PHCCs) were included in either the intervention group (n = 54), following the systematic intervention procedure, or the control group (n = 58), receiving treatment as usual (TAU). The intervention included a) a training day for participant GPs and RCs, b) a standardised procedure for GPs and RCs to follow after training, c) the opportunity to receive clinical advice from specialist physicians in the research group. Outcome measures for RTW were sick leave days.ResultsThe median number of registered gross sick leave days was lower for the control group at six, 12 and 24 months after inclusion, but the difference was not statistically significant. The control group had significantly fewer net sick leave days at three months (p = 0.03) at six months (p = 0.00) and at 12-months follow-up (p = 0.01). At 24 months, this difference was no longer significant.ConclusionsThe PRIMA intervention, which applied a standardized procedure for employer involvement in the rehabilitation process for patients with stress-related disorders, actually increased time to RTW compared to TAU. However, at 24 months, the benefit of TAU could no longer be confirmed. The study was registered on 16/01/2017 (ClinicalTrials.gov, NCT03022760).

Long-term social isolation stress exacerbates sex-specific neurodegeneration markers in a natural model of Alzheimer's disease.

Social interactions have a significant impact on health in humans and animal models. Social isolation initiates a cascade of stress-related physiological disorders and stands as a significant risk factor for a wide spectrum of morbidity and mortality. Indeed, social isolation stress (SIS) is indicative of cognitive decline and risk to neurodegenerative conditions, including Alzheimer's disease (AD). This study aimed to evaluate the impact of chronic, long-term SIS on the propensity to develop hallmarks of AD in young degus (Octodon degus), a long-lived animal model that mimics sporadic AD naturally. We examined inflammatory factors, bioenergetic status, reactive oxygen species (ROS), oxidative stress, antioxidants, abnormal proteins, tau protein, and amyloid-β (Aβ) levels in the hippocampus of female and male degus that were socially isolated from post-natal and post-weaning until adulthood. Additionally, we explored the effect of re-socialization following chronic isolation on these protein profiles. Our results showed that SIS promotes a pro-inflammatory scenario more severe in males, a response that was partially mitigated by a period of re-socialization. In addition, ATP levels, ROS, and markers of oxidative stress are severely affected in female degus, where a period of re-socialization fails to restore them as it does in males. In females, these effects might be linked to antioxidant enzymes like catalase, which experience a decline across all SIS treatments without recovery during re-socialization. Although in males, a previous enzyme in antioxidant pathway diminishes in all treatments, catalase rebounds during re-socialization. Notably, males have less mature neurons after chronic isolation, whereas phosphorylated tau and all detectable forms of Aβ increased in both sexes, persisting even post re-socialization. Collectively, these findings suggest that long-term SIS may render males more susceptible to inflammatory states, while females are predisposed to oxidative states. In both scenarios, the accumulation of tau and Aβ proteins increase the individual susceptibility to early-onset neurodegenerative conditions such as AD.

Increased hippocampal CREB phosphorylation after retrieval of remote contextual fear memories in Carioca high-conditioned freezing rats

The participation of the hippocampal formation in consolidation and reconsolidation of contextual fear memories has been widely recognized and known to be dependent on the activation of the cAMP response element (CRE) binding protein (CREB) pathway. Recent findings have challenged the prevailing view that over time contextual fear memories migrate to neocortical circuits and no longer require the hippocampus for retrieval of remote fearful memories. It has also recently been found that this brain structure is important for the maintenance and recall of remote fear memories associated with aversive events, a common trait in stress-related disorders such as generalized anxiety disorder (GAD), major depression, and post-traumatic stress disorder. In view of these findings, here we examined the putative role of CREB in the hippocampus of an animal model of GAD during the retrieval of remote contextual fear memories. Specifically, we evaluated CREB phosphorylation in the hippocampus of male Carioca High- and Low-conditioned Freezing rats (CHF and CLF, respectively) upon re-exposure of animals to contextual cues associated to footshocks weeks after fear conditioning. Age-matched male rats from a randomized crossbreeding population served as controls (CTL). Adrenal catecholamine levels were also measured as a biological marker of stress response. Seven weeks after contextual fear conditioning, half of the sample of CHF (n = 9), CLF (n = 10) and CTL (n = 10) rats were randomly assigned to return to the same context chamber where footshocks were previously administrated (Context condition), while the remaining animals were individually placed in standard housing cages (Control condition). Western blot results indicated that pCREB levels were significantly increased in the hippocampus of CHF rats for both Context and Control conditions when compared to the other experimental groups. CHF rats in the Context condition also exhibited significant more freezing than that observed for both CLF and CTL rats. Lastly, CHF animals in the Context condition displayed significantly higher adrenal catecholamine levels than those in the Control condition, whereas no differences in catecholamine levels were observed between Context and Control conditions for CLF and CTL rats. These findings are discussed from a perspective in which the hippocampus plays a role in the maintenance and recall of remote contextual fear memories via the CREB pathway.

Telehealth and In-Person Behavioral Health Services in Rural Communities Before and During the COVID-19 Pandemic: Multisite Prospective Cohort Study.

The COVID-19 pandemic triggered widespread adjustments across the US health care system. Telehealth use showed a substantial increase in mental health conditions and services due to acute public health emergency (PHE) behavioral health needs on top of long-standing gaps in access to behavioral health services. How health systems that were already providing behavioral telehealth services adjusted services and staffing during this period has not been well documented, particularly in rural areas with chronic shortages of behavioral health providers and services. This study investigates patient and treatment characteristic changes from before the COVID-19 PHE to during the PHE within both telehealth and in-person behavioral health services provided in 95 rural communities across the United States. We used a nonrandomized, prospective, multisite research design involving 2 active treatment groups. The telehealth cohort included all patients who initiated telehealth treatment regimens during the data collection period. A comparison group included a cohort of patients who initiated in-person treatment regimen. Patient enrollment occurred on a rolling basis, and data collection was extended for 3 months after treatment initiation for each patient. Chi-square tests compared changes from pre-PHE to PHE time periods within telehealth and in-person treatment cohorts. The dependent measures included patient diagnosis, clinicians providing treatment services, and type of treatment services provided at each encounter. The 4780 patients in the telehealth cohort and the 6457 patients in the in-person cohort had an average of 3.5 encounters during the 3-month follow-up period. The encounters involving anxiety, dissociative, and stress-related disorders in the telehealth cohort increased from 30% (698/2352) in the pre-PHE period to 35% (4632/12,853) in the PHE period (P<.001), and encounters involving substance use disorders in the in-person cohort increased from 11% (468/4249) in the pre-PHE period to 18% (3048/17,047) in the PHE period (P<.001). The encounters involving treatment service codes for alcohol, drug, and medication-assisted therapy in the telehealth cohort increased from 1% (22/2352) in the pre-PHE period to 11% (1470/13,387) in the PHE period (P<.001); likewise, encounters for this type of service in the in-person cohort increased from 0% (0/4249) in the pre-PHE period to 16% (2687/17,047) in the PHE period (P<.001). From the pre-PHE to the PHE period, encounters involving 60-minute psychotherapy in the telehealth cohort increased from 8% (190/2352) to 14% (1802/13,387; P<.001), while encounters involving group therapy in the in-person cohort decreased from 12% (502/4249) to 4% (739/17,047; P<.001). The COVID-19 pandemic challenged health service providers, and they adjusted the way both telehealth and in-person behavioral therapy services were delivered. Looking forward, future research is needed to explicate the interaction of patient, provider, setting, and intervention factors that influenced the patterns observed as a result of the COVID-19 pandemic.

Involvement of brain-derived neurotrophic factor signaling in the pathogenesis of stress-related brain diseases.

Neurotrophins including brain-derived neurotrophic factor, BDNF, have critical roles in neuronal differentiation, cell survival, and synaptic function in the peripheral and central nervous system. It is well known that a variety of intracellular signaling stimulated by TrkB, a high-affinity receptor for BDNF, is involved in the physiological and pathological neuronal aspects via affecting cell viability, synaptic function, neurogenesis, and cognitive function. As expected, an alteration of the BDNF/TrkB system is suspected to be one of the molecular mechanisms underlying cognitive decline in cognitive diseases and mental disorders. Recent evidence has also highlighted a possible link between the alteration of TrkB signaling and chronic stress. Furthermore, it has been demonstrated that downregulation of the BDNF/TrkB system and chronic stress have a role in the pathogenesis of Alzheimer's disease (AD) and mental disorders. In this review, we introduce current evidence showing a close relationship between the BDNF/TrkB system and the development of cognition impairment in stress-related disorders, and the possible contribution of the upregulation of the BDNF/TrkB system in a therapeutic approach against these brain diseases.

Transcutaneous vagal nerve stimulation modulates stress-induced plasma ghrelin levels: A double-blind, randomized, sham-controlled trial

BackgroundTranscutaneous cervical vagus nerve stimulation (tcVNS) has emerged as a potential treatment strategy for patients with stress-related psychiatric disorders. Ghrelin is a hormone that has been postulated to be a biomarker of stress. While the mechanisms of action of tcVNS are unclear, we hypothesized that tcVNS reduces the levels of ghrelin in response to stress. MethodsUsing a randomized double-blind approach, we studied the effects of tcVNS on ghrelin levels in individuals with a history of exposure to traumatic stress. Participants received either sham (n = 29) or active tcVNS (n = 26) after exposure to acute personalized traumatic script stress and mental stress challenges (public speech, mental arithmetic) over a three day period. ResultsThere were no significant differences in the levels of ghrelin between the tcVNS and sham stimulation groups at either baseline or in the absence of trauma scripts. However, tcVNS in conjunction with personalized traumatic scripts resulted in lower ghrelin levels compared to the sham stimulation group (265.2 ± 143.6 pg/ml vs 478.7 ± 349.2 pg/ml, P = 0.01). Additionally, after completing the public speaking and mental arithmetic tests, ghrelin levels were found to be lower in the group receiving tcVNS compared to the sham group (293.3 ± 102.4 pg/ml vs 540.3 ± 203.9 pg/ml, P = 0.009). LimitationsTiming of ghrelin measurements, and stimulation of only left vagus nerve. ConclusiontcVNS decreases ghrelin levels in response to various stressful stimuli. These findings are consistent with a growing literature that tcVNS modulates hormonal and autonomic responses to stress.

A Survey on Factors Influencing the Work-Family-Health Balance of an Interventional Radiologist.

Aim: Burnout and stress-related health disorders are on the rise among physicians. The aim of this study is to report the results of a survey on factors affecting the work-life balance of interventional radiologists (IR). Material: The survey consisted of 30 questions focusing on work, family, and personal health. The questionnaire addressed knowledge, attitude, and practice. This online survey was sent to IRs across the globe and the responses were analyzed by three IRs (SH, SNK, SK). Results: On univariate analysis, the major risk factors for burnout were presence of weekend duties ( n = 91, 98.9%, p = 0.02), absence of support group at workplace ( n = 36, 39.1%, p = 0.005), having tough time with administration ( n = 61, 66.3%, p = 0.001), not able to spend quality time on family ( n = 30, 32.6%, p = 0.035), and inability to find time to do things that one enjoys ( n = 53, 57.6%, p = 0.0002). However, multivariate analysis revealed that those having tough time with administration (odds ratio = 2.77 [95% confidence interval [CI]: 1.12-6.48], p = 0.02) and those who could not find time to do things one enjoys (odds ratio = 4.79 [95% CI: 1.42-16.1], p = 0.01) were only statistically significant. Conclusion: Burnout is common among IRs and is considered a significant issue that needs to be addressed. Teamwork, a support structure for major events, healthy lifestyle, and dedicated time for family may combat the burnout.

Accelerated Fear Extinction by Regular Light-Intensity Exercise: A Possible Role of Hippocampal BDNF-TrkB Signaling.

Growing concern exists worldwide about stress-related mental disorders, such as posttraumatic stress disorder (PTSD), often linked to hippocampal dysfunctions. Recognizing this connection, regular light-intensity exercise (LIE)-such as yoga, walking, or slow jogging-may offer a solution. Easily accessible even to vulnerable individuals, LIE has been found to enhance hippocampus-based cognitive functions through the stimulation of neurotrophic factors like brain-derived neurotrophic factor (BDNF). A prior study that demonstrated BDNF's role in extinguishing original fear memory further leads us to propose that a consistent LIE training might drive fear extinction learning, offering potential therapeutic benefits through BDNF signaling. Eleven-week-old Wistar rats underwent 4 wk of training under conditions of sedentary, LIE, or moderate-intensity exercise (MOE) after contextual or auditory fear conditioning. Subsequently, fear extinction tests were performed. We then administered intraperitoneal (i.p.) ANA-12, a selective antagonist of tropomyosin receptor kinase B (TrkB), or a vehicle to explore the role of BDNF signaling in exercise-induced fear extinction among the LIE rats. Following the regular exercise training, further fear extinction tests were conducted, and hippocampal protein analysis was performed using Western blotting. Both LIE and MOE over 4 wk accelerated hippocampus-associated contextual fear extinction compared with sedentary. In addition, 4 wk of LIE with i.p. administered vehicle increased hippocampal BDNF and TrkB protein levels. In contrast, i.p. ANA-12 administration fully blocked the LIE-enhanced protein levels and its effect on contextual fear extinction. Our findings reveal that LIE regimen promotes fear extinction learning, at least partially tied to hippocampal BDNF-TrkB signaling. This suggests that even regular light exercise could alleviate the excessive fear response in anxiety disorders and PTSD, providing hope for those affected.

New progress in an old debate? Applying the DSM-5 criteria to assess traumatic events and stressor-related disorders in cancer survivors.

The rather broad definition of medical trauma within DSM-IV has contributed to long-lasting debates on the applicability of Posttraumatic Stress Disorder (PTSD) in oncological patients and its differentiation from Adjustment Disorder (AjD) which results from non-traumatic critical life events. The DSM-5 criteria have introduced a narrower definition of medical traumatization. However, studies on updated prevalence rates in cancer patients are missing. Within a cross-sectional study, we assessed hematological cancer survivors using the Structured Clinical Interview for DSM-5. We investigated (i) the frequency and type of cancer-related stressors, (ii) the proportion of stressors qualifying as traumatic according to DSM-5 (i.e., an event of sudden and catastrophic character) and (iii) the prevalence of PTSD, AjD and cancer-related PTSD according to DSM-5. 291 patients participated (response rate: 58%). Mean age was 54years, 60% were male. 168 patients (59%) reported cancer-related stressors, with the most frequent being cancer diagnosis disclosure (n=58, 27%). Eight percent of reported stressors qualified as traumatic events according to DSM-5. Five (1.8%), 15 (5.3%) and 20 (7.0%) cancer survivors met DSM-5 criteria for current PTSD, lifetime PTSD and AjD, respectively. Among all PTSD cases, three were cancer-related (1.1%). In addition, seven patients (2.5%) metall symptoms for cancer-related PTSD, but not the DSM-5 criterion for medical trauma. Considering receiving the cancer diagnosis as traumatic event, which is debatable according to DSM-5, 38% of stressors qualified as traumatic and six patients (2.1%) met criteria for cancer-related PTSD. DSM-5 criteria enable a clear identification of traumatic events in the context of cancer. This change may inform discussions on the appropriateness of PTSD in cancer patients and facilitates its differentiation from AjD. Larger studies need to validate our findings.

Psilocybin induces acute and persisting alterations in immune status in healthy volunteers: An experimental, placebo-controlled study

Patients characterized by stress-related disorders such as depression display elevated circulating concentrations of pro-inflammatory cytokines and a hyperactive HPA axis. Psychedelics are demonstrating promising results in treatment of such disorders, however the mechanisms of their therapeutic effects are still unknown. To date the evidence of acute and persisting effects of psychedelics on immune functioning, HPA axis activity in response to stress, and associated psychological outcomes is preliminary. To address this, we conducted a placebo-controlled, parallel group design comprising of 60 healthy participants who received either placebo (n = 30) or 0.17 mg/kg psilocybin (n = 30). Blood samples were taken to assess acute and persisting (7 day) changes in immune status. Seven days’ post-administration, participants in each treatment group were further subdivided: 15 underwent a stress induction protocol, and 15 underwent a control protocol. Ultra-high field (7-Tesla) magnetic resonance spectroscopy was used to assess whether acute changes in glutamate or glial activity were associated with changes in immune functioning. Finally, questionnaires assessed persisting self-report changes in mood and social behavior. Psilocybin immediately reduced concentrations of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), while other inflammatory markers (interleukin (IL)- 1β, IL-6, and C-reactive protein (CRP)) remained unchanged. Seven days later, TNF-α concentrations returned to baseline, while IL-6 and CRP concentrations were persistently reduced in the psilocybin group. Changes in the immune profile were related to acute neurometabolic activity as acute reductions in TNF-α were linked to lower concentrations of glutamate in the hippocampus. Additionally, the more of a reduction in IL-6 and CRP seven days after psilocybin, the more persisting positive mood and social effects participants reported. Regarding the stress response, after a psychosocial stressor, psilocybin did not significantly alter the stress response. Results are discussed in regards to the psychological and therapeutic effects of psilocybin demonstrated in ongoing patient trials.

Chronic psychosocial stress triggers microglial-/macrophage-induced inflammatory responses leading to neuronal dysfunction and depressive-related behavior.

Chronic environmental stress and traumatic social experiences induce maladaptive behavioral changes and is a risk factor for major depressive disorder (MDD) and various anxiety-related psychiatric disorders. Clinical studies and animal models of chronic stress have reported that symptom severity is correlated with innate immune responses and upregulation of neuroinflammatory cytokine signaling in brain areas implicated in mood regulation (mPFC; medial Prefrontal Cortex). Despite increasing evidence implicating impairments of neuroplasticity and synaptic signaling deficits into the pathophysiology of stress-related mental disorders, how microglia may modulate neuronal homeostasis in response to chronic stress has not been defined. Here, using the repeated social defeat stress (RSDS) mouse model we demonstrate that microglial-induced inflammatory responses are regulating neuronal plasticity associated with psychosocial stress. Specifically, we show that chronic stress induces a rapid activation and proliferation of microglia as well as macrophage infiltration in the mPFC, and these processes are spatially related to neuronal activation. Moreover, we report a significant association of microglial inflammatory responses with susceptibility or resilience to chronic stress. In addition, we find that exposure to chronic stress exacerbates phagocytosis of synaptic elements and deficits in neuronal plasticity. Importantly, by utilizing two different CSF1R inhibitors (the brain penetrant PLX5622 and the non-penetrant PLX73086) we highlight a crucial role for microglia (and secondarily macrophages) in catalyzing the pathological manifestations linked to psychosocial stress in the mPFC and the resulting behavioral deficits usually associated with depression.