Stress-related Mental Illness Research Articles

Transcriptomic analysis of rat prefrontal cortex following chronic stress induced by social isolation – Relevance to psychiatric and neurodevelopmental illness, and implications for treatment

Social isolation is an established risk factor for psychiatric illness, and became increasingly topical with the spread of SARS-CoV-2. We used RNA sequencing (RNA-Seq) to enable unbiased assessment of transcriptomic changes within the prefrontal cortex (PFC) of isolation-reared rats. To provide insight into the relevance of this manipulation for studying human illness, we compared differentially expressed genes (DEGs) and enriched biological functions against datasets involving post-mortem frontal cortical tissue from patients with psychiatric and neurodevelopmental illnesses. Sixteen male Sprague-Dawley rats were reared in groups of four or individually from weaning on postnatal day (PND) 22–24 until PFC tissue collection for RNA-Seq (PND64-66). We identified a total of 183 DEGs in isolates, of which 128 mirrored those in PFC tissue from patients with stress-related mental illnesses and/or neurodevelopmental conditions featuring social deficits. Seventy-one encode proteins classed as druggable by the gene-drug interaction database. Interestingly there are antagonists or inhibitors for the products of three of these up-regulated DEGs (Hrh3, Snca and Sod1) and agonists or activators for products of six of these down-regulated DEGs (Chrm4, Klf2, Lrrk2, Nr4a1, Nr4a3 and Prkca). Some have already undergone pre-clinical and clinical evaluation, and studies with the remainder may be warranted. Changes to Hrh3, Sod1, Chrm4, Lrrk2, Nr4a1 and Prkca were replicated in an independent cohort of sixteen male Sprague-Dawley rats via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Our findings support the continued use of post-weaning isolation rearing to investigate the neurobiology of stress-related disorders and evaluate therapeutic targets.

Designing Stress-Relieving Small Inner-City Park Environments for Teenagers

All over the world, teenagers suffer from stress-related mental illness, and research shows that being in natural environments can bring about recovery. However, centrally located areas in cities where teenagers like to hang out are being densified at the expense of green spaces. The health-promoting function of small, centrally located parks is thus becoming increasingly important. This study examines Iranian teenagers’ assessment of the restorative potential of small, centrally located parks. Such parks include attributes typical of city centers, such as trees, lighting, park benches and flowers. A discrete sampling method was used to collect responses from a sample of 265 Iranian teenagers. They were asked to randomly rate the perceived recovery potential of digitally designed models of green spaces. The results show that the teenagers evaluated the presence of water in waterbeds to have a strong positive effect on recovery possibilities. The entire green area should also be screened off from the rest of the city and convey a soft impression. It should have lighting from tall lampposts, contain plant beds and, not least, have distinctive cultural attributes such as crescent arches and fountains. In the discussion of the article, we address the practical and theoretical implications of the findings.

Multidimensional Effects of Stress on Neuronal Exosome Levels and Simultaneous Transcriptomic Profiles

BackgroundAn excess of exosomes, nanovesicles released from all cells and key regulators of brain plasticity, is an emerging therapeutic target for stress-related mental illnesses. The effects of chronic stress on exosome levels are unknown; even less is known about molecular drivers of exosome levels in the stress response. MethodsWe used our state-of-the-art protocol with 2 complementary strategies to isolate neuronal exosomes from plasma, ventral dentate gyrus, basolateral amygdala, and olfactory bulbs of male mice to determine the effects of chronic restraint stress (CRS) on exosome levels. Next, we used RNA sequencing and bioinformatic analyses to identify molecular drivers of exosome levels. ResultsWe found that CRS led to an increase in the levels of neuronal but not total (not neuronally enriched) exosomes assayed in plasma and the ventral dentate gyrus, whereas CRS led to a decrease in neuronal but not total exosome levels in the basolateral amygdala. There was a specificity of effects as shown by a lack of changes in olfactory bulb exosome levels. In pursuit of advancing translational applications, we showed that acetyl-L-carnitine administration restored a CRS-induced increase in neuronal exosome levels assayed in plasma (the most accessible specimen). Furthermore, CRS-induced transcriptional changes in the ventral dentate gyrus and basolateral amygdala mirrored the opposite pattern of CRS-induced changes in neuronal exosome levels, with β-estradiol signaling as a potential upstream driver of exosome levels. ConclusionsThis study provides a foundation for future studies of new forms of local and distant communication in stress neurobiology by demonstrating specific relationships between peripheral and central neuronal exosomes and providing new candidate targets for the normalization of exosome levels.

Increase in short-term and long-term stress-associated mental illness after Jiji earthquake in Taiwan: A twenty-year longitudinal population-based cohort study (1999–2019)

BackgroundEarthquakes have caused profound physical and mental health impacts in human history. The Jiji earthquake, which had a magnitude of 7.6 on the Richter scale, occurred on 21 September 1999 in Taiwan. A close follow-up on the mental health status of affected adults after major natural disasters to construct the short-term and long-term risk and prevalence of stress-associated mental illnesses has not been performed by using the nationwide health databases. MethodsThis population-based cohort study included 468,804 adults affected by Jiji earthquake spanning from 2000 to 2019 who were matched at a 1:4 ratio with unaffected individuals based on age and sex (n = 1,875,216). Employing a subdistribution hazard regression analysis, we assessed the incidence of sleep, anxiety, and depressive disorders after Jiji earthquake. Corrections for multiple comparisons were carried out using the Benjamini–Hochberg procedure. ResultsAffected adults experienced an increased incidence of short-term (approximately twice) stress-associated psychiatric disorders. The risk of the post-traumatic stress disorder (PTSD) is significantly higher in the affected adults (40–64 years: aSHR: 92.0; ≥65 years: aSHR: 96.7, p < 0.0001). Middle-aged (aged 40–64 years) male adults presented with significantly more short-term (< one year) and long-term (up to 20 years) stress-related mental illnesses, i.e., insomnia, anxiety, and depressive disorders, than individuals in the control group. ConclusionsAn earthquake has significant short and long-term effects on sleep quality, anxiety, and depressive disorders in affected adults. Optimal short and long-term close monitoring is needed to deploy medical resources and socioeconomic support to relieve mental stress burdens.

Anti-psychotic Nature of Antibiotics: Vancomycin and Omadacycline Combination Ameliorating Stress in a Zebrafish Model.

Background Stress affects mental health significantly and is a ubiquitous feature of contemporary living. Among the possible antibiotics are omadacycline and vancomycin, whose anti-inflammatory properties have also been thoroughly documented in recent research. The goal of the current study was to examine their complex involvement in the brain's stress response circuits and how they modulate stress. An established model organism that provides a useful platform for examining stress-induced behaviors and possible therapeutic approaches is the zebrafish. To investigate how dopamine affects the stress response, we used a zebrafish model that was exposed to stress. Methodology For three minutes, zebrafish were continually subjected to chasing stress. They were then given antibiotic combinations of 50 µg/mL each of vancomycin and omadacycline at various ratios of 1:1, 3:1, and 3:1. Behavior alterations, including freezing bouts, top-bottom ratios, and latency periods, were analyzed and contrasted with control groups. ImageJ software was utilized to analyze the video footage of the fish. Results The study showed that the combination of omadacycline and vancomycin greatly reduced the behaviors in zebrafish caused by stress. They chose their concentration (50 µg/mL) according to the lethal concentration 50% result. By shortening the latency time and increasing the intensity of breezing sessions, these chemicals restored almost normal activity.There was statistical significance in the outcomes. The results show that the combination of vancomycin and omadacycline may have an anti-psychotic impact on zebrafish behaviors brought on by stress. Their control of stress reactions is consistent with their known roles in the reward and stress circuits of the brain. These results emphasize the complex interactions between neurotransmitter systems and the control of stress, highlighting the therapeutic potential of dopamine in the treatment of stress-related mental illnesses. Conclusions The combination of vancomycin and omadacycline has been shown to have anti-psychotic effects, which presents potential opportunities for the development of new treatment strategies for mental diseases associated with stress. To fully understand the specific processes underpinning their involvement in stress management and how they relate to mental illnesses in humans, more investigation is necessary.

The Application of Nanotechnology and Nanomaterials in Depression: An Updated Review

&lt;img src=” https://s3.amazonaws.com/production.scholastica/article/82215/large/prnano_932023ga.jpg?1687987211”&gt; Depression is the most common stress-related mental illness. It has an impact on millions of individuals globally. Genetic, biochemical, environmental, and psychological elements can all play a role in its development. Medications, psychotherapy, and lifestyle changes are frequently used to treat depression. Antidepressant medications work by altering the levels of certain chem-icals in the brain. At the same time, psychotherapy aims to help individuals better understand and manage their emotions and thoughts, which otherwise may lead to depression. The current treatment strategy for the illness has several drawbacks, such as adverse effects, ineffectiveness, long-term use, stigma, and cost-related issues of the medication used. These negative effects un-derscore the need for more successful and novel methods of treating depression, such as the investigation of medication delivery techniques based on nanotechnology. Increased medication effectiveness, fewer side effects, long-lasting medication effects, a good understanding of the neural underpinnings of depression, and the potential for the creation of personalized medicines are some of the potential benefits of using nanotechnology in depressive disorder treatment. In several scientific domains, nanotechnology has many benefits. Nanoparticles are the fundamen-tal building blocks of nanotechnology in this regard. Nanoparticles hold great promise for use in medical applications, as recently developed nanotechnology has shown. This review focuses on the most popular nanomaterials that are used to treat depression, in addition to how well these nanomaterials are at managing depression based on their physical, chemical, and biological properties. We have also talked about the difficulties that the various nanomaterials face, which limit their uses and prevent the development of effective clinical therapies.

Investigating TSPO levels in occupation-related posttraumatic stress disorder

Microglia are immune brain cells implicated in stress-related mental illnesses including posttraumatic stress disorder (PTSD). Their role in the pathophysiology of PTSD, and on neurobiological systems that regulate stress, is not completely understood. We tested the hypothesis that microglia activation, in fronto-limbic brain regions involved in PTSD, would be elevated in participants with occupation-related PTSD. We also explored the relationship between cortisol and microglia activation. Twenty participants with PTSD and 23 healthy controls (HC) completed positron emission tomography (PET) scanning of the 18-kDa translocator protein (TSPO), a putative biomarker of microglia activation using the probe [18F]FEPPA, and blood samples for measurement of cortisol. [18F]FEPPA VT was non-significantly elevated (6.5–30%) in fronto-limbic regions in PTSD participants. [18F]FEPPA VT was significantly higher in PTSD participants reporting frequent cannabis use compared to PTSD non-users (44%, p = 0.047). Male participants with PTSD (21%, p = 0.094) and a history of early childhood trauma (33%, p = 0.116) had non-significantly higher [18F]FEPPA VT. Average fronto-limbic [18F]FEPPA VT was positively related to cortisol (r = 0.530, p = 0.028) in the PTSD group only. Although we did not find a significant abnormality in TSPO binding in PTSD, findings suggest microglial activation might have occurred in a subgroup who reported frequent cannabis use. The relationship between cortisol and TSPO binding suggests a potential link between hypothalamic–pituitary–adrenal-axis dysregulation and central immune response to trauma which warrants further study.

Molecular and cellular mechanisms for differential effects of chronic social isolation stress in males and females.

Chronic social isolation stress during adolescence induces susceptibility for neuropsychiatric disorders. Here we show that 5-week post-weaning isolation stress induces sex-specific behavioral abnormalities and neuronal activity changes in the prefrontal cortex (PFC), basal lateral amygdala (BLA), and ventral tegmental area (VTA). Chemogenetic manipulation, optogenetic recording, and in vivo calcium imaging identify that the PFC to BLA pathway is causally linked to heightened aggression in stressed males, and the PFC to VTA pathway is causally linked to social withdrawal in stressed females. Isolation stress induces genome-wide transcriptional alterations in a region-specific manner. Particularly, the upregulated genes in BLA of stressed males are under the control of activated transcription factor CREB, and CREB inhibition in BLA normalizes gene expression and reverses aggressive behaviors. On the other hand, neuropeptide Hcrt (Hypocretin/Orexin) is among the top-ranking downregulated genes in VTA of stressed females, and Orexin-A treatment rescues social withdrawal. These results have revealed molecular mechanisms and potential therapeutic targets for stress-related mental illness.

FKBP51 modulates hippocampal size and function in post-translational regulation of Parkin.

FK506-binding protein 51 (encoded by Fkpb51, also known as Fkbp5) has been associated with stress-related mental illness. To investigate its function, we studied the morphological consequences of Fkbp51 deletion. Artificial Intelligence-assisted morphological analysis revealed that male Fkbp51 knock-out (KO) mice possess more elongated dentate gyrus (DG) but shorter hippocampal height in coronal sections when compared to WT. Primary cultured Fkbp51 KO hippocampal neurons were shown to exhibit larger dendritic outgrowth than wild-type (WT) controls and pharmacological manipulation experiments suggest that this may occur through the regulation of microtubule-associated protein. Both in vitro primary culture and in vivo labeling support a role for FKBP51 in the regulation of microtubule-associated protein expression. Furthermore, Fkbp51 KO hippocampi exhibited decreases in βIII-tubulin, MAP2, and Tau protein levels, but a greater than 2.5-fold increase in Parkin protein. Overexpression and knock-down FKBP51 demonstrated that FKBP51 negatively regulates Parkin in a dose-dependent and ubiquitin-mediated manner. These results indicate a potential novel post-translational regulatory mechanism of Parkin by FKBP51 and the significance of their interaction on disease onset. KO has more flattened hippocampus using AI-assisted measurement Both pyramidal cell layer (PCL) of CA and granular cell layer (GCL) of DG distinguishable as two layers: deep cell layer and superficial layer.Distinct MAP2 expression between deep and superficial layer between KO and WT, Higher Parkin expression in KO brain Mechanism of FKBP51 inhibition resulting in Parkin, MAP2, Tau, and Tubulin expression differences between KO and WT mice, and resulting neurite outgrowth differences.

Early stress-induced impaired microglial pruning of excitatory synapses on immature CRH-expressing neurons provokes aberrant adult stress responses.

SUMMARYSeveral mental illnesses, characterized by aberrant stress reactivity, often arise after early-life adversity (ELA). However, it is unclear how ELA affects stress-related brain circuit maturation, provoking these enduring vulnerabilities. We find that ELA increases functional excitatory synapses onto stress-sensitive hypothalamic corticotropin-releasing hormone (CRH)-expressing neurons, resulting from disrupted developmental synapse pruning by adjacent microglia. Microglial process dynamics and synaptic element engulfment were attenuated in ELA mice, associated with deficient signaling of the microglial phagocytic receptor MerTK. Accordingly, selective chronic chemogenetic activation of ELA microglia increased microglial process dynamics and reduced excitatory synapse density to control levels. Notably, selective early-life activation of ELA microglia normalized adult acute and chronic stress responses, including stress-induced hormone secretion and behavioral threat responses, as well as chronic adrenal hypertrophy of ELA mice. Thus, microglial actions during development are powerful contributors to mechanisms by which ELA sculpts the connectivity of stress-regulating neurons, promoting vulnerability to stress and stress-related mental illnesses.

Resilience in Informal Caregivers of People Living with Dementia in the Face of COVID-19 Pandemic-Related Changes to Daily Life

Abstract. Informal caregivers of people living with dementia (PwD) are at increased risk for the development of stress-related physical and mental illness. Nevertheless, because of differing resilience, they show interindividual differences in their ability to cope. Particularly during the COVID-19 pandemic, with the associated pandemic control measures and pandemic-related changes to daily life, resilience might be further challenged, and stress might consequently increase. Therefore, we review the evidence on informal caregivers’ experience during the COVID-19 pandemic regarding effects of the pandemic control measures on (a) the caregiver’s health, (b) the care recipient’s health, (c) the stability of the care situation, and (d) coping in daily life. We conclude with implications on how to strengthen resilience and reduce stress in terms of environmental, social, and individual resources.

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.

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.

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.

Facing a blind alley - Experiences of stress-related exhaustion: a qualitative study

IntroductionMental illness is a major concern in many countries. In Sweden, stress-related mental illness is currently the most frequent reason for sick leave.ObjectiveThis study aimed to explore patients’ experiences of...

The association of PTSD symptom severity with amygdala nuclei volumes in traumatized youths

The amygdala is a core component in neurobiological models of stress and stress-related pathologies, including post-traumatic stress disorder (PTSD). While numerous studies have reported increased amygdala activity following traumatic stress exposure and in PTSD, the findings regarding amygdala volume have been mixed. One reason for these mixed findings may be that the amygdala has been considered as a homogenous entity, while it in fact consists of several nuclei with unique cellular and connectivity profiles. Here, we investigated amygdala nuclei volumes of the basolateral and the centrocorticomedial complex in relation to PTSD symptom severity in 47 young survivors from the 2011 Norwegian terror attack 24–36 months post-trauma. PTSD symptoms were assessed 4–5, 14–15 and 24–36 months following the trauma. We found that increased PTSD symptom severity 24–36 months post-trauma was associated with volumetric reductions of all basolateral as well as the central and the medial nuclei. However, only the lateral nucleus was associated with longitudinal symptom development, and mediated the association between 4–5 months and 24–36 months post-trauma symptoms. The results suggest that the amygdala nuclei may be differentially associated with cross-sectional and longitudinal measures of PTSD symptom severity. As such, investigations of amygdala total volume may not provide an adequate index of the association between amygdala and stress-related mental illness.

The growing issue of burnout in radiology - a survey-based evaluation of driving factors and potential impacts in pediatric radiologists.

Burnout in medicine, and specifically radiology, has been receiving more attention. Little data-driven literature is available regarding risk factors/causes to ultimately help guide the development of potential solutions. To survey pediatric radiologists, a cohort with a documented high prevalence of burnout, and to understand the impact of clinical demands on nonclinical tasks and the implications of burnout on mental health. A survey of Society for Pediatric Radiology (SPR) North America attendings was performed regarding institutional factors contributing to burnout, including call burden, clinical demands, departmental support and administrative/academic tasks. Questions regarding mental health and wellness resources were also included. Generalized linear modeling assuming binomial distribution was used for analyses with SAS 9.4. The response rate was 305/1,282 (24%) with 53% of respondents female. Respondents reported that both the number and complexity of clinical cases have increased since they first started practice as an attending, while the time for interpretation has not changed, P<0.0001. Using a scale of 0 (never), 1 (rarely), 2 (sometimes), 3 (frequently) and 4 (always), covering multiple hospitals (2.2) and administrative tasks (2.4) were the most stressful job factors. For those in administrative roles, the most stressful job factors were job-related tasks affected teaching duties (2.0) and decreased overall job satisfaction (2.0). Of the respondents, 52% said they know a physician affected by work stress-related mental illness and 25% know a physician who has contemplated or committed suicide. While 39% of the respondents have resources available to address burnout, only 33% utilize these resources. Increasing clinical demands and additional institutional/departmental factors play a potential role in burnout, which has serious implications for the mental health of pediatric radiologists.

Prefrontal Nectin3 Reduction Mediates Adolescent Stress-Induced Deficits of Social Memory, Spatial Working Memory, and Dendritic Structure in Mice

Chronic stress may disrupt the normal neurodevelopmental trajectory of the adolescent brain (especially the prefrontal cortex) and contribute to the pathophysiology of stress-related mental illnesses, but the underlying molecular mechanisms remain unclear. Here, we investigated how synaptic cell adhesion molecules (e.g., nectin3) are involved in the effects of adolescent chronic stress on mouse medial prefrontal cortex (mPFC). Male C57BL/6N mice were subjected to chronic social instability stress from postnatal days 29 to 77. One week later, the mice exposed to chronic stress exhibited impaired social recognition and spatial working memory, simplified dendritic structure, and reduced spine density in the mPFC. Membrane localization of nectin3 was also altered, and was significantly correlated with behavioral performance. Furthermore, knocking down mPFC nectin3 expression by adeno-associated virus in adolescent mice reproduced the stress-induced changes in behavior and mPFC morphology. These results support the hypothesis that nectin3 is a potential mediator of the effects of adolescent chronic stress on prefrontal structural and functional abnormalities.

Antidepressant-like effects of β-caryophyllene on restraint plus stress-induced depression

Chronic stress is depressogenic by altering neurotrophic and neuroinflammatory environments of the organism. The endocannabinoid system controls cognitive and emotional responses related with stress through the interaction with endocannabinoid receptors. β-Caryophyllene (BCP) is a CB2 agonist that exhibited anti-inflammatory, analgesic effects but minimal psychoactive effects.To test if BCP exhibits antidepressant-like action, animals were chronically restrained with additional stressors for 28 days, and BCP (25, 50, 100 mg/kg) was intraperitoneally injected once a day during the stress inflicting period. Then despair related behaviors and hippocampal expression of neurotrophic, inflammatory and cannabinoid receptor levels were measured. To test the effect of BCP on long-term depression, field potentials were measured during the application of lipopolysaccharide and low frequency stimulation.In the tail suspension test and forced swim test, chronic stress-induced despair behaviors were reduced by BCP. Also BCP improved the stress-related changes in the hippocampal expression of COX-2, BDNF, and CB2 receptor expression. In organotypic hippocampal slices, BCP reduced the lipopolysaccharide-induced intensification of the long-term depression. In conclusion, BCP improved chronic stress related behavioral and biochemical changes. These results suggest that BCP may be effective in treating depression and stress related mental illnesses.