Phenotypic Insights Into Anti-IgLON5 Disease in IgLON5-Deficient Mice.

BACKGROUND AND OBJECTIVES: Anti-IgLON5 disease is an autoimmune neurodegenerative disorder characterized by various phenotypes, notably sleep and movement disorders and tau pathology. Although the disease is known to be associated with the neuronal cell adhesion protein IgLON5, the physiologic function of IgLON5 remains elusive. There are conflicting views on whether autoantibodies cause loss of function, activation of IgLON5, or inflammation-associated neuronal damage, ultimately leading to the disease. We generated IgLON5 knockout (-/-) mice to investigate the functions of IgLON5 and elucidate the pathomechanism of anti-IgLON5 disease. METHODS: IgLON5 knockout (-/-) mice underwent behavioral tests investigating motor function, psychiatric function (notably anxiety and depression), social and exploratory behaviors, spatial learning and memory, and sensory perception. Histologic analysis was conducted to investigate tau aggregation in mice with tauopathy. RESULTS: IgLON5-/- mice had poorer performance in the wire hang and rotarod tests (which are tests for motor function) than wild-type mice. Moreover, IgLON5-/- mice exhibited decreased anxiety-like behavior and/or hyperactivity in behavior tests, including light/dark transition test and open field test. IgLON5-/- mice also exhibited poorer remote memory in the contextual fear conditioning test. However, neither sleeping disabilities assessed by EEG nor tau aggregation was detected in the knockout mice. DISCUSSION: These results suggest that IgLON5 is associated with activity, anxiety, motor ability, and contextual fear memory. Comparing the various phenotypes of anti-IgLON5 disease, anti-IgLON5 disease might partially be associated with loss of function of IgLON5; however, other phenotypes, such as sleep disorders and tau aggregation, can be caused by gain of function of IgLON5 and/or neuronal damage due to inflammation. Further studies are needed to elucidate the role of IgLON5 in the pathogenesis of anti-IgLON5 diseases.

Stress, pain, anxiety, and depression in endometriosis-Targeting glial activation and inflammation.

Endometriosis (EM) is a gynecological inflammatory disease often accompanied by stress, chronic pelvic pain (CPP), anxiety, and depression, leading to a diminished quality of life. This review aims to discuss the relationship between systemic and local inflammatory responses in the central nervous system (CNS), focusing on glial dysfunctions (astrocytes and microglia) as in critical brain regions involved in emotion, cognition, pain processing, anxiety, and depression. The review presents that EM is connected to increased levels of pro-inflammatory cytokines in the circulation. Additionally, chronic stress and CPP as stressors may contribute to the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, depleting the production of inflammatory mediators in the circulatory system and the brain. The systemic cytokines cause blood-brain barrier (BBB) breakdown, activate microglia in the brain, and lead to neuroinflammation. Furthermore, CPP may induce neuronal morphological alterations in critical regions through central sensitization and the activation of glial cells. The activation of glial cells, particularly the polarization of microglia, leads to the activation of the NLRP3 inflammasome and the overproduction of inflammatory cytokines. These inflammatory cytokines interact with the signaling pathways involved in neural plasticity. Additionally, persistent inflammatory conditions in the brain lead to neuronal death, which is correlated with a reduced volume of key brain regions such as the hippocampus. This review highlights the involvement of glial cells in the pathogenesis of the mental comorbidities of EM (i.e., pain, anxiety, and depression) and to discuss potential therapeutic approaches for targeting the inflammation and activation of microglia in key brain regions.

Childhood trauma and LPS-stimulated inflammation in adulthood: Results from the Netherlands Study of Depression and Anxiety

BACKGROUND: Childhood trauma (CT) is robustly associated with psychiatric disorders including major depressive and anxiety disorders across the life span. The innate immune system may play a role in the relation between CT and stress-related psychopathology. However, whether CT influences the innate production capacity of cytokine levels following ex vivo stimulation by lipopolysaccharide (LPS), is currently unknown. METHODS: Using data from the Netherlands Study of Depression and Anxiety (NESDA, n=1237), we examined whether CT (emotional neglect, emotional, physical, and sexual abuse before the age of 16), assessed by the Childhood Trauma Interview, was associated with levels in supernatants of interferon (IFN)γ, interleukin-2 (IL-2), IL-4, IL-6, IL-8, IL-10, IL-18, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1α, MIP-1ß, matrix metalloproteinase-2 (MMP-2), TNFα and TNFß after ex vivo stimulation with LPS. Cytokines were analysed individually and cumulatively (overall inflammation index and number of cytokines in high-risk quartile (HRQ)) using linear regression analyses. RESULTS: After adjustment for demographic, lifestyle, and health-related covariates, total CT severity was associated with the overall inflammation index (ß = 0.085, PFDR = 0.011), the number of cytokines in HRQ (ß = 0.063, PFDR = 0.036), and individual markers of IL-2 (ß = 0.067, PFDR = 0.036), IL-6 (ß = 0.091 PFDR = 0.011), IL-8 (ß = 0.085 PFDR = 0.011), IL-10 (ß = 0.094 PFDR = 0.011), MCP-1 (ß = 0.081 PFDR = 0.011), MIP-1α (ß = 0.061 PFDR = 0.047), MIP1-ß (ß = 0.077 PFDR = 0.016), MMP-2 (ß = 0.070 PFDR = 0.027), and TNFß (ß = 0.078 PFDR = 0.016). Associations were strongest for individuals with severe CT, reporting multiple types or higher frequencies of trauma. Half of the findings persisted after adjustment for psychiatric status. The findings were consistent across different CT types. CONCLUSION: Childhood Trauma is associated with increased LPS-stimulated cytokine levels, with evidence for a dose-response relationship. Our results highlight a dysregulated innate immune system capacity in adults with CT, which could contribute to an increased vulnerability for psychopathology and somatic disorders across the lifespan.

Coptisine Alleviates Imiquimod-Induced Psoriasis-like Skin Lesions and Anxiety-like Behavior in Mice.

Psoriasis is a common inflammatory skin disorder, which can be associated with psychological disorders, such as anxiety and depression. This study investigated the efficacy and the mechanism of action of a natural compound coptisine using imiquimod (IMQ)-induced psoriasis mice. Coptisine reduced the severity of psoriasis-like skin lesions, decreased epidermal hyperplasia and the levels of inflammatory cytokines TNF-α, IL-17, and IL-22. Furthermore, coptisine improved IMQ-induced anxiety in mice by increasing the number of entries and time in open arms in the elevated plus maze (EPM) test. Coptisine also lowered the levels of inflammatory cytokines TNF-α and IL-1ß in the prefrontal cortex of psoriasis mice. HaCaT keratinocytes and BV2 microglial cells were used to investigate the effects of coptisine in vitro. In M5-treated HaCaT cells, coptisine decreased the production of IL-6, MIP-3α/CCL20, IP-10/CXCL10, and ICAM-1 and suppressed the NF-κB signaling pathway. In LPS-stimulated BV2 cells, coptisine reduced the secretion of TNF-α and IL-1ß. These findings suggest that coptisine might be a potential candidate for psoriasis treatment by improving both disease severity and psychological comorbidities.

Innate immune stimulation by monophosphoryl lipid A prevents chronic social defeat stress-induced anxiety-like behaviors in mice.

BACKGROUND: Innate immune pre-stimulation can prevent the development of depression-like behaviors in chronically stressed mice; however, whether the same stimulation prevents the development of anxiety-like behaviors in animals remains unclear. We addressed this issue using monophosphoryl lipid A (MPL), a derivative of lipopolysaccharide (LPS) that lacks undesirable properties of LPS but still keeps immune-enhancing activities. METHODS: The experimental mice were pre-injected intraperitoneally with MPL before stress exposure. Depression was induced through chronic social defeat stress (CSDS). Behavioral tests were conducted to identify anxiety-like behaviors. Real-time polymerase chain reaction (PCR) and biochemical assays were employed to examine the gene and protein expression levels of pro-inflammatory markers. RESULTS: A single MPL injection at the dose of 400 and 800 µg/kg 1 day before stress exposure prevented CSDS-induced anxiety-like behaviors, and a single MPL injection (400 µg/kg) five but not 10 days before stress exposure produced similar effect. The preventive effect of MPL on anxiety-like behaviors was also observed in CSDS mice who received a second MPL injection 10 days after the first MPL injection or a 4 × MPL injection 10 days before stress exposure. MPL pre-injection also prevented the production of pro-inflammatory cytokines in the hippocampus and medial prefrontal cortex in CSDS mice, and inhibiting the central immune response by minocycline pretreatment abrogated the preventive effect of MPL on CSDS-induced anxiety-like behaviors and pro-inflammatory cytokine productions in the brain. CONCLUSIONS: Pre-stimulation of the innate immune system by MPL can prevent chronic stress-induced anxiety-like behaviors and neuroinflammatory responses in the brain in mice.

Innate immune stimulation prevents the development of anxiety-like behaviors in chronically stressed mice.

Anxiety is a common psychological disease which can induce severe social burdens. Searching methods that prevent the onset of anxiety is of great significance for ameliorating the social and individual problems induced by this type of disease. In this study, we investigated how innate immune pre-stimulation influences the anxiety-like behaviors in chronically stressed mice. Our results showed that a single injection of an innate immune stimulant lipopolysaccharide (LPS) at the dose of 50, 100, and 500 µg/kg 1 day before stress exposure prevented chronic social defeat stress (CSDS)-induced anxiety-like behaviors in mice. A single injection of LPS (100 µg/kg) 5 days before stress exposure produced similar preventive effects on CSDS-induced anxiety-like behaviors, while similar effects were not observed at the condition of 10-days interval between LPS injection and stress exposure. A second LPS injection 10 days after the first LPS injection or a 4 × LPS injection 10 days before stress exposure also prevented CSDS-induced anxiety-like behaviors. Moreover, a single injection of LPS (100 µg/kg) 1 day before stress exposure prevented the production of pro-inflammatory cytokines in the hippocampus and prefrontal cortex of CSDS mice. Suppression of innate immune stimulation by minocycline pretreatment simultaneously abrogated the preventive effect of LPS pre-injection (100 µg/kg) on CSDS-induced anxiety-like behaviors and pro-inflammatory cytokine production in the brain. Our results demonstrated that the pre-stimulation of the innate immune system can prevent the development of anxiety-like behaviors and the progression of the neuroinflammatory responses in the brain in chronically stressed mice.

Chemokine profile in women with moderate to severe anxiety and depression during pregnancy.

BACKGROUND: Cytokine levels have been extensively described in pregnant subjects under normal and pathological conditions, including mood-related disorders. Concerning chemokines, very few studies have reported their association with psychiatric disorders during pregnancy. Therefore, we explored the chemokine profile in women exhibiting anxiety and depression during late pregnancy in the present study. METHODS: One hundred twenty-six pregnant women in the 3rd trimester of pregnancy, displaying moderate to severe anxiety (ANX) alone and women exhibiting moderate to severe anxiety with comorbid depression (ANX + DEP), and 40 control pregnant women without affective disorders (CTRL) were evaluated through the Hamilton Anxiety Rating Scale (HARS) and the Hamilton Depression Rating Scale (HDRS). Serum chemokine levels of MCP-1 (CCL2), RANTES (CCL5), IP-10 (CXCL10), Eotaxin (CCL11), TARC (CCL17), MIP-1α (CCL3), MIP-1ß (CCL4), MIG (CXCL9), MIP-3α (CCL20), ENA-78 (CXCL5), GROα (CXCL1), I-TAC (CXCL11) and IL-8 (CXCL8)] were measured by immunoassay. Clinical, biochemical, and sociodemographic parameters were correlated with HARS and HDRS score values. RESULTS: Serum levels of most chemokines were significantly higher in the ANX and in the ANX + DEP groups, when compared to the CTRL group. Positive correlations were observed between MIP-1α/CCL3, MIP-1ß/CCL4, MCP-1/CCL2, MIP-3α/CCL20, RANTES/CCL5, Eotaxin/CCL11, and I-TAC/CXCL11 with high scores for anxiety (HARS) (p < 0.05) and for depression (HDRS) (p < 0.004). After controlling clinical measures for age + gwk + BMI, chemokines such as IL-8/CXCL8, MCP-1/CCL2 and MIP-1ß/CCL4 were found associated with high scores for anxiety (p < 0.05) in the ANX group. TARC/CCL17 and Eotaxin/CCL11 showed significant associations with high scores for depression (p < 0.04) whereas, MCP-1/CCL2 and MIP-1α/CCL3 were significantly associated with high scores for anxiety (p < 0.05) in the ANX + DEP group. Using a multivariate linear model, high serum levels of MIP-1ß/CCL4 and Eotaxin/CCL11 remained associated with depression (p < 0.01), while, IL-8/CXCL8, MIP-1ß/CCL4, MCP-1/CCL2, and MIP-1α/CCL3 were associated with anxiety (p < 0.05) in the symptomatic groups. CONCLUSIONS: Our data show that serum levels of distinct chemokines are increased in women exhibiting high levels of affective symptoms during late pregnancy. Our results suggest that increased levels of anxiety, depressive symptoms, and mood-related disorders may promote changes in specific functional chemokines associated with a chronic inflammatory process. If not controlled, it may lead to adverse obstetric and negative neonate outcomes, child development and neuropsychiatric alterations in the postnatal life. HIGHLIGHTS: Chemokine levels increase in affective disorders during pregnancy.

Major Depressive Disorder Enhances Th2 and Th17 Cytokines in Patients Suffering from Allergic Rhinitis and Asthma.

INTRODUCTION: Major depressive disorder (MDD) can impact the severity of allergic rhinitis (AR) and asthma (AA). Here, we evaluated the cytokine production by T-cells from AR and AA patients with or without MDD. The effect of serotonin on the in vitro T-cell response was also evaluated. METHODS: The cytokines produced by activated T-cells were measured by Luminex and flow cytometry. In some cell cultures, serotonin was added. RESULTS: MDD not only enhanced the production of Th2- and Th17-related cytokines, but also, the levels of interleukin (IL)-5 and IL-17 were directly correlated with the severity of depression and anxiety symptoms. As compared with AR, the levels of IL-17 were higher and the release of IL-10 was lower in activated T-cell cultures from AA patients, mainly those with MDD. In AA/MDD patients, the severity of anxiety symptoms and lung disease was directly correlated with Th17-like and hybrid Th2/Th17 cells, but inversely correlated with IL-10-secreting CD4+ T-cells. Finally, the addition of serotonin reduced the production of Th2- and Th17-related cytokines, but elevated IL-10 secretion in cell cultures from both AR and AA patients. CONCLUSIONS: Our findings suggest that not only the occurrence of MDD but also the severity of anxiety symptoms, may adversely affect the outcome of allergic reactions by favoring the production of cytokines implicated in the pathogenesis of AR and AA, a phenomenon that was attenuated by serotonin.

Chronic Stress-Induced Depression and Anxiety Priming Modulated by Gut-Brain-Axis Immunity.

Chronic stress manifests as depressive- and anxiety-like behavior while recurrent stress elicits disproportionate behavioral impairments linked to stress-induced immunological priming. The gut-brain-microbiota-axis is a promising therapeutic target for stress-induced behavioral impairments as it simultaneously modulates peripheral and brain immunological landscapes. In this study, a combination of probiotics and prebiotics, known as a synbiotic, promoted behavioral resilience to chronic and recurrent stress by normalizing gut microbiota populations and promoting regulatory T cell (Treg) expansion through modulation of ileal innate lymphoid cell (ILC)3 activity, an impact reflecting behavioral responses better than limbic brain region neuroinflammation. Supporting this conclusion, a multivariate machine learning model correlatively predicted a cross-tissue immunological signature of stress-induced behavioral impairment where the ileal Treg/T helper17 cell ratio associated to hippocampal chemotactic chemokine and prefrontal cortex IL-1ß production in the context of stress-induced behavioral deficits. In conclusion, stress-induced behavioral impairments depend on the gut-brain-microbiota-axis and through ileal immune regulation, synbiotics attenuate the associated depressive- and anxiety-like behavior.

Immunomodulation Eliminates Inflammation in the Hippocampus in Experimental Autoimmune Encephalomyelitis, but Does Not Ameliorate Anxiety-Like Behavior.

Multiple sclerosis (MS) is an autoimmune disease targeting the central nervous system, characterized by an unpredictable disease course and a wide range of symptoms. Emotional and cognitive deficits are now recognized as primary disease manifestations and not simply the consequence of living with a chronic condition, raising questions regarding the efficacy of current therapeutics for these specific symptoms. Mechanisms underlying psychiatric sequelae in MS are believed to be similar to those underlying pathogenesis, that is mediated by cytokines and other inflammatory mediators. To gain insight into the pathogenesis of MS depression, we performed behavioral assays in the murine experimental autoimmune encephalomyelitis (EAE) MS model, in the presence or absence of immunomodulation using the drug FTY720, an analogue of the lipid signaling molecule sphingosine-1-phosphate (S1P). Specifically, mice were challenged with the elevated plus maze (EPM) test, a validated experimental paradigm for rodent-specific anxiety-like behavior. FTY720 treatment failed to ameliorate anxiety-like symptoms, irrespective of dosage. On the other hand, it was effective in reducing inflammatory infiltration, microglial reactivity and levels of pro-inflammatory molecules in the hippocampus, confirming the anti-inflammatory capacity of treatment. To explore the absence of FTY720 effect on behavior, we confirmed expression of S1P receptors (S1PR) S1PR1, S1PR3 and S1PR5 in the hippocampus and mapped the dynamics of these receptors in response to drug treatment alone, or in combination with EAE induction. We identified a complex pattern of responses, differing between (1) receptors, (2) dosage and (3) hippocampal sub-field. FTY720 treatment in the absence of EAE resulted in overall downregulation of S1PR1 and S1PR3, while S1PR5 exhibited a dose-dependent upregulation. EAE induction alone resulted in overall downregulation of all three receptors. On the other hand, combined FTY720 and EAE showed generally no effect on S1PR1 and S1PR3 expression except for the fimbrium region, but strong upregulation of S1PR5 over the range of doses examined. These data illustrate a hitherto undescribed complexity of S1PR response to FTY720 in the hippocampus, independent of drug effect on effector immune cells, but simultaneously emphasize the need to explore novel treatment strategies to specifically address mood disorders in MS.

Dexmedetomidine alleviates neuroinflammation, restores sleep disorders and neurobehavioral abnormalities in rats with minimal hepatic encephalopathy.

The occurrence and progress of minimal hepatic encephalopathy (MHE) is closely related to the inflammatory response; however, inflammation contributes to behavioral abnormalities and sleep disorders. Dexmedetomidine has anti-inflammatory effects against various diseases. Whether dexmedetomidine improves MHE and the underlying mechanism is yet unclear. The present study aimed to explore the effects of dexmedetomidine on sleep structure, neurobehavior, and brain morphology of MHE rats and investigate its underlying mechanism. A rat MHE model was established by intraperitoneal injection of thioacetamide (TAA). Dexmedetomidine or yohimbine was administered intraperitoneally to investigate the role of α2 adrenoreceptor in the protection conferred by dexmedetomidine. The 24-h sleep, neurobehavioral changes, the liver function, blood ammonia and morphological changes of the liver and brain were assessed. Also, the microglia, astrocytes, neurons, the expression of pro-inflammatory factors (IL-1ß, TNF-α, IL-18), and NLRP3 inflammasomes were detected. The results showed that marked sleep disorders, cognitive impairment, anxiety, abnormal liver function and pathological damage of liver and brain were detected in the MHE rats. The microglia in the prefrontal cortex was highly activated along with the increased expression of pro-inflammatory factors and NLRP3 inflammasomes. Interestingly, dexmedetomidine improved above indicators, however, yohimbine significantly abolished the protection of dexmedetomidine. These findings showed that dexmedetomidine restored the changes in the sleep disorders and neurobehavior in rats and reduced brain damage. The mechanism might be partially related to the activation of α2 adrenergic receptors, reduction of neuroinflammatory response, and inhibition of the activation of microglia and NLRP3/Caspase1 signaling pathway.

Primary care provider-reported prevalence of vaccine and polyethylene glycol allergy in Canada.

BACKGROUND: The coronavirus disease 2019 pandemic has highlighted the importance of accurate capture of vaccine, and vaccine component, allergy. There remains a gap in the prevalence literature from the perspective of direct primary care provider (PCP) reporting at a population level. OBJECTIVE: To determine the prevalence of PCP-documented vaccine and polyethylene glycol (PEG) allergy using electronic medical record data from the Canadian Primary Care Sentinel Surveillance Network. METHODS: Retrospective cohort study using the Canadian Primary Care Sentinel Surveillance Network repository. Machine learning algorithms were applied to evaluate for vaccine allergy documentation, and Anatomic Therapeutic Chemical codes were used for PEG allergy or allergy to common injectable medications containing PEG (CIMCP). RESULTS: The prevalence of PCP-documented vaccine allergy in Canada was 0.037% (395/1,055,677) and of PEG allergy was 0.0009% (10/1,055,677). In total, 0.01% of patients had a documented allergy to either PEG or CIMCP (135/1,055,677). None of the patients with PEG allergy had a documented allergy to a CIMCP. Patients with vaccine allergy and PEG allergy were significantly more likely to have other atopic comorbidities, including asthma (P < .001 for both), eczema (P < .001 and P = .001, respectively), rhinitis (P = .002 and P < .001, respectively), and food allergy (P < .001 for both). Significantly higher rates of depression (P < .001 and P < .001, respectively) and anxiety (P = .003 and P < .001, respectively) were found in those with vaccine allergy, or PEG allergy, than those without vaccine allergy or PEG allergy. CONCLUSION: This is the first study to estimate the prevalence of vaccine and PEG allergy in a national cohort that uses PCP documentation, revealing a low reported rate of vaccine allergy and PEG allergy.

Is Anxiety Associated with the Gut Microbiota?

Understanding how the microbiome influences health and disease has emerged as an important area of research across all domains of biomedical and health sciences. An extensive body of work in animal models has established a link between the gut microbiome and anxiety-like behaviour. Foundational work on germ-free mice provided the catalyst for neuroscientists to consider the microbiota-brain axis and brain health. Research manipulating the microbiome, including use of germ-free mice, antibiotics, and probiotics, provide evidence that the microbiota influences stress systems and in particular anxiety-like behaviour. Consideration of anxiety-like behaviour in animal models of metabolic and inflammatory disorders expands the scope of the work and correlates in clinical studies are emerging. This chapter highlights the work done to date in animal studies and reviews the recent clinical literature translating these observations to anxiety disorders.

Obesity Prevents S-Adenosylmethionine-Mediated Improvements in Age-Related Peripheral and Hippocampal Outcomes.

BACKGROUND: Age predisposes individuals to a myriad of disorders involving inflammation; this includes stress-related neuropsychiatric disorders such as depression and anxiety, and neurodegenerative diseases. Obesity can further exacerbate these effects in the brain. We investigated whether an inexpensive dietary supplement, s-adenosylmethionine (SAMe), could improve age- and/or obesity-related inflammatory and affective measures in the hippocampus. METHODS: Mice were placed on their diets at six weeks of age and then aged to 14 months, receiving SAMe (0.1 g/kg of food) for the final six weeks of the experiment. Prior to tissue collection, mice were tested for anxiety-like behaviors in the open field test and for metabolic outcomes related to type 2 diabetes. RESULTS: SAMe treatment significantly improved outcomes in aged control mice, where fasting glucose decreased, liver glutathione levels increased, and hippocampal microglia morphology improved. SAMe increased transforming growth factor ß-1 mRNA in both control mice, potentially accounting for improved microglial outcomes. Obese mice demonstrated increased anxiety-like behavior, where SAMe improved some, but not all, open field measures. CONCLUSIONS: In summary, SAMe boosted antioxidant levels, improved diabetic measures, and hippocampal inflammatory and behavioral outcomes in aged mice. The effects of SAMe in obese mice were more subdued, but it could still provide some positive outcomes for obese individuals dealing with anxiety and having difficulty changing their behaviors to improve health outcomes.

Effects of anxiety sensitivity, disgust, and intolerance of uncertainty on the COVID stress syndrome: a longitudinal assessment of transdiagnostic constructs and the behavioural immune system.

Excessive fear and worry in response to the COVID-19 pandemic (e.g., COVID stress syndrome) is prevalent and associated with various adverse outcomes. Research from the current and past pandemics supports the association between transdiagnostic constructs-anxiety sensitivity (AS), disgust, and intolerance of uncertainty (IU)-and pandemic-related distress. Recent research suggests a moderating effect of disgust on the relationship of AS-physical concerns and COVID-19-related distress, suggesting that transdiagnostic constructs underlie individual differences in activation of the behavioral immune system (BIS). No previous study has examined the independent and conjoint effects of pre-COVID-19 AS-physical concerns, disgust propensity (DP), disgust sensitivity (DS), and IU in this context; thus, we did so using longitudinal survey data (N = 3,062 Canadian and American adults) with simple and moderated moderations controlling for gender, mental health diagnosis, and COVID-19 diagnosis. Greater AS-physical concerns, DP, and DS predicted more severe COVID stress syndrome assessed one month later. Either DP or DS further amplified the effect of AS-physical concerns on COVID stress syndrome, except danger and contamination fears. IU did not interact with AS-physical concerns and DS or DP. Theoretical and clinical implications pertaining to delivery of cognitive behavioural therapy for pandemic-related distress are discussed.

Microglial deletion and inhibition alleviate behavior of post-traumatic stress disorder in mice.

BACKGROUND: Alteration of immune status in the central nervous system (CNS) has been implicated in the development of post-traumatic stress disorder (PTSD). However, the nature of overall changes in brain immunocyte landscape in PTSD condition remains unclear. METHODS: We constructed a mouse PTSD model by electric foot-shocks followed by contextual reminders and verified the PTSD-related symptoms by behavior test (including contextual freezing test, open-field test, and elevated plus maze test). We examined the immunocyte panorama in the brains of the naïve or PTSD mice by using single-cell mass cytometry. Microglia number and morphological changes in the hippocampus, prefrontal cortex, and amygdala were analyzed by histopathological methods. The gene expression changes of those microglia were detected by quantitative real-time PCR. Genetic/pharmacological depletion of microglia or minocycline treatment before foot-shocks exposure was performed to study the role of microglia in PTSD development and progress. RESULTS: We found microglia are the major brain immune cells that respond to PTSD. The number of microglia and ratio of microglia to immunocytes was significantly increased on the fifth day of foot-shock exposure. Furthermore, morphological analysis and gene expression profiling revealed temporal patterns of microglial activation in the hippocampus of the PTSD brains. Importantly, we found that genetic/pharmacological depletion of microglia or minocycline treatment before foot-shock exposure alleviated PTSD-associated anxiety and contextual fear. CONCLUSION: Our results demonstrated a critical role for microglial activation in PTSD development and a potential therapeutic strategy for the clinical treatment of PTSD in the form of microglial inhibition.

High anxiety and health-related quality of life in families with children with food allergy during coronavirus disease 2019.

BACKGROUND: Food allergy has a known effect on quality of life (QoL), but this has not been extensively studied during the coronavirus disease 2019 pandemic. OBJECTIVE: To characterize the levels of anxiety of mothers of children aged 0 to 8 years with food allergy compared with families of children without a food allergy and the health-related QoL among children with food allergy during the coronavirus disease 2019 pandemic. METHODS: In a mixed-methods study, Canadian mothers of children aged 0 to 8 years with (cases) and without (controls) food allergy provided demographic data and completed age-appropriate anxiety questionnaires between April 14, 2020, and April 28, 2020. The cases also provided food allergy-related data and completed the Food Allergy Quality of Life Questionnaire. In-depth interviews were subsequently conducted with purposefully selected cases. RESULTS: In a total of 580 participants, 5.5% were cases and 94.5% were controls. For mothers of children aged 0 to 1.5 years, anxiety levels did not differ between cases and controls. For mothers of children aged 1.5 to 8 years, anxiety levels were higher in cases vs controls (P < .05). Among the cases, neither overall nor domain-specific Food Allergy Quality of Life Questionnaire scores differed between age groups (0-3 vs 4-7 years), even after adjustment for confounding variables, including childcare during the pandemic. Qualitatively, the following 3 themes were identified: unexpected challenges of food shopping; less food-related food anxiety during the pandemic; and differences and delays in food allergy testing and therapy. CONCLUSION: Mothers of children with food allergy reported high anxiety and poor health-related QoL. Yet, qualitatively, day-to-day food allergy management was better during the pandemic.

Inhaled corticosteroids as treatment for adolescent asthma: effects on adult anxiety-related outcomes in a murine model.

RATIONALE: Allergic asthma, typically controlled with inhaled corticosteroids (ICS), is the leading chronic health condition for youth under 18 years of age. During this peri-adolescent period, significant brain maturation occurs. Prior studies indicate that both chronic inflammation and corticosteroid medications increase risk for developing an internalizing disorder like anxiety. OBJECTIVES: To determine if chronic ICS treatments exacerbate or alleviate anxiety symptoms associated with developmental allergic asthma, we used a mouse model to isolate the influence of ICS (fluticasone propionate, FLU) vs. airway inflammation (induced with house dust mite extract, HDM). METHODS: During development, male and female BALB/cJ mice were repeatedly exposed to HDM or saline plus one of four FLU doses (none/vehicle, low, moderate, or high). In adulthood, we assessed lung inflammation, circulating and excreted corticosteroids, anxiety-like behavior, and gene expression in stress and emotion regulation brain regions. RESULTS: FLU treatment decreased body weight and anxiety-like behavior and increased fecal corticosterone metabolite concentrations and Crhr2 gene expression in ventral hippocampus. FLU effects were only observed in saline/non-HDM-exposed mice, and the FLU doses used did not significantly decrease HDM-induced airway inflammation. Females had greater serum and fecal corticosterone concentrations, less anxiety-like behavior, and lower Crhr1 gene expression in ventral hippocampus and prefrontal cortex than males. CONCLUSIONS: These findings suggest that steroid medications for youth with allergic asthma may not exacerbate anxiety-related symptoms, and that they should be avoided in children/adolescents without a health condition. The results are informative to future work on the use of corticosteroid medications during childhood or adolescent development.