RESUMO
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.
Assuntos
Experiências Adversas da Infância , Ansiedade , Depressão , Imunidade Inata , Adulto , Ansiedade/imunologia , Transtornos de Ansiedade/imunologia , Quimiocina CCL2 , Quimiocina CCL3 , Quimiocina CCL4 , Citocinas/metabolismo , Depressão/imunologia , Transtorno Depressivo Maior/imunologia , Humanos , Inflamação , Interferons , Interleucina-10 , Interleucina-18 , Interleucina-2 , Interleucina-4 , Interleucina-6 , Interleucina-8 , Lipopolissacarídeos , Metaloproteinase 2 da Matriz , Países Baixos/epidemiologia , Fator de Necrose Tumoral alfaRESUMO
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.
Assuntos
Envelhecimento/imunologia , Ansiedade/dietoterapia , Hipocampo/efeitos dos fármacos , Obesidade/complicações , S-Adenosilmetionina/administração & dosagem , Animais , Ansiedade/diagnóstico , Ansiedade/imunologia , Ansiedade/metabolismo , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Modelos Animais de Doenças , Glutationa/análise , Glutationa/metabolismo , Hipocampo/imunologia , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Inflamação/dietoterapia , Inflamação/imunologia , Resistência à Insulina , Fígado/patologia , Masculino , Camundongos , Camundongos Obesos , Obesidade/imunologia , Obesidade/metabolismo , Obesidade/patologia , Fator de Crescimento Transformador beta1/análise , Fator de Crescimento Transformador beta1/metabolismoRESUMO
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.
Assuntos
Ansiedade/psicologia , Asco , Medo/psicologia , Estresse Psicológico/psicologia , Incerteza , Adulto , Idoso , Ansiedade/imunologia , Transtornos de Ansiedade/imunologia , Transtornos de Ansiedade/psicologia , COVID-19 , Teste para COVID-19 , Canadá , Feminino , Humanos , Sistema Imunitário/imunologia , Masculino , Pessoa de Meia-Idade , Pandemias , Estresse Psicológico/imunologiaRESUMO
As the infected cases of COVID-19 reach more than 20 million with more than 778,000 deaths globally, an increase in psychiatric disorders including anxiety and depression has been reported. Scientists globally have been searching for novel therapies and vaccines to fight against COVID-19. Improving innate immunity has been suggested to block progression of COVID-19 at early stages, while omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been shown to have immunomodulation effects. Moreover, n-3 PUFAs have also been shown to improve mood disorders, thus, future research is warranted to test if n-3 PUFAs may have the potential to improve our immunity to counteract both physical and mental impact of COVID-19.
Assuntos
Ansiedade/prevenção & controle , Infecções por Coronavirus/prevenção & controle , Depressão/prevenção & controle , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Fatores Imunológicos/administração & dosagem , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Ansiedade/imunologia , Ansiedade/metabolismo , Ansiedade/virologia , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , COVID-19 , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Citocinas/biossíntese , Citocinas/imunologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Células Dendríticas/virologia , Depressão/imunologia , Depressão/metabolismo , Depressão/virologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/virologia , Ácidos Graxos Ômega-3/imunologia , Ácidos Graxos Ômega-3/metabolismo , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/imunologia , Fatores Imunológicos/metabolismo , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Linfócitos/virologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/virologia , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , SARS-CoV-2RESUMO
BACKGROUND: The incidence of lung cancer is increasing annually. Clinicians pay special attention to lung tests during physical examinations. Due to the popularity of low-dose computed tomography, not only can lung cancer be diagnosed early, but physical examinations often reveal the presence of pulmonary nodules, an important health issue that cannot be ignored. Patients with pulmonary nodules are prone to adverse emotions such as anxiety and depression. Many studies have shown that patients with emotional disorders have immune system dysfunction and changes in inflammation levels. This study aimed to investigate the changes in anxiety, depression, the ratios of T helper cells 17 (Th17) and regulatory T cells (Tregs), and inflammation levels in patients with pulmonary nodules. METHODS: A total of 143 subjects from The First Affiliated Hospital of Anhui Medical University were included from April 2019 to July 2019. All of the subjects were assessed with the Beck Anxiety Inventory (BAI) and the Beck Depression Inventory-II (BDI-II). Overall, 40 cases were healthy controls (HC) and 103 cases were patients with pulmonary nodules. The patients were divided into two groups according to the scale scores: 62 cases in a non-anxiety and non-depression (NAD) group and 41 cases in an anxiety and/or depression (AD) group. The percentage of Th17 and Tregs in the peripheral blood and inflammatory factors in the serum were detected. The absolute Th17 cell counts were calculated and the differences between the groups and correlations between these indicators were analyzed. RESULTS: There were statistically significant differences in the percentage of Th17 cells, the absolute counts of Th17 and Th17/Treg cells, and the levels of interleukin-2 (IL-2), IL-6, and tumor necrosis factor-α (TNF-α) among three groups (all P<0.001). The AD group was higher than the HC and NAD groups (all P<0.05). There was no statistically significant difference between the HC and NAD groups (all P>0.05). The previously described indicators had no significant correlation with the severity of anxiety and depression (P>0.05). There were no significant differences in the percentage of Tregs or levels of IL-4 and IL-10 between the groups (all P>0.05). The proportion of anxiety and/or depression in female patients with pulmonary nodules was higher than that in males (P<0.05). CONCLUSIONS: Patients with pulmonary nodules are prone to varying degrees of anxiety and depression, which leads to immune dysfunction and low-grade inflammation.
Assuntos
Ansiedade/complicações , Ansiedade/imunologia , Depressão/complicações , Depressão/imunologia , Neoplasias Pulmonares/complicações , Linfócitos T Reguladores/citologia , Células Th17/citologia , Feminino , Humanos , Inflamação/complicações , Neoplasias Pulmonares/psicologia , Masculino , Pessoa de Meia-IdadeRESUMO
Since the end of 2019, Corona Virus Disease 2019 (COVID-19) has been the cause of a worldwide pandemic. The mental status of patients with COVID-19 who have been quarantined and the interactions between their psychological distress and physiological levels of inflammation have yet to be analyzed. Using a mixed-method triangulation design (QUAN + QUAL), this study investigated and compared the mental status and inflammatory markers of 103 patients who, while hospitalized with mild symptoms, tested positive with COVID-19 and 103 matched controls that were COVID-19 negative. The severity of depression, anxiety, and post-traumatic stress symptoms (PTSS) was measured via an on-line survey. Using a convenience sampling technique, qualitative data were collected until the point of data saturation. In addition, a semi-structured interview was conducted among five patients with COVID-19. Peripheral inflammatory markers were also collected in patients, both at baseline and within ± three days of completing the on-line survey. Results revealed that COVID-19 patients, when compared to non-COVID controls, manifested higher levels of depression (P < 0.001), anxiety (P < 0.001), and post-traumatic stress symptoms (P < 0.001). A gender effect was observed in the score of "Perceived Helplessness", the subscale of PSS-10, with female patients showing higher scores compared to male patients (Z = 2.56, P = 0.010), female (Z = 2.37, P = 0.018) and male controls (Z = 2.87, P = 0.004). Levels of CRP, a peripheral inflammatory indicator, correlated positively with the PHQ-9 total score (R = 0.37, P = 0.003, Spearman's correlation) of patients who presented symptoms of depression. Moreover, the change of CRP level from baseline inversely correlated with the PHQ-9 total score (R = -0.31, P = 0.002), indicative of improvement of depression symptoms. Qualitative analysis revealed similar results with respect to patient reports of negative feelings, including fear, guilt, and helplessness. Stigma and uncertainty of viral disease progression were two main concerns expressed by COVID-19 patients. Our results indicate that significant psychological distress was experienced by hospitalized COVID-19 patients and that levels of depressive features may be related to the inflammation markers in these patients. Thus, we recommend that necessary measures should be provided to address depression and other psychiatric symptoms for COVID-19 patients and attention should be paid to patient perceived stigma and coping strategies when delivering psychological interventions.
Assuntos
Ansiedade/psicologia , Proteína C-Reativa/imunologia , Infecções por Coronavirus/psicologia , Depressão/psicologia , Inflamação/imunologia , Pneumonia Viral/psicologia , Angústia Psicológica , Quarentena/psicologia , Estresse Psicológico/psicologia , Adulto , Idoso , Ansiedade/imunologia , Betacoronavirus , Sedimentação Sanguínea , COVID-19 , Estudos de Casos e Controles , Infecções por Coronavirus/imunologia , Estudos Transversais , Depressão/imunologia , Feminino , Hospitalização , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Questionário de Saúde do Paciente , Pneumonia Viral/imunologia , Pró-Calcitonina/imunologia , SARS-CoV-2 , Fatores Sexuais , Transtornos de Estresse Pós-Traumáticos/imunologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Estresse Psicológico/imunologiaRESUMO
OBJECTIVE: To investigate the possible association between salivary CRP, IL-1ß, and IL-6 levels, depression/anxiety and migraine, and tension type headache (TTH) in saliva of these patients. METHOD: A longitudinal prospective study was conducted on 30 migraineurs, 30 TTH patients, and 30 age-matched healthy controls. Anxiety and depression were measured by using the Hamilton Anxiety Rating Scale (HAM-A), and the Beck Depression Inventory (BDI). Salivary IL-6, IL-1ß, and CRP were collected in distinct time points as A: headache-free period, B: during headache, C: 1 day after headache attack, and measured by using ELISA kits. RESULTS: No significant differences were found in time variation of CRP, IL-1ß, and IL-6 levels between migraine and TTH (p > 0.05). IL1-ß had the highest discriminative value (area under the curve = 0.924, p value < 0.001), and then CRP (area under the curve = 0.763, p value < 0.001) and IL-6 (area under the curve = 0.537, p value = 0.58). CRP and IL-6 were negatively correlated with HAM-A and BDI scores. CONCLUSION: IL1-ß had the highest discriminative value between headache patients and controls compared with CRP and IL-6. CRP and IL-6 were correlated with lower symptom scores of anxiety and depression prior or immediately after the headache period in patients groups.
Assuntos
Ansiedade , Proteína C-Reativa/imunologia , Depressão , Inflamação , Interleucina-1beta/imunologia , Interleucina-6/imunologia , Transtornos de Enxaqueca , Sistema de Registros , Cefaleia do Tipo Tensional , Adulto , Ansiedade/epidemiologia , Ansiedade/imunologia , Ansiedade/metabolismo , Proteína C-Reativa/metabolismo , Comorbidade , Depressão/epidemiologia , Depressão/imunologia , Depressão/metabolismo , Feminino , Humanos , Inflamação/epidemiologia , Inflamação/imunologia , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/imunologia , Transtornos de Enxaqueca/metabolismo , Saliva/metabolismo , Cefaleia do Tipo Tensional/epidemiologia , Cefaleia do Tipo Tensional/imunologia , Cefaleia do Tipo Tensional/metabolismo , Fatores de TempoRESUMO
Immune dysregulation, specifically of inflammatory processes, has been linked to behavioral symptoms of depression in both human and rodent studies. Here, we evaluated the antidepressant effects of immunization with altered peptide ligands of myelin basic protein (MBP)-MBP87-99[A91, A96], MBP87-99[A91], and MBP87-99[R91, A96]-in different models of depression and examined the mechanism by which these peptides protect against stress-induced depression. We found that a single dose of subcutaneously administered MBP87-99[A91, A96] produced antidepressant-like effects by decreasing immobility in the forced swim test and by reducing the escape latency and escape failures in the learned helplessness paradigm. Moreover, immunization with MBP87-99[A91, A96] prevented and reversed depressive-like and anxiety-like behaviors that were induced by chronic unpredictable stress (CUS). However, MBP87-99[R91, A96] tended to aggravate CUS-induced anxiety-like behavior. Chronic stress increased the production of peripheral and central proinflammatory cytokines and induced the activation of microglia in the prelimbic cortex (PrL), which was blocked by MBP87-99[A91, A96]. Immunization with MBP-derived altered peptide ligands also rescued chronic stress-induced deficits in p11, phosphorylated cyclic adenosine monophosphate response element binding protein, and brain-derived neurotrophic factor expression. Moreover, microinjections of recombinant proinflammatory cytokines and the knockdown of p11 in the PrL blunted the antidepressant-like behavioral response to MBP87-99[A91, A96]. Altogether, these findings indicate that immunization with altered MBP peptide produces prolonged antidepressant-like effects in rats, and the behavioral response is mediated by inflammatory factors (particularly interleukin-6), and p11 signaling in the PrL. Immune-neural interactions may impact central nervous system function and alter an individual's response to stress.
Assuntos
Antidepressivos/química , Antidepressivos/imunologia , Depressão/imunologia , Depressão/terapia , Imunização , Proteína Básica da Mielina/química , Proteína Básica da Mielina/imunologia , Animais , Antidepressivos/uso terapêutico , Ansiedade/tratamento farmacológico , Ansiedade/etiologia , Ansiedade/imunologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/tratamento farmacológico , Depressão/etiologia , Modelos Animais de Doenças , Proteína Básica da Mielina/administração & dosagem , Proteína Básica da Mielina/uso terapêutico , Ratos , Estresse Psicológico/complicações , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/imunologiaRESUMO
Physical or mental stress leads to neuroplasticity in the brain and increases the risk of depression and anxiety. Stress exposure causes the dysfunction of peripheral T lymphocytes. However, the pathological role and underlying regulatory mechanism of peripheral T lymphocytes in mood disorders have not been well established. Here, we show that the lack of CD4+ T cells protects mice from stress-induced anxiety-like behavior. Physical stress-induced leukotriene B4 triggers severe mitochondrial fission in CD4+ T cells, which further leads to a variety of behavioral abnormalities including anxiety, depression, and social disorders. Metabolomic profiles and single-cell transcriptome reveal that CD4+ T cell-derived xanthine acts on oligodendrocytes in the left amygdala via adenosine receptor A1. Mitochondrial fission promotes the de novo synthesis of purine via interferon regulatory factor 1 accumulation in CD4+ T cells. Our study implicates a critical link between a purine metabolic disorder in CD4+ T cells and stress-driven anxiety-like behavior.
Assuntos
Ansiedade/metabolismo , Comportamento Animal/fisiologia , Encefalopatias Metabólicas/metabolismo , Estresse Psicológico/metabolismo , Tonsila do Cerebelo/metabolismo , Tonsila do Cerebelo/patologia , Animais , Ansiedade/genética , Ansiedade/imunologia , Ansiedade/fisiopatologia , Encefalopatias Metabólicas/genética , Encefalopatias Metabólicas/fisiopatologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Modelos Animais de Doenças , Humanos , Camundongos , Dinâmica Mitocondrial/genética , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Análise de Célula Única , Estresse Psicológico/genética , Estresse Psicológico/fisiopatologia , Transcriptoma/genética , Xantina/metabolismoRESUMO
Psychological distress has long been suspected to influence cancer incidence and mortality. It remains largely unknown whether and how stress affects the efficacy of anticancer therapies. We observed that social defeat caused anxiety-like behaviors in mice and dampened therapeutic responses against carcinogen-induced neoplasias and transplantable tumors. Stress elevated plasma corticosterone and upregulated the expression of glucocorticoid-inducible factor Tsc22d3, which blocked type I interferon (IFN) responses in dendritic cell (DC) and IFN-γ+ T cell activation. Similarly, close correlations were discovered among plasma cortisol levels, TSC22D3 expression in circulating leukocytes and negative mood in patients with cancer. In murine models, exogenous glucocorticoid injection, or enforced expression of Tsc22d3 in DC was sufficient to abolish therapeutic control of tumors. Administration of a glucocorticoid receptor antagonist or DC-specific Tsc22d3 deletion reversed the negative impact of stress or glucocorticoid supplementation on therapeutic outcomes. Altogether, these results indicate that stress-induced glucocorticoid surge and Tsc22d3 upregulation can subvert therapy-induced anticancer immunosurveillance.
Assuntos
Imunidade Celular , Neoplasias/imunologia , Estresse Psicológico/imunologia , Fatores de Transcrição/genética , Animais , Ansiedade/sangue , Ansiedade/induzido quimicamente , Ansiedade/imunologia , Ansiedade/psicologia , Comportamento Animal/fisiologia , Carcinógenos/toxicidade , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/psicologia , Corticosterona/sangue , Células Dendríticas/transplante , Regulação Neoplásica da Expressão Gênica , Glucocorticoides/farmacologia , Humanos , Hidrocortisona/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/psicologia , Ativação Linfocitária/genética , Camundongos , Monitorização Imunológica/métodos , Neoplasias/induzido quimicamente , Neoplasias/genética , Neoplasias/psicologia , Receptores de Glucocorticoides/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/psicologia , Estresse Psicológico/induzido quimicamente , Estresse Psicológico/genética , Estresse Psicológico/terapia , Fatores de Transcrição/imunologiaRESUMO
BACKGROUND: Different psychiatric diagnostic groups have been reported to have cytokine levels deviating from healthy controls. In acute clinical settings however, the specific challenging symptoms and signs are more important than a diagnostic group. Thus, exploration of cytokines and immune activity and their role in specific symptoms is important. Reports in this field so far are sparse. OBJECTIVE: In the present study, we aimed to examine the association between immune activity measured as levels of cytokines and agitation (independent of diagnostic group) in patients admitted to an acute psychiatric inpatient department. METHODS: A total of 316 patients admitted to an acute psychiatric inpatient department were included. Thirty-nine patients with psychosis were subject to subgroup analyses. Agitation was assessed by the Positive and Negative Syndrome Scale, Excitement Component (PANSS-EC). Based on PANNS-EC patients were stratified into two groups: 67 agitated patients and 249 non-agitated patients. Serum concentrations of the following immune markers were measured: interleukin (IL) -1ß, IL-4, IL-6, IL-10, tumor necrosis factor (TNF) -α, interferon (IFN) -γ and transforming growth factor (TGF) -ß. RESULTS: Serum levels of TNF-α were significantly higher in patients with agitation compared to those without, both when all patients were included in the analyses (p = 0.004) and in the psychosis group (p = 0.027). After correcting for multiple testing, only the findings in the total population remained significant. CONCLUSIONS: Our findings suggest an association between TNF-α and agitation in an acute psychiatric population. A similar trend was reproduced to the psychosis subgroup. This suggests that agitation might be an independent entity associated with cytokines across different diagnostic groups.
Assuntos
Ansiedade/imunologia , Transtornos Psicóticos/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Ansiedade/psicologia , Biomarcadores/sangue , Estudos Transversais , Citocinas/análise , Citocinas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Noruega , Agitação Psicomotora/diagnóstico , Agitação Psicomotora/metabolismo , Transtornos Psicóticos/psicologia , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUND: Hyperactivation of innate immunity has been implicated in the etiology of mood disorders, including major depressive disorder (MDD). Mesenchymal stromal cells (MSCs) have demonstrated potent immunomodulatory capabilities in the context of chronic inflammatory disease and injury but have yet to be evaluated in stress-based preclinical models of MDD. We sought to test the ability of intravenous MSCs to modulate innate immune activation and behavioral patterns associated with repeated social defeat (RSD). METHODS: Murine RSD-induced innate immune activation as well as depressive and anxiety-like behaviors were assessed in unstressed, RSD, and RSD + human MSC groups. Biodistribution and fate studies were performed to inform potential mechanisms of action. RESULTS: MSCs reduced stress-induced circulating proinflammatory cytokines, monocytes, neuroinflammation, and depressive and anxiety-like behaviors. Biodistribution analyses indicated that infused MSCs distributed within peripheral organs without homing to the brain. Murine neutrophils targeted MSCs in the lungs within hours of administration. MSCs and recipient neutrophils were cleared by recipient macrophages promoting a switch toward a regulatory phenotype and systemic resolution of inflammation. CONCLUSIONS: Peripheral delivery of MSCs modulates central nervous system inflammatory processes and aberrant behavioral patterns in a stress-based rodent model of MDD and anxiety. Recent studies suggest that host immune cell-mediated phagocytosis of MSCs in vivo can trigger an immunomodulatory cascade, resulting in resolution of inflammation. Our data suggest that similar mechanisms may protect distal organs, including the brain, from systemic, stress-induced proinflammatory spikes and may uncover unexpected targets in the periphery for novel or adjunct treatment for a subset of patients with MDD.
Assuntos
Comportamento , Proliferação de Células , Inflamação/imunologia , Macrófagos/imunologia , Células-Tronco Mesenquimais/imunologia , Animais , Ansiedade/imunologia , Biomarcadores , Células Cultivadas , Citocinas/imunologia , Depressão/imunologia , Modelos Animais de Doenças , Humanos , Imunidade Inata , Camundongos , Monócitos/imunologia , Distribuição TecidualRESUMO
Current evidence indicates that depression is accompanied by the activation of inflammatory response and oxidative stress. Protein arginine methyltransferase 1 (PRMT1) is a histone methyltransferase that methylates Arg3 on histone H4, playing crucial role in regulating various pathological processes. In the study, we attempted to explore the effects of PRMT1 on animal model with depression through a single administration of lipopolysaccharide (LPS). Our results indicated that PRMT1 knockout (PRMT1-/-) improved LPS-induced anxiety- and depressive-like behavior, along with up-regulated expression levels of brain-derived neurotrophic factor (BDNF) and PSD-95. Furthermore, PRMT1 deficiency significantly improved LPS-induced changes in dendritic spine density in the areas of prefrontal cortex (PFC), CA3 and dentate gyrus (DG), and nucleus accumbens (NAc). In addition, PRMT1 deletion ameliorated the neuroinflammatory responses, as evidenced by the reduced expression of interleukin 1ß (IL-1ß) and tumor necrosis factor (TNF)-α, which might be through repressing nuclear factor-κB (NF-κB) signaling. Moreover, oxidative stress induced by LPS was alleviated by PRMT1 knockout in hippocampus of mice at least partly via promoting Nrf-2 expressions. The anti-depressant effects of PRMT1 inhibition were verified in LPS-incubated astrocytes. Importantly, we found that PRMT1 knockout-alleviated inflammation and oxidative stress triggered by LPS were significantly recovered by the suppression of Nrf-2. Therefore, Nrf-2 was markedly involved in PRMT1-regulated depression-like behavior. Taken together, the results indicated that PRMT1 might be an important therapeutic target for developing effective treatment to prevent depressive-like behavior.
Assuntos
Depressão/genética , Inflamação/genética , Fator 2 Relacionado a NF-E2/genética , Proteína-Arginina N-Metiltransferases/genética , Animais , Ansiedade/genética , Ansiedade/imunologia , Ansiedade/patologia , Depressão/imunologia , Depressão/patologia , Deleção de Genes , Inflamação/imunologia , Inflamação/patologia , Lipopolissacarídeos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 2 Relacionado a NF-E2/imunologia , Estresse Oxidativo , Proteína-Arginina N-Metiltransferases/imunologia , Regulação para CimaRESUMO
Patients with diabetes mellitus (DM) showed an increased risk of anxiety. High anxiety levels are also shown to increase stress of diabetic patients, which may contribute to poor clinical outcomes. The mechanisms underlying the development of anxiety disorders in diabetic patients remain unknown. As a result, there are no available treatments yet. Here, we tested the hypothesis that glial cells in the hippocampal area of DM mice might be responsible for their anxiety-like behaviors. Furthermore, we postulated that treatment with antidepressant, fluoxetine, could reduce anxiety behaviors and prevent the dysregulation of glial cells (oligodendrocyte and astrocyte) in DM mice. Diabetic mice were administered a single injection of streptozotocin (STZ), followed by treatment with fluoxetine. Mice were then tested on Y maze, open field, dark and light transition, and elevated plus maze tests to measure the status of anxiety and cognition. After completing these behavioral tests, mice were sacrificed and western blot was used to detect the oligodendrocyte and astrocyte maker proteins in hippocampal tissues. Emphasis was directed towards adult oligodendrocyte precursor cells (OPCs) and their marker protein to measure their proliferation and differentiation. We found that fluoxetine could effectively mitigate the level of anxiety and attenuate the cognitive dysfunction in diabetic mice. Meanwhile, fluoxetine inhibited astrocyte activation in mice exposed to STZ, prevented the loss of myelin basic protein (MBP), and affected the function of OPCs in these diabetic mice. The results suggested that the changes of these glial cells in the brains of diabetic mice might be related to the high anxiety levels and cognitive deficit in DM mice. Fluoxetine could ameliorate the high anxiety level and prevent cognitive deficit via inhibiting astrocyte activation and repairing the oligodendrocyte damage.
Assuntos
Ansiedade/tratamento farmacológico , Diabetes Mellitus Experimental/tratamento farmacológico , Fluoxetina/uso terapêutico , Inflamação/tratamento farmacológico , Animais , Antidepressivos/uso terapêutico , Ansiedade/imunologia , Western Blotting , Diabetes Mellitus Experimental/imunologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Proteína Glial Fibrilar Ácida/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Inflamação/imunologia , Interleucina-6/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BLRESUMO
This study compared the abilities of γ-[Glu]n-Trp (EW) and whey protein hydrolysate (WPH) with a high ratio of Trp : 5 large neutral amino acids (5LNAAs) to reverse chronic restraint stress-corticosterone injection induced anxiety/depression-like behaviors in C57BL/6 male mice. EW was synthesized using l-glutaminase from Bacillus amyloliquefaciens. Acid protease, trypsin, pancreatin or flavorzyme was used to produce WPHs. The WPH with the highest Trp/5LNAAs ratio (17.38%; by trypsin) was selected for animal trials. EW (dose 2.0, 5.0 or 10.0 mg kg-1 d-1) and WPH (dose 0.5, 1.0 or 2.0 mg g-1 d-1) reversed behavioral dysfunctions, suppressed serum inflammatory cytokines (TNF-α, IL-6, IL-1ß and IFN-γ), and reduced the activity of indoleamine 2,3-dioxygenase (key rate-limiting enzyme of the kynurenine pathway) while increasing the activity of tryptophan hydroxylase (key rate-limiting enzyme of the serotonin pathway) in the hypothalamus, hippocampus and prefrontal cortex, with EW acting more effectively. EW could also increase body weight gain and might act more effectively via the kynurenine pathway. These findings are of significance to promote the future practical application of kokumi γ-[Glu]n-Trp peptides.
Assuntos
Anti-Inflamatórios/administração & dosagem , Ansiedade/tratamento farmacológico , Depressão/tratamento farmacológico , Oligopeptídeos/administração & dosagem , Animais , Ansiedade/genética , Ansiedade/imunologia , Ansiedade/psicologia , Comportamento Animal/efeitos dos fármacos , Depressão/genética , Depressão/imunologia , Depressão/psicologia , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/imunologia , Humanos , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/imunologia , Triptofano/química , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Proteínas do Soro do Leite/químicaRESUMO
RATIONALE: Mycobacterium vaccae (NCTC 11659) is an environmental saprophytic bacterium with anti-inflammatory, immunoregulatory, and stress resilience properties. Previous studies have shown that whole, heat-killed preparations of M. vaccae prevent allergic airway inflammation in a murine model of allergic asthma. Recent studies also demonstrate that immunization with M. vaccae prevents stress-induced exaggeration of proinflammatory cytokine secretion from mesenteric lymph node cells stimulated ex vivo, prevents stress-induced exaggeration of chemically induced colitis in a model of inflammatory bowel disease, and prevents stress-induced anxiety-like defensive behavioral responses. Furthermore, immunization with M. vaccae induces anti-inflammatory responses in the brain and prevents stress-induced exaggeration of microglial priming. However, the molecular mechanisms underlying anti-inflammatory effects of M. vaccae are not known. OBJECTIVES: Our objective was to identify and characterize novel anti-inflammatory molecules from M. vaccae NCTC 11659. METHODS: We have purified and identified a unique anti-inflammatory triglyceride, 1,2,3-tri [Z-10-hexadecenoyl] glycerol, from M. vaccae and evaluated its effects in freshly isolated murine peritoneal macrophages. RESULTS: The free fatty acid form of 1,2,3-tri [Z-10-hexadecenoyl] glycerol, 10(Z)-hexadecenoic acid, decreased lipopolysaccharide-stimulated secretion of the proinflammatory cytokine IL-6 ex vivo. Meanwhile, next-generation RNA sequencing revealed that pretreatment with 10(Z)-hexadecenoic acid upregulated genes associated with peroxisome proliferator-activated receptor alpha (PPARα) signaling in lipopolysaccharide-stimulated macrophages, in association with a broad transcriptional repression of inflammatory markers. We confirmed using luciferase-based transfection assays that 10(Z)-hexadecenoic acid activated PPARα signaling, but not PPARγ, PPARδ, or retinoic acid receptor (RAR) α signaling. The effects of 10(Z)-hexadecenoic acid on lipopolysaccharide-stimulated secretion of IL-6 were prevented by PPARα antagonists and absent in PPARα-deficient mice. CONCLUSION: Future studies should evaluate the effects of 10(Z)-hexadecenoic acid on stress-induced exaggeration of peripheral inflammatory signaling, central neuroinflammatory signaling, and anxiety- and fear-related defensive behavioral responses.
Assuntos
Anti-Inflamatórios/imunologia , Anti-Inflamatórios/isolamento & purificação , Mycobacterium/imunologia , Mycobacterium/isolamento & purificação , Estresse Psicológico/imunologia , Estresse Psicológico/prevenção & controle , Animais , Ansiedade/induzido quimicamente , Ansiedade/imunologia , Ansiedade/prevenção & controle , Colite/induzido quimicamente , Colite/imunologia , Colite/prevenção & controle , Medo/efeitos dos fármacos , Medo/fisiologia , Inflamação/imunologia , Inflamação/prevenção & controle , Lipopolissacarídeos/toxicidade , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/imunologia , Microbiologia do Solo , Estresse Psicológico/induzido quimicamenteRESUMO
BACKGROUND: Controversial findings regarding the association between pro-inflammatory cytokines and depression have been reported in pregnant subjects. Scarce data about anxiety and its relationships with cytokines are available in pregnant women. To understand the association between anxiety and cytokines during pregnancy, we conducted the present study in women with or without depression. METHODS: Women exhibiting severe depression (SD) and severe anxiety (SA) during the 3rd trimester of pregnancy (n = 139) and control subjects exhibiting neither depression nor anxiety (n = 40) were assessed through the Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HARS). Serum cytokines were measured by a multiplex bead-based assay. Correlation tests were used to analyze the data and comparisons between groups were performed. A general linear model of analysis of variance was constructed using the group as a dependent variable, interleukin concentrations as independent variables, and HDRS/HARS scores and gestational weeks as covariables. RESULTS: The highest levels of Th1- (IL-6, TNF-α, IL-2, IFN-γ), Th17- (IL-17A, IL-22), and Th2- (IL-9, IL-10, and IL-13) related cytokines were observed in women with SD + SA. The SA group showed higher concentrations of Th1- (IL-6, TNF-α, IL-2, IFN-γ) and Th2- (IL-4, and IL-10) related cytokines than the controls. Positive correlations were found between HDRS and IL-2, IL-6, and TNF-α in the SA group (p < 0.03), and between HDRS and Th1- (IL-2, IL-6, TNF-α), Th2- (IL-9, IL-10, IL-13) and Th17- (IL-17A) cytokines (p < 0.05) in the SD + SA group. After controlling the correlation analysis by gestational weeks, the correlations that remained significant were: HDRS and IL-2, IL-6, IL-9, and IL-17A in the SD + SA group (p < 0.03). HARS scores correlated with IL-17A in the SA group and with IL-17A, IL-17F, and IL-2 in the SD + SA group (p < 0.02). The linear model of analysis of variance showed that HDRS and HARS scores influenced cytokine concentrations; only IL-6 and TNF-α could be explained by the group. CONCLUSIONS: We found that the cytokine profiles differ when comparing pregnant subjects exhibiting SA with comorbid SD against those showing only SA without depression.
Assuntos
Ansiedade/imunologia , Depressão/imunologia , Complicações na Gravidez/imunologia , Adulto , Transtornos de Ansiedade , Estudos de Casos e Controles , Citocinas/sangue , Feminino , Humanos , Interleucina-10/sangue , Interleucina-17/sangue , Gravidez , Gestantes , Fator de Necrose Tumoral alfa/sangue , Adulto JovemRESUMO
Fatigue is a common and distressing symptom in both patients with cancer and cancer survivors. There is substantial variation in the severity and persistence of cancer-related fatigue that may be driven by individual differences in host factors, including characteristics that predate the cancer experience as well as responses to cancer and its treatment. This review examines biobehavioral risk factors linked to fatigue and the mechanisms through which they influence fatigue across the cancer continuum, with a focus on neuro-immune processes. Among psychosocial risk factors, childhood adversity is a strong and consistent predictor of cancer-related fatigue; other risk factors include history of depression, catastrophizing, lack of physical activity, and sleep disturbance, with compelling preliminary evidence for loneliness and trait anxiety. Among biologic systems, initial work suggests that alterations in immune, neuroendocrine, and neural processes are associated with fatigue. The identification of key risk factors and underlying mechanisms is critical for the development and deployment of targeted interventions to reduce the burden of fatigue in the growing population of cancer survivors. Given the multidimensional nature of fatigue, interventions that influence multiple systems may be most effective.
Assuntos
Comportamento/fisiologia , Fadiga/etiologia , Neoplasias/complicações , Neuroimunomodulação/fisiologia , Ansiedade/etiologia , Ansiedade/imunologia , Ansiedade/psicologia , Sobreviventes de Câncer/psicologia , Sobreviventes de Câncer/estatística & dados numéricos , Depressão/etiologia , Depressão/imunologia , Depressão/psicologia , Fadiga/epidemiologia , Humanos , Neoplasias/epidemiologia , Qualidade de Vida/psicologia , Fatores de RiscoRESUMO
Traumatic spinal cord injury (SCI) promotes long-term disability that affects mobility and functional independence. The spinal cord inflammatory response after the initial mechanical insult substantially impacts locomotor impairment and development of neuropsychiatric disorders, including anxiety and depression. However, these psychiatric events are scarcely investigated in females. This study investigated the anxiety/depression-like behaviours and inflammatory responses related to the production/release of pro- and anti-inflammatory cytokines in female adult Wistar rats submitted to severe clip-compression SCI. Data showed that SCI impaired the locomotor performance assessment by the BBB scale, but did not alter exploratory activity in open-field test. Animals' locomotor impairment was associated with anxious and depressive-like behaviours characterised by a decreased amount of time in the open arms of the elevated plus-maze test, and the motivational reduction of social interaction and anhedonia assessed by social exploration and sucrose preference tests. By contrast, SCI decreased the immobility time in the forced swimming test. Moreover, SCI caused a significant increase in local and systemic proinflammatory cytokines (TNF-α, INF-γ, IL-1ß, and IL-6) and a reduction in the anti-inflammatory cytokine IL-10. Finally, there were significant negative correlations between depression-like behaviour, but not anxiety, and increased plasma concentrations of TNF-α, IL-1ß, IL-6, and INF-γ. Additionally, the laminectomy procedure provoked the inflammatory response associated with reduced sucrose intake in Sham animals, although less expressively than in the SCI group. Collectively, these results indicate that SCI by clip-compression in female rats promotes a neuropsychiatric-like profile associated with an imbalance in the production/release of pro- and anti-inflammatory cytokines.
Assuntos
Ansiedade/imunologia , Depressão/imunologia , Traumatismos da Medula Espinal/psicologia , Animais , Transtornos de Ansiedade/complicações , Comportamento Animal , Citocinas , Transtorno Depressivo/complicações , Modelos Animais de Doenças , Feminino , Inflamação/complicações , Ratos , Ratos Wistar , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/imunologia , Fator de Necrose Tumoral alfaRESUMO
OBJECTIVE: To evaluate the relationship between the inflammatory profile and mood states in the different phases of the menstrual cycle in soccer players with and without premenstrual syndrome (PMS). METHODS: Data on the menstrual cycle and mood states were collected using the Daily Symptom Report and the Brunel Mood Scale. Cytokine and stress hormone concentrations were measured in urine by flow cytometry before and after a game in the luteal phase and in the follicular phase of one menstrual cycle. RESULTS: In all, 59.6% of the athletes had PMS. The PMS group showed higher concentrations of interleukin (IL)-1ß, IL-6, and IL-8 than the athletes without PMS. After the game, IL-6 decreased in the follicular phase and the luteal phase. The tumor necrosis factor-α levels were higher in the group without PMS during the post-game follicular phase than before the game. In the PMS group, tension was higher in the follicular phase before the game and depression was higher in the pre-game luteal phase than in the group without PMS. The PMS group also presented a negative correlation between depression and IL-10 levels in the pre-game follicular phase. Finally, in the pre-game luteal phase were found positive correlations between growth hormone and IL-10. CONCLUSION: PMS influences the inflammatory condition related to mood states and stress hormones in female soccer players.