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1.
Nutrients ; 13(7)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34371931

RESUMO

The purpose of this study was to examine the independent and joint associations of acid-producing diets and depressive symptoms with physical health among breast cancer survivors. We studied a cohort of 2944 early stage breast cancer survivors who provided dietary, physical health, demographic, and lifestyle information at baseline, year 1, and year 4. We assessed the intakes of acid-producing diets via two commonly used dietary acid load scores: potential renal acid load (PRAL) and net endogenous acid production (NEAP). Physical health was measured using the Rand 36-Item Short Form Health Survey (SF-36), consisting of physical functioning, role limitation due to physical function, bodily pain, general health, and overall physical health subscales. Increased dietary acid load and depression were each independently and significantly associated with reduced physical health subscales and overall physical health. Further, dietary acid load and depression were jointly associated with worse physical health. For instance, depressed women with dietary acid load higher than median reported 2.75 times the risk (odds ratio = 2.75; 95% confidence interval: 2.18-3.47) of reduced physical function and 3.10 times the risk of poor physical health (odds ratio = 3.10; 95% confidence interval: 2.53-3.80) compared to non-depressed women with dietary acid load lower than median. Our results highlight the need of controlling acid-producing diets and the access of mental care for breast cancer survivors.


Assuntos
Ácidos/efeitos adversos , Afeto , Neoplasias da Mama/terapia , Sobreviventes de Câncer/psicologia , Depressão/complicações , Dieta/efeitos adversos , Saúde Mental , Ácidos/metabolismo , Adulto , Depressão/diagnóstico , Depressão/psicologia , Feminino , Nível de Saúde , Humanos , Concentração de Íons de Hidrogênio , Pessoa de Meia-Idade , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Fatores de Tempo
2.
J Int Neuropsychol Soc ; 27(6): 661-672, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34261550

RESUMO

OBJECTIVE: Recent cannabis exposure has been associated with lower rates of neurocognitive impairment in people with HIV (PWH). Cannabis's anti-inflammatory properties may underlie this relationship by reducing chronic neuroinflammation in PWH. This study examined relations between cannabis use and inflammatory biomarkers in cerebrospinal fluid (CSF) and plasma, and cognitive correlates of these biomarkers within a community-based sample of PWH. METHODS: 263 individuals were categorized into four groups: HIV- non-cannabis users (n = 65), HIV+ non-cannabis users (n = 105), HIV+ moderate cannabis users (n = 62), and HIV+ daily cannabis users (n = 31). Differences in pro-inflammatory biomarkers (IL-6, MCP-1/CCL2, IP-10/CXCL10, sCD14, sTNFR-II, TNF-α) by study group were determined by Kruskal-Wallis tests. Multivariable linear regressions examined relationships between biomarkers and seven cognitive domains, adjusting for age, sex/gender, race, education, and current CD4 count. RESULTS: HIV+ daily cannabis users showed lower MCP-1 and IP-10 levels in CSF compared to HIV+ non-cannabis users (p = .015; p = .039) and were similar to HIV- non-cannabis users. Plasma biomarkers showed no differences by cannabis use. Among PWH, lower CSF MCP-1 and lower CSF IP-10 were associated with better learning performance (all ps < .05). CONCLUSIONS: Current daily cannabis use was associated with lower levels of pro-inflammatory chemokines implicated in HIV pathogenesis and these chemokines were linked to the cognitive domain of learning which is commonly impaired in PWH. Cannabinoid-related reductions of MCP-1 and IP-10, if confirmed, suggest a role for medicinal cannabis in the mitigation of persistent inflammation and cognitive impacts of HIV.

3.
Neurosci Biobehav Rev ; 125: 517-534, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33639178

RESUMO

Obsessive-compulsive disorder (OCD) is disabling and often treatment-refractory. Host immunity and gut microbiota have bidirectional communication with each other and with the brain. Perturbations to this axis have been implicated in neuropsychiatric disorders, but immune-microbiome signaling in OCD is relatively underexplored. We review support for further pursuing such investigations in OCD, including: 1) gut microbiota has been associated with OCD, but causal pathogenic mechanisms remain unclear; 2) early environmental risk factors for OCD overlap with critical periods of immune-microbiome development; 3) OCD is associated with increased risk of immune-mediated disorders and changes in immune parameters, which are separately associated with the microbiome; and 4) gut microbiome manipulations in animal models are associated with changes in immunity and some obsessive-compulsive symptoms. Theoretical pathogenic mechanisms could include microbiota programming of cytokine production, promotion of expansion and trafficking of peripheral immune cells to the CNS, and regulation of microglial function. Immune-microbiome signaling in OCD requires further exploration, and may offer novel insights into pathogenic mechanisms and potential treatment targets for this disabling disorder.


Assuntos
Microbioma Gastrointestinal , Microbiota , Transtorno Obsessivo-Compulsivo , Animais , Encéfalo
4.
J Acquir Immune Defic Syndr ; 87(2): 851-859, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33587499

RESUMO

BACKGROUND: Depression and neurocognitive impairment are highly prevalent among persons living with HIV and associated with poorer clinical outcomes; however, longitudinal studies of depression-neurocognition relationships in youth living with HIV (YLWH), and the role of antiretroviral therapy (ART), are lacking. This study tested whether (1) depressive symptomatology, across somatic, cognitive, and affective symptom domains, improved with ART and (2) more severe depressive symptoms at baseline were associated with poorer neurocognitive function and poorer HIV suppression. SETTING: Data were collected from 181 YLWH (18-24 years) who were treatment-naive, a subset of whom (n = 116) initiated ART. METHODS: Participants were categorized into elevated (DS) or nonelevated (non-DS) depressive symptom groups at entry (Beck Depression Inventory-II ≥14) and followed for 36 months. Neurocognition (5-domain battery) and depressive symptoms were repeatedly assessed. Longitudinal models examined depressive symptomatology, neurocognition, and odds of HIV nonsuppression by group. RESULTS: Greater improvements in depressive symptoms were observed in the DS group over 36 months [beta = -0.14, (-0.24 to -0.03)], particularly within cognitive and affective domains. Verbal learning performance increased in the DS group [beta = 0.13, (0.01 to 0.24)], whereas psychomotor function improved somewhat in the non-DS group [beta = -0.10, (-0.22 to 0.00)]. Adjusted for ART adherence, odds of HIV nonsuppression did not significantly differ by group [odds ratio = 0.22, (0.04 to 1.23)]; however, greater somatic symptoms at study entry were associated with an increased risk of nonsuppression over time [odds ratio = 2.33 (1.07 to 5.68)]. CONCLUSION: Depressive symptoms were associated with differential neurocognitive trajectories, and somatic depressive symptoms at baseline may predict poorer subsequent HIV suppression. Identifying and treating depressive symptoms at ART initiation may benefit neurocognitive and clinical outcomes in YLWH.


Assuntos
Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/virologia , Depressão/epidemiologia , Depressão/virologia , Infecções por HIV/psicologia , Adolescente , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Disfunção Cognitiva/psicologia , Depressão/psicologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Humanos , Estudos Longitudinais , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , RNA Viral/sangue , Carga Viral/efeitos dos fármacos , Adulto Jovem
6.
Brain Behav Immun ; 87: 34-39, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32298803

RESUMO

The coronavirus disease 19 (COVID-19) pandemic is a significant psychological stressor in addition to its tremendous impact on every facet of individuals' lives and organizations in virtually all social and economic sectors worldwide. Fear of illness and uncertainty about the future precipitate anxiety- and stress-related disorders, and several groups have rightfully called for the creation and dissemination of robust mental health screening and treatment programs for the general public and front-line healthcare workers. However, in addition to pandemic-associated psychological distress, the direct effects of the virus itself (several acute respiratory syndrome coronavirus; SARS-CoV-2), and the subsequent host immunologic response, on the human central nervous system (CNS) and related outcomes are unknown. We discuss currently available evidence of COVID-19 related neuropsychiatric sequelae while drawing parallels to past viral pandemic-related outcomes. Past pandemics have demonstrated that diverse types of neuropsychiatric symptoms, such as encephalopathy, mood changes, psychosis, neuromuscular dysfunction, or demyelinating processes, may accompany acute viral infection, or may follow infection by weeks, months, or longer in recovered patients. The potential mechanisms are also discussed, including viral and immunological underpinnings. Therefore, prospective neuropsychiatric monitoring of individuals exposed to SARS-CoV-2 at various points in the life course, as well as their neuroimmune status, are needed to fully understand the long-term impact of COVID-19, and to establish a framework for integrating psychoneuroimmunology into epidemiologic studies of pandemics.


Assuntos
Infecções por Coronavirus/psicologia , Síndrome da Liberação de Citocina/psicologia , Transtornos Mentais/psicologia , Doenças do Sistema Nervoso/psicologia , Pneumonia Viral/psicologia , Doença Aguda , Ansiedade/etiologia , Ansiedade/imunologia , Ansiedade/psicologia , Translocação Bacteriana , Betacoronavirus , COVID-19 , Doença Crônica , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/terapia , Doenças Desmielinizantes/etiologia , Doenças Desmielinizantes/imunologia , Doenças Desmielinizantes/fisiopatologia , Doenças Desmielinizantes/psicologia , Depressão/etiologia , Depressão/imunologia , Depressão/psicologia , Humanos , Fatores Imunológicos/efeitos adversos , Transtornos Mentais/etiologia , Transtornos Mentais/imunologia , Saúde Mental , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/imunologia , Doenças do Sistema Nervoso/fisiopatologia , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/imunologia , Doenças Neurodegenerativas/fisiopatologia , Doenças Neurodegenerativas/psicologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Psiconeuroimunologia , Transtornos Psicóticos/etiologia , Transtornos Psicóticos/imunologia , Transtornos Psicóticos/psicologia , Saúde Pública , SARS-CoV-2 , Transtornos de Estresse Pós-Traumáticos/etiologia , Transtornos de Estresse Pós-Traumáticos/imunologia , Transtornos de Estresse Pós-Traumáticos/psicologia
7.
J Clin Med ; 9(3)2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32121255

RESUMO

BACKGROUND: Cardiopulmonary fitness and low calorie diets have been shown to reduce inflammation but few studies have been conducted in individuals with elevated blood pressure (BP) in a randomized intervention setting. Thereby, adhesion biomarkers, e.g., soluble intercellular adhesion molecule (sICAM)-3, have not been examined so far. METHODS: Sixty-eight sedentary prehypertensive and mildly hypertensive individuals (mean age ± SEM: 45 ± 1 years; mean BP: 141/84 ± 1/1 mmHg) were randomized to one of three 12-week intervention groups: cardio training and caloric reduction, cardio training alone, or wait-list control group. Plasma levels of inflammatory, adhesion and prothrombotic biomarkers were assessed. In a second step, intervention groups were combined to one sample and multivariate regression analyses were applied in order to account for exercise and diet behavior changes. RESULTS: There were no significant differences among the intervention groups. In the combined sample, greater caloric reduction was associated with a larger increase of sICAM-3 (p = 0.026) and decrease of C-reactive protein (p = 0.018) as a result of the interventions. More cardio training was associated with increases of sICAM-3 (p = 0.046) as well as interleukin-6 (p = 0.004) and a decrease of tumor necrosis factor- (p = 0.017) levels. Higher BP predicted higher plasminogen activator inhibitor (PAI)-1 (p = 0.001), and greater fitness predicted lower PAI-1 levels (p = 0.006) after the intervention. CONCLUSIONS: In prehypertensive and hypertensive patients, plasma levels of the adhesion molecule sICAM-3 and inflammatory biomarkers have different response patterns to cardio training with and without caloric reduction. Such anti-inflammatory and anti-thrombotic effects may have implications for the prevention of atherothrombotic cardiovascular disease among individuals at increased risk.

9.
Int Psychogeriatr ; 32(7): 815-825, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31647051

RESUMO

OBJECTIVES: Given the evidence of multi-parameter risk factors in shaping cognitive outcomes in aging, including sleep, inflammation, cardiometabolism, and mood disorders, multidimensional investigations of their impact on cognition are warranted. We sought to determine the extent to which self-reported sleep disturbances, metabolic syndrome (MetS) factors, cellular inflammation, depressive symptomatology, and diminished physical mobility were associated with cognitive impairment and poorer cognitive performance. DESIGN: This is a cross-sectional study. SETTING: Participants with elevated, well-controlled blood pressure were recruited from the local community for a Tai Chi and healthy-aging intervention study. PARTICIPANTS: One hundred forty-five older adults (72.7 ± 7.9 years old; 66% female), 54 (37%) with evidence of cognitive impairment (CI) based on Montreal Cognitive Assessment (MoCA) score ≤24, underwent medical, psychological, and mood assessments. MEASUREMENTS: CI and cognitive domain performance were assessed using the MoCA. Univariate correlations were computed to determine relationships between risk factors and cognitive outcomes. Bootstrapped logistic regression was used to determine significant predictors of CI risk and linear regression to explore cognitive domains affected by risk factors. RESULTS: The CI group were slower on the mobility task, satisfied more MetS criteria, and reported poorer sleep than normocognitive individuals (all p < 0.05). Multivariate logistic regression indicated that sleep disturbances, but no other risk factors, predicted increased risk of evidence of CI (OR = 2.00, 95% CI: 1.26-4.87, 99% CI: 1.08-7.48). Further examination of MoCA cognitive subdomains revealed that sleep disturbances predicted poorer executive function (ß = -0.26, 95% CI: -0.51 to -0.06, 99% CI: -0.61 to -0.02), with lesser effects on visuospatial performance (ß = -0.20, 95% CI: -0.35 to -0.02, 99% CI: -0.39 to 0.03), and memory (ß = -0.29, 95% CI: -0.66 to -0.01, 99% CI: -0.76 to 0.08). CONCLUSIONS: Our results indicate that the deleterious impact of self-reported sleep disturbances on cognitive performance was prominent over other risk factors and illustrate the importance of clinician evaluation of sleep in patients with or at risk of diminished cognitive performance. Future, longitudinal studies implementing a comprehensive neuropsychological battery and objective sleep measurement are warranted to further explore these associations.


Assuntos
Envelhecimento , Disfunção Cognitiva/complicações , Hipertensão/complicações , Transtornos do Sono-Vigília/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Memória , Testes de Estado Mental e Demência , Fatores de Risco , Autorrelato , Sono/fisiologia , Transtornos do Sono-Vigília/psicologia
10.
AIDS ; 33(15): 2363-2374, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31764101

RESUMO

OBJECTIVE: HIV-associated neurocognitive disorders persist despite early antiretroviral therapy (ART) and optimal viral suppression. We examined the relationship between immunopathogenesis driven by various pathways of immune activation and discrete neurocognitive performance domains in youth with HIV (YWH). DESIGN: Observational cross-sectional study. METHODS: YWH, ages 20-28 years, enrolled in Adolescent Medicine Trials Network 071/101 were assessed for biomarkers of macrophage, lymphocyte activation, and vascular inflammation using ELISA/multiplex assays. Standardized neurocognitive tests were performed, and demographically adjusted z-scores were combined to form indices of attention, motor, executive function, verbal, and visuospatial memory. Cross-sectional analysis of the relationship between 18 plasma inflammatory biomarkers and each neurocognitive domain was performed. Linear regression models were fit for each combination of log-transformed biomarker value and neurocognitive domain score, and were adjusted for demographics, socioeconomic status, substance use, depression, CD4 T-cell count, HIV viral load, and ART status. RESULTS: Study included 128 YWH [mean age 23.8 (SD 1.7) years, 86% men, 68% African American]. Verbal and visuospatial memory domains were most significantly impaired in the cohort (z = -1.59 and -1.0, respectively). Higher sCD14 was associated with impaired visuospatial memory, which remained robust after adjusting for other biomarkers, demographics, and HIV-associated covariates. Among biomarkers of vascular inflammation, sICAM-1 was negatively associated with verbal memory and attention, whereas sVCAM-1 was positively associated with executive function and visuospatial memory. Specific neurocognitive domains were not associated with sCD163, LPS, or CCL2 levels. CONCLUSION: Impaired visuospatial memory in YWH is associated with immune activation, as reflected by higher sCD14.


Assuntos
Disfunção Cognitiva/etiologia , Infecções por HIV/complicações , Infecções por HIV/psicologia , Receptores de Lipopolissacarídeos/sangue , Memória de Curto Prazo , Adulto , Terapia Antirretroviral de Alta Atividade , Biomarcadores/sangue , Contagem de Linfócito CD4 , Disfunção Cognitiva/diagnóstico , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Modelos Lineares , Ativação Linfocitária , Masculino , Testes de Estado Mental e Demência , Estudos Prospectivos , Porto Rico , Solubilidade , Percepção Espacial , Estados Unidos , Carga Viral , Percepção Visual , Adulto Jovem
11.
J Acquir Immune Defic Syndr ; 81(5): e148-e157, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31107306

RESUMO

OBJECTIVE: The Val allele of the Val158Met single-nucleotide polymorphism of the catechol-o-methyltransferase gene (COMT) results in faster metabolism and reduced bioavailability of dopamine (DA). Among persons living with HIV, Val carriers display neurocognitive deficits relative to Met carriers, presumably due to exacerbation of HIV-related depletion of DA. COMT may also impact neurocognition by modulating cardiometabolic function, which is often dysregulated among persons living with HIV. We examined the interaction of COMT, cardiometabolic risk, and nadir CD4 on neurocognitive impairment (NCI) among HIV+ men. METHODS: Three hundred twenty-nine HIV+ men underwent COMT genotyping and neurocognitive and neuromedical assessments. Cohort-standardized z scores for body mass index, systolic blood pressure, glucose, triglycerides, and high-density lipoprotein cholesterol were averaged to derive a cardiometabolic risk score (CMRS). NCI was defined as demographically adjusted global deficit score of ≥0.5. Logistic regression modeled NCI as a function of COMT, CMRS, and their interaction, covarying for estimated premorbid function, race/ethnicity, and HIV-specific characteristics. Follow-up analysis included the 3-way interaction of COMT, CMRS, and nadir CD4. RESULTS: Genotypes were 81 (24.6%) Met/Met, 147 (44.7%) Val/Met, and 101 (30.7%) Val/Val. COMT interacted with CMRS (P = 0.02) such that higher CMRS increased risk of NCI among Val/Val [odds ratio (OR) = 2.13, P < 0.01], but not Val/Met (OR = 0.93, P > 0.05) or Met/Met (OR = 0.92, P > 0.05) carriers. Among Val/Val, nadir CD4 moderated the effect of CMRS (P < 0.01) such that higher CMRS increased likelihood of NCI only when nadir CD4 <180. DISCUSSION: Results suggest a tripartite model by which genetically driven low DA reserve, cardiometabolic dysfunction, and historical immunosuppression synergistically enhance risk of NCI among HIV+ men, possibly due to neuroinflammation and oxidative stress.


Assuntos
Antígenos CD4 , Doenças Cardiovasculares/genética , Catecol O-Metiltransferase/genética , Infecções por HIV/complicações , Transtornos Neurocognitivos/complicações , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Doenças Cardiovasculares/metabolismo , Estudos de Coortes , Dopamina/farmacologia , Predisposição Genética para Doença , Genótipo , Humanos , Imunossupressão , Masculino , Síndrome Metabólica/genética , Pessoa de Meia-Idade , Razão de Chances , Medição de Risco , Fatores de Risco
12.
Int J Obes (Lond) ; 43(10): 2045-2056, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31089263

RESUMO

BACKGROUND: Obesity and depression are complex conditions with stronger comorbid relationships among women than men. Inflammation and cardiometabolic dysfunction are likely mechanistic candidates for increased depression risk, and their prevalence differs by sex. Whether these relationships extend to depressive symptoms is poorly understood. Therefore, we analyzed sex in associations between inflammation and metabolic syndrome (MetS) criteria on depressive symptomatology. Specifically, we examined whether sex positively moderates the relationship between depressive symptoms and inflammation among women, and whether MetS has parallel effects among men. METHODS: Depressive symptoms, MetS, and inflammation were assessed in 129 otherwise healthy adults. Depressive symptoms were assessed using Beck Depression Inventory (BDI-Ia). Monocyte inflammation regulation (BARIC) was quantified using flow cytometry measurement of TNF-α suppression by ß-agonist. Moderation effects of sex on associations between BARIC, MetS criteria, and BDI were estimated using two-way ANOVA and linear regression, adjusting for BMI, and by sex subgroup analyses. RESULTS: Obese individuals reported more depressive symptoms. Sex did not formally moderate this relationship, though BDI scores tended to differ by BMI among women, but not men, in subgroup analysis. Poorer inflammation control and higher MetS criteria were correlated with somatic depressive symptoms. Sex moderated associations between MetS criteria and somatic symptoms; among men, MetS criteria predicted somatic symptoms, not among women. Subgroup analysis further indicated that poorer inflammation control tended to be associated with higher somatic symptoms in women. CONCLUSIONS: These results indicate that obesity-related inflammation and MetS factors have sex-specific effects on depressive symptoms in a non-clinical population. Although pathophysiological mechanisms underlying sex differences remain to be elucidated, our findings suggest that distinct vulnerabilities to depressive symptoms exist between women and men, and highlight the need to consider sex as a key biological variable in obesity-depression relationships. Future clinical studies on comorbid obesity and depression should account for sex, which may optimize therapeutic strategies.


Assuntos
Proteína C-Reativa/metabolismo , Depressão/psicologia , Inflamação/psicologia , Síndrome Metabólica/psicologia , Obesidade/psicologia , Caracteres Sexuais , Adulto , California/epidemiologia , Comorbidade , Depressão/complicações , Depressão/epidemiologia , Depressão/metabolismo , Feminino , Inquéritos Epidemiológicos , Humanos , Inflamação/epidemiologia , Inflamação/etiologia , Inflamação/metabolismo , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/metabolismo , Escalas de Graduação Psiquiátrica , Adulto Jovem
13.
Brain Behav Immun ; 61: 60-68, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28011264

RESUMO

Regular exercise is shown to exert anti-inflammatory effects, yet the effects of acute exercise on cellular inflammatory responses and its mechanisms remain unclear. We tested the hypothesis that sympathoadrenergic activation during a single bout of exercise has a suppressive effect on monocytic cytokine production mediated by ß2 adrenergic receptors (AR). We investigated the effects of 20-min moderate (65-70% VO2 peak) exercise-induced catecholamine production on LPS-stimulated TNF production by monocytes in 47 healthy volunteers and determined AR subtypes involved. We also examined the effects of ß-agonist isoproterenol and endogenous ß- and α-agonists epinephrine and norepinephrine, and receptor-subtype-specific ß- and α-antagonists on TNF production in a series of in vitro investigations. LPS-stimulated TNF production by peripheral blood monocytes was determined intracellularly by flow cytometry, using an intracellular protein transport inhibitor. Percent TNF-producing monocytes and per-cell TNF production with and without LPS was suppressed by exercise with moderate to large effects, which was reversed by a ß2-AR antagonist in spite that plasma TNF levels did not change. This inhibitory response in TNF production by exercise was mirrored by ß-AR agonists in an agonist-specific and dose-dependent manner in vitro: similar isoproterenol (EC50=2.1-4.7×10-10M) and epinephrine (EC50=4.4-10×10-10M) potency and higher norepinephrine concentrations (EC50=2.6-4.3×10-8M) needed for the effects. Importantly, epinephrine levels observed during acute exercise in vivo significantly inhibited TNF production in vitro. The inhibitory effect of the AR agonists was abolished by ß2-, but not by ß1- or α-AR blockers. We conclude that the downregulation of monocytic TNF production during acute exercise is mediated by elevated epinephrine levels through ß2-ARs. Decreased inflammatory responses during acute exercise may protect against chronic conditions with low-grade inflammation.


Assuntos
Agonistas Adrenérgicos beta/farmacologia , Exercício Físico/fisiologia , Inflamação/metabolismo , Monócitos/metabolismo , Fator de Necrose Tumoral alfa/sangue , Agonistas alfa-Adrenérgicos/farmacologia , Adulto , Citocinas/metabolismo , Epinefrina/farmacologia , Feminino , Humanos , Isoproterenol/farmacologia , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Norepinefrina/farmacologia
14.
Schizophr Res ; 181: 63-69, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27650194

RESUMO

Chemokines are promising biomarkers of immune activation and inflammation, but evidence for chemokine abnormalities in schizophrenia and their relationship to clinical factors remains inconclusive. We aimed to understand chemokine-related diagnostic differences and clinical correlates using a comprehensive panel and studying a large, well-characterized sample of adults with and without schizophrenia. We studied 134 outpatients with schizophrenia or schizoaffective disorder and 112 healthy comparison (HC) individuals, 26 to 65years of age. Clinical measures were obtained, and plasma levels of 11 chemokines were assessed using multiplex immunoassay. Schizophrenia vs. HC differences were tested for each chemokine, adjusting for age, gender, body mass index, and current smoking status. We also examined whether age and gender relationships differed between diagnostic groups. Using logistic regression, we created a Chemokine Index (CI) and explored its clinical correlates. Levels of monocyte chemoattractant protein-1 (MCP-1/CCL2), macrophage inflammatory protein-1ß (MIP-1ß/CCL4), Eotaxin-1 (CCL11), thymus and activation-regulated chemokine (TARC/CCL17), and macrophage-derived chemokine (MDC/CCL22) were significantly higher in persons with schizophrenia than HCs. Group differences in TARC were reduced after adjusting for covariates. The CI, a linear combination of Eotaxin-1 and MDC levels, was positively associated with age, duration of schizophrenia, and severity of negative symptoms. Levels of chemokines with neuroimmune regulatory effects were higher in individuals with schizophrenia, particularly in older and chronic patients. Treatments aimed at normalizing chemokine levels might improve mental and physical health among schizophrenia patients as they age.


Assuntos
Quimiocinas/sangue , Transtornos Psicóticos/sangue , Transtornos Psicóticos/imunologia , Esquizofrenia/sangue , Esquizofrenia/imunologia , Adulto , Idoso , Envelhecimento/sangue , Envelhecimento/imunologia , Biomarcadores/sangue , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Imunoensaio , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Caracteres Sexuais
15.
Am J Geriatr Psychiatry ; 25(1): 50-61, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27840055

RESUMO

OBJECTIVE: Inflammation may play a role in the accelerated physical aging reported in schizophrenia, though biomarker findings and associations with demographic and clinical factors are inconsistent. METHODS: In a cross-sectional, case-control design, 95 outpatients with schizophrenia (mean age ± SD: 48.1 ± 10.2 years) and 95 demographically comparable healthy comparison subjects (HCs) (mean age ± SD: 48.1 ± 12.1 years) were studied. Sociodemographic and clinical data were collected, and plasma levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interferon-γ (IFN-γ) were assayed. The authors compared cytokine levels, examined demographic and clinical associations, and adjusted for relevant variables with linear models. RESULTS: Individuals with schizophrenia had higher levels of TNF-α and IL-6 but not IFN-γ than HCs. Age was not related to cytokine levels, and age relationships did not differ between diagnostic groups. Women had higher levels of IL-6. TNF-α and IL-6 levels were significantly correlated with depressive symptoms, and adjustment for depression reduced the group effect for both. Within the HCs, TNF-α levels were associated with physical comorbidity and body mass index. IL-6 levels were significantly correlated with body mass index and within schizophrenia patients, with worse mental and physical well-being. Accounting for physical morbidity and mental well-being reduced group differences in TNF-α and IL-6 levels, respectively. Worse positive symptoms were associated with higher IL-6 levels. CONCLUSION: Higher TNF-α and IL-6 levels in schizophrenia patients were associated with depression, physical comorbidity, and mental well-being. Further longitudinal studies are warranted to assess inflammation as a potential treatment target for a subgroup of schizophrenia.


Assuntos
Citocinas/sangue , Depressão/psicologia , Nível de Saúde , Inflamação/sangue , Satisfação Pessoal , Esquizofrenia/sangue , Adulto , Estudos de Casos e Controles , Comorbidade , Estudos Transversais , Depressão/epidemiologia , Feminino , Humanos , Inflamação/epidemiologia , Masculino , Pessoa de Meia-Idade , Esquizofrenia/epidemiologia
16.
J Acquir Immune Defic Syndr ; 74(2): 134-141, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27828873

RESUMO

BACKGROUND: HIV is associated with elevated markers of vascular remodeling that may contribute to arterial fibrosis and stiffening and changes in pulse pressure (PP). These changes may, in turn, deleteriously affect autoregulation of cerebral blood flow and neurocognitive function. METHODS: To evaluate these mechanisms, we studied markers of vascular remodeling, PP, and neurocognitive function among older (≥50 years of age) HIV-infected (HIV+, n = 72) and HIV-seronegative (HIV-, n = 36) adults. Participants completed standardized neurobehavioral and neuromedical assessments. Neurocognitive functioning was evaluated using a well-validated comprehensive battery. Three plasma biomarkers of vascular remodeling (ie, angiopoietin 2, Tie-2, and vascular endothelial growth factor, VEGF) were collected. RESULTS: HIV+ and HIV- participants had similar levels of plasma angiopoietin 2 (P = 0.48), Tie-2 (P = 0.27), VEGF (P = 0.18), and PP (P = 0.98). In a multivariable regression model, HIV interacted with Tie-2 (ß = 0.41, P < 0.01) and VEGF (ß = -0.43, P = 0.01) on neurocognitive function, such that lower Tie-2 and higher VEGF values were associated with worse neurocognitive function for HIV+ participants. Greater Tie-2 values were associated with increased PP (r = 0.31, P < 0.01). In turn, PP demonstrated a quadratic association with neurocognitive function (ß = -0.33, P = 0.01), such that lower and higher, relative to mean sample, PP values were associated with worse neurocognitive function. CONCLUSIONS: These findings indicate that vascular remodeling and altered cerebral blood flow autoregulation contribute to neurocognitive function. Furthermore, HIV moderates the association between vascular remodeling and neurocognitive function but not the association between PP and neurocognitive function.


Assuntos
Complexo AIDS Demência/etiologia , Complexo AIDS Demência/patologia , Antirretrovirais/uso terapêutico , Infecções por HIV/complicações , Resposta Viral Sustentada , Remodelação Vascular , Rigidez Vascular , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiopoietina-2/sangue , Biomarcadores/sangue , Estudos de Coortes , Feminino , Infecções por HIV/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Receptor TIE-2/sangue , Fator A de Crescimento do Endotélio Vascular/sangue
17.
Psychoneuroendocrinology ; 66: 195-204, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26829709

RESUMO

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is observed in various conditions, including depression and obesity, which are also often related. Glucocorticoid (GC) resistance and desensitization of peripheral GC receptors (GRs) are often the case in HPA dysregulation seen in depression, and GC plays a critical role in regulation of inflammation. Given the growing evidence that inflammation is a central feature of some depression cases and obesity, we aimed to investigate the immune-regulatory role of GC-GR in relation to depressive mood and obesity in 35 healthy men and women. Depressive mood and level of obesity were assessed, using Beck Depression Inventory (BDI-Ia) and body mass index (BMI), respectively. We measured plasma cortisol levels via enzyme-linked immunosorbent assay and lipopolysaccharide-stimulated intracellular tumor necrosis factor (TNF) production by monocytes, using flow cytometry. Cortisol sensitivity was determined by the difference in monocytic TNF production between the conditions of 1 and 0 µM cortisol incubation ("cortisol-mediated inflammation regulation, CoMIR"). GR vs. mineralocorticoid receptor (MR) antagonism for CoMIR was examined by using mifepristone and spironolactone. A series of multiple regression analyses were performed to investigate independent contribution of depressive mood vs. obesity after controlling for age, gender, systolic blood pressure (SBP), and plasma cortisol in predicting CoMIR. CoMIR was explained by somatic subcomponents of depressive mood (BDI-S: ß=-0.499, p=0.001), or BMI (ß=-0.466, p<0.01) in separate models. The effects of BMI disappeared when BDI-S was controlled for in the model, while BDI-S remained a significant independent predictor for CoMIR (ß=-0.369, p<0.05). However, BMI remained the only independent predictor when BDI-T or BDI-C were controlled for in the model. Mediation analyses also revealed that the relationship between BMI and CoMIR was mediated by BDI-S. The exploratory findings of the relative GR vs. MR roles in CoMIR, using GR and MR blockers, indicated that CoMIR in our cellular model was predominantly mediated by GRs at the higher cortisol dose (1 µM). There was initial indication that greater obesity and somatic depressive symptoms were associated with smaller efficacy of the blockers, which warrants further investigation. Our findings, although in a preclinical sample, signify the shared pathophysiology of immune dysregulation in depression and obesity and warrant further mechanistic investigation.


Assuntos
Depressão/imunologia , Inflamação/sangue , Monócitos/efeitos dos fármacos , Obesidade/imunologia , Adulto , Afeto/efeitos dos fármacos , Células Cultivadas , Depressão/sangue , Feminino , Glucocorticoides/farmacologia , Humanos , Hidrocortisona/sangue , Inflamação/imunologia , Inflamação/psicologia , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Obesidade/sangue , Obesidade/psicologia , Adulto Jovem
18.
Brain Behav Immun ; 50: 31-38, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26300225

RESUMO

Overwhelming data indicate that individuals with even mildly elevated blood pressure (BP) are at great risk for developing clinical hypertension and future cardiovascular disease (CVD). There remains a lack of consensus regarding treatment strategies for mildly elevated BP, termed prehypertension, and the knowledge of pathophysiology and mechanisms of its clinical outcomes remains limited. Our primary aim was to investigate ßAR-mediated inflammation control (BARIC) responses of blood monocytes to isoproterenol (Iso) in relation to BP and CVD risk factors, including obesity, depressive mood, fasting glucose, triglycerides, and cholesterol levels in the 64 prehypertensive compared to 84 individuals with normal BP. BARIC was determined by measuring the degree of inhibition in lipopolysaccharides-stimulated monocytic intracellular TNF production by ex vivo Iso treatment (10(-8)M). Depressive mood was assessed by Beck Depression Inventory (BDI). Fasting metabolic and lipid panels were assessed, and plasma levels of inflammatory cytokines TNF, IL-1ß, IL-6 were measured in a subset to confirm proinflammatory state of prehypertensive participants. Prehypertensive participants were older, heavier, included more men, and presented higher levels of fasting glucose, triglycerides, cholesterol, and plasma TNF compared to normotensive participants (p's<.05). BARIC was significantly attenuated in the prehypertensive compared to normotensive group (p<.05). BARIC was negatively associated with systolic BP, diastolic BP, age, BMI, fasting glucose, triglycerides, total and low density cholesterol levels, and somatic depressive symptoms in all participants (p's<.0001 to .05). However, among the prehypertensive individuals BARIC was positively associated with SBP even after controlling for the covariates (age, gender, race, BMI, glucose and lipid panel, somatic BDI scores) (p<.05). This differing nature of the BARIC-SBP relationship between the two BP groups may be attributed to moderating factors such as cardiorespiratory fitness or depressive symptoms that could not be clearly deciphered in this current study. Nonetheless, our findings indicate the associations between inflammation dysregulation mediated by sympathoadrenal activation and BP that is observable even among individuals with normal to mildly elevated BP. BARIC may be a useful and sensitive indicator of elevated risk for vascular inflammatory disease that can be detected even at lower BP levels, especially given its associations with traditional CVD risk factors and the critical role of monocytes in atherogenic processes.


Assuntos
Agonistas Adrenérgicos beta/farmacologia , Doenças Cardiovasculares/metabolismo , Inflamação/metabolismo , Isoproterenol/farmacologia , Monócitos/metabolismo , Receptores Adrenérgicos beta/metabolismo , Adolescente , Adulto , Idoso , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Colesterol/sangue , Depressão/complicações , Feminino , Humanos , Inflamação/complicações , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Fatores de Risco , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
19.
Brain Behav Immun ; 49: 49-53, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25747743

RESUMO

OBJECTIVES: Stimuli that activate the sympathetic nervous system, such as acute psychological stress, rapidly invoke a robust mobilization of lymphocytes into the circulation. Experimental animal studies suggest that bone marrow-derived progenitor cells (PCs) also mobilize in response to sympathetic stimulation. Here we tested the effects of acute psychological stress and brief pharmacological ß-adrenergic (ßAR) stimulation on peripheral PC numbers in humans. METHODS: In two studies, we investigated PC mobilization in response to an acute speech task (n=26) and ßAR-agonist (isoproterenol) infusion (n=20). A subset of 8 participants also underwent the infusion protocol with concomitant administration of the ßAR-antagonist propranolol. Flow cytometry was used to enumerate lymphocyte subsets, total progenitor cells, total haematopoietic stem cells (HSC), early HSC (multi-lineage potential), late HSC (lineage committed), and endothelial PCs (EPCs). RESULTS: Both psychological stress and ßAR-agonist infusion caused the expected mobilization of total monocytes and lymphocytes and CD8(+) T lymphocytes. Psychological stress also induced a modest, but significant, increase in total PCs, HSCs, and EPC numbers in peripheral blood. However, infusion of a ßAR-agonist did not result in a significant change in circulating PCs. CONCLUSION: PCs are rapidly mobilized by psychological stress via mechanisms independent of ßAR-stimulation, although the findings do not exclude ßAR-stimulation as a possible cofactor. Considering the clinical and physiological relevance, further research into the mechanisms involved in stress-induced PC mobilization seems warranted.


Assuntos
Células-Tronco Mesenquimais/metabolismo , Receptores Adrenérgicos beta/metabolismo , Estresse Psicológico/metabolismo , Agonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Adulto , Ansiedade/imunologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/imunologia , Complexo CD3/imunologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/imunologia , Humanos , Isoproterenol/farmacologia , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Monócitos/imunologia , Propranolol/farmacologia , Fala , Estresse Psicológico/imunologia
20.
PLoS One ; 10(2): e0116526, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25719800

RESUMO

BACKGROUND: HIV associated neurocognitive disorders (HAND) continue to affect cognition and everyday functioning despite anti-retroviral treatment (ART). Previous studies focused on mechanisms related to monocyte/macrophage mediated inflammation. However, in the ART era, there is increasing evidence for the involvement of CD8+ T-cells in CNS pathogenesis. METHODS: To investigate the relationship between T-cell responses and neurocognitive impairment (NCI), cerebrospinal fluid (CSF) and peripheral blood CD4+ and CD8+ T-cell intracellular cytokine (IFNγ, IL-2, TNFα) and lytic marker (CD107a) expression were assessed in HIV infected subjects who underwent comprehensive neurocognitive (NC) evaluation and either initiated or changed ART. RESULTS: Data were collected from 31 participants at 70 visits. The frequency of cytokine expressing T-cells in CSF was significantly higher than in peripheral blood for CD4+T-cells: TNFα, IL-2, IFNγ and CD8+T-cells: IL-2 and IFNγ. Analysis of T-cell activity and NCI as a function of CSF HIV RNA levels suggested a general association between NCI, high CSF CD8+ (but not CD4+T-cell) cytokine expression and CSF HIV RNA <103 copies/ml (p<0.0001). Specifically, CSF CD8+ T-cell IFNγ expression correlated with severity of NCI (r = 0.57, p = 0.004). Multivariable analyses indicated that CSF CD8+T-cell IFNγ and myeloid activation (CD163) contributed equally and independently to cognitive status and a composite variable produced the strongest correlation with NCI (r = 0.83, p = 0.0001). In contrast, CD8+ cytolytic activity (CD107a expression) was negatively correlated with NCI (p = 0.05) but was dependent on CD4 levels >400/µl and low CSF HIV RNA levels (<103 copies/ml). In our longitudinal analysis of 16 subjects, higher CSF CD8+IFNγ expression at baseline predicted NC decline at follow-up (p = 0.02). Severity of NCI at follow-up correlated with level of residual HIV RNA in CSF. CONCLUSIONS: Presence of IFNγ expressing CD8+ T-cells, absence of cytolytic CD8+ T-cells, high myeloid activation, and failure of ART to suppress HIV replication in CSF contribute to increased risk of HAND.


Assuntos
Linfócitos T CD8-Positivos/metabolismo , Transtornos Cognitivos/patologia , Interferon gama/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Antirretrovirais/uso terapêutico , Antígenos CD/líquido cefalorraquidiano , Antígenos de Diferenciação Mielomonocítica/líquido cefalorraquidiano , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/imunologia , Transtornos Cognitivos/etiologia , Estudos de Coortes , Demografia , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Interleucina-2/líquido cefalorraquidiano , Proteína 1 de Membrana Associada ao Lisossomo/metabolismo , Masculino , Pessoa de Meia-Idade , RNA Viral/líquido cefalorraquidiano , Receptores de Superfície Celular , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/líquido cefalorraquidiano , Replicação Viral , Adulto Jovem
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