Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 122
Filtrar
Mais filtros

Bases de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
2.
BMC Neurol ; 24(1): 347, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39285343

RESUMO

BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory neurodegenerative disease with diverse symptomatology, significantly impacting patients' quality of life (QoL). While pharmacological therapies focus primarily on reducing inflammation and relapse rates, non-pharmacological interventions, including digital health applications, have shown promise in improving QoL among persons with MS (PwMS). Pilot studies had shown the feasibility and acceptability of levidex, a digital health application based on cognitive behavioral therapy (CBT) principles, a broad set of behavior change techniques, and relevant lifestyle-change advice. This randomized controlled trial aimed to examine the effects of levidex on MS-related QoL over 6 months. METHODS: Participants who were diagnosed with MS for at least one year were recruited via the internet in Germany, using a secure survey software platform, and were randomly assigned to the intervention group (IG), in which they received standard care + levidex, or an active control group (CG), in which they received standard care and were offered web-adapted material on the topic of lifestyle change from the German Multiple Sclerosis Society (DMSG). The primary outcome was MS-related QoL after 6 months, measured by the Hamburg Quality of Life Questionnaire in MS (HAQUAMS); secondary outcomes included QoL subscales, sick days, and health behavior, among others. Analyses of Covariance (ANCOVA) were used to examine intervention effects at 6 months. Participants were recruited between November 2020 and February 2022. RESULTS: A total of 421 adult participants (mean age: 47.5, 78.1% women) were included and randomized (IG, n = 195, CG, n = 226). After 6 months, the IG exhibited significantly higher MS-related QoL, compared to the CG (total score HAQUAMS, adjusted group mean difference = -0.14, 95% CI: [-0.22, -0.06], p = 0.001; Cohen's d = 0.23), with significant effects also observed on the cognitive and mood subscales. At 6 months, IG participants also reported significantly fewer sick days (median = 2 days in IG vs. 6 days in CG; W = 3939, p = 0.012) and significantly higher levels of daily activities, as measured by the Frenchay Activity Index, adjusted group mean difference = 1.37, 95% CI = [0.33, 2.40], p = 0.010; Cohen's d = 0.16. Safety analyses showed no adverse events and good satisfaction. CONCLUSIONS: Compared to the control group, levidex facilitated clinically relevant improvements in MS-related QoL, reduced sick days, and enhanced activity in PwMS over 6 months. These findings suggest that levidex can serve as an effective non-pharmacological adjunctive treatment element to standard care and could help improve QoL among PwMS. TRIAL REGISTRATION: Registered on 22.09.2020 at the German Clinical Trials Register DRKS00023023.


Assuntos
Terapia Cognitivo-Comportamental , Esclerose Múltipla , Qualidade de Vida , Humanos , Feminino , Qualidade de Vida/psicologia , Masculino , Esclerose Múltipla/psicologia , Esclerose Múltipla/terapia , Adulto , Pessoa de Meia-Idade , Terapia Cognitivo-Comportamental/métodos , Estilo de Vida , Resultado do Tratamento
3.
J Neurosci Res ; 101(1): 143-161, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36263462

RESUMO

Multiple sclerosis (MS) is an inflammatory and demyelinating disease which leads to impairment in several functional systems including cognition. Alteration of brain networks is linked to disability and its progression. However, results are mostly cross-sectional and yet contradictory as putative adaptive and maladaptive mechanisms were found. Here, we aimed to explore longitudinal reorganization of brain networks over 2-years by combining diffusion tensor imaging (DTI), resting-state functional MRI (fMRI), magnetoencephalography (MEG), and a comprehensive neuropsychological-battery. In 37 relapsing-remitting MS (RRMS) and 39 healthy-controls, cognition remained stable over-time. We reconstructed network models based on the three modalities and analyzed connectivity in relation to the hierarchical topology and functional subnetworks. Network models were compared across modalities and in their association with cognition using linear-mixed-effect-regression models. Loss of hub connectivity and global reduction was observed on a structural level over-years (p < .010), which was similar for functional MEG-networks but not for fMRI-networks. Structural hub connectivity increased in controls (p = .044), suggesting a physiological mechanism of healthy aging. Despite a general loss in structural connectivity in RRMS, hub connectivity was preserved (p = .002) over-time in default-mode-network (DMN). MEG-networks were similar to DTI and weakly correlated with fMRI in MS (p < .050). Lower structural (ß between .23-.33) and both lower (ß between .40-.59) and higher functional connectivity (ß = -.54) in DMN was associated with poorer performance in attention and memory in RRMS (p < .001). MEG-networks involved no association with cognition. Here, cognitive stability despite ongoing neurodegeneration might indicate a resilience mechanism of DMN hubs mimicking a physiological reorganization observed in healthy aging.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Esclerose Múltipla Recidivante-Remitente/complicações , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Imagem de Tensor de Difusão , Mapeamento Encefálico , Estudos Transversais , Testes Neuropsicológicos , Encéfalo/diagnóstico por imagem , Cognição , Imageamento por Ressonância Magnética , Vias Neurais/diagnóstico por imagem
4.
J Neurol Neurosurg Psychiatry ; 94(9): 718-725, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36807056

RESUMO

The influence of pregnancy on the course of multiple sclerosis (MS) has long been controversial. While historical evidence suggests a substantial decline in relapse rates during pregnancy followed by a rebound in the postpartum period, more recent work yielded equivocal results. We performed a systematic review and meta-analysis on data from cohort studies to determine whether women with MS experience increased relapse rates after delivery. A systematic literature search was conducted in the databases MEDLINE and Epistemonikos on the topic 'motherhood choice in MS' in March 2022. We included cohort studies assessing the association between pregnancy and MS relapse activity defined by the annualised relapse rate after 3, 6, 9 and 12 months post partum. Furthermore, information about disease-modifying therapies (DMT) and breast feeding was considered, if available. 5369 publications were identified. Of these, 93 full-text articles on MS relapse activity during the postpartum period were screened. 11 studies including 2739 pregnancies were eligible. Women with MS showed a significantly increased relapse rate in the first 6 months post partum, compared with preconception with the incidence rate ratio (IRR) almost doubled in the first 3 months post partum (1.87, 95% CI 1.40 to 2.50). However, at 10-12 months post partum, the IRR decreased significantly (0.81, 95% CI 0.67 to 0.98). Subanalysis on influencing parameters suggested that preconceptional DMTs (IRR for highly-effective DMTs 2.76, 95% CI 1.34 to 5.69) and exclusive breast feeding (risk ratio 0.39, 95% CI 0.18 to 0.86) significantly influenced postpartum relapse risk. Increased postpartum annualised relapse rate and possible modifiers should be considered in counselling women with MS who are considering pregnancy.


Assuntos
Esclerose Múltipla , Complicações na Gravidez , Gravidez , Feminino , Humanos , Esclerose Múltipla/complicações , Complicações na Gravidez/epidemiologia , Período Pós-Parto , Estudos de Coortes , Doença Crônica , Recidiva
5.
Mol Psychiatry ; 27(3): 1286-1299, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34907394

RESUMO

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD.


Assuntos
Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Humanos
6.
Mult Scler ; 29(13): 1561-1568, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37880962

RESUMO

BACKGROUND: Exercise as a subset of physical activity is a cornerstone in the management of multiple sclerosis (MS) based on its pleiotropic effects, but continued progression of the field requires better future designs and methodologies. OBJECTIVES: This paper outlines the work of the 'Study design and methodology' group of the MoXFo (moving exercise research forward) initiative, and addresses critical aspects and future directions when defining the research question of interest, and subsequently, designing the study and exercise intervention in MS patients. METHODS: The work is based on the formation of an international expert panel formed within the MoXFo initiative. We provide a structured and concise synthesis of exercise-specific MS research challenges and considerations when designing randomized controlled trials (RCTs). RESULTS: Challenges and considerations are presented using the Patient population, Intervention, Comparator, Outcomes, Timing, Setting (PICOTS) framework, thereby forming a new and specific MS exercise PICOTS framework. CONCLUSION: We propose that researchers should carefully consider and align all elements of this MS exercise PICOTS framework when developing future research questions and study designs, ultimately improving the quality of new exercise studies in people with MS.


Assuntos
Esclerose Múltipla , Humanos , Esclerose Múltipla/terapia , Exercício Físico , Terapia por Exercício , Projetos de Pesquisa
7.
Addict Biol ; 28(7): e13287, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37369124

RESUMO

Social exclusion contributes to alcohol consumption, whereas the development of alcohol dependence (AD) can in turn lead to the social exclusion of people with AD. Previous research observed altered neural responses to experimentally induced social exclusion (i.e., Cyberball game) in patients with AD. In addition, inflammation has been associated with both social behaviours and AD. Our study aimed to investigate the dynamic behavioural response and the inflammatory effects of social exclusion in male patients with a history of AD. To this end, we analysed dynamic changes in ball tossing during a partial exclusion Cyberball game and the cytokine interleukin (IL)-1b in saliva in 31 male patients who had a history of AD and 29 gender-matched healthy controls without AD. Participants were included in the first 2 min of the Cyberball game and then excluded by one of the two co-players in the proceeding 5 min. Saliva was collected three times: one before and two after the Cyberball game. Across groups, participants passed the ball more often to the excluder during the partial exclusion period. Analysis using piece-wise linear mixed models showed that patients rapidly increased ball tosses to the excluder upon exclusion, which lasted to the late response phase, whereas the early behavioural response to exclusion took longer for controls. There was no significant change of salivary IL-1b level to exclusion in either patients or controls. The results indicate a distinct dynamic behavioural response to social exclusion in male patients with a history of AD.


Assuntos
Alcoolismo , Humanos , Masculino , Isolamento Social , Comportamento Social
8.
Brain Behav Immun ; 103: 223-231, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35491003

RESUMO

INTRODUCTION: Depression and obesity often occur comorbidly, and once both are present, they further increase the risk of developing other medical comorbidities, likely due to the underlying chronic low-grade inflammation. We investigated to what extent depression and obesity are associated with levels of high-sensitivity C-reactive protein (hsCRP) in a nationally representative sample of the German adult population. METHODS: We analyzed data from the German Health Interview and Examination Survey for Adults (DEGS1, N = 7115), and its mental health module (DEGS1-MH; N = 4483). Two different depression measures were used: current depressive symptoms assessed by the self-administered German version of the Patient Health Questionnaire-9 and major depressive disorder (MDD) in the last 12 months assessed by a modified German version of the Composite International Diagnostic Interview. Obesity was defined by body mass index calculated from measured data. Associations with log(x + 1)-transformed hsCRP levels were analyzed using multivariable linear regression models. RESULTS: Obese participants with depressive symptoms had significantly higher hsCRP compared to non-obese participants with depressive symptoms adjusted for sociodemographic and behavioral variables and medication use. In non-obese individuals, depressive symptoms were inversely associated with hsCRP, whereas MDD was not associated with hsCRP after adjustment for covariates. Additional analyses suggested symptom-specific associations of hsCRP as higher levels were linked to fatigue (ß = 0.10, p <.001) while lower levels were linked to cognitive problems (ß = -0.09, p <.001). Low SES, current smoking, lower levels of physical exercise, and the use of anti-inflammatory/anti-rheumatic medication and antidepressants were additional determinants of hsCRP in the fully adjusted models. CONCLUSIONS: Our data suggest that obesity status is more strongly associated with increased inflammation than depressive symptoms or MDD. The relationship between depression and hsCRP in our population-based sample is substantially influenced by obesity status as well as other medical factors, lifestyle, and socioeconomic status. Furthermore, our findings suggest that the association between hsCRP and depression is symptom-specific rather than generalized.


Assuntos
Proteína C-Reativa , Transtorno Depressivo Maior , Adulto , Anti-Inflamatórios , Proteína C-Reativa/metabolismo , Estudos Transversais , Depressão/diagnóstico , Depressão/epidemiologia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/epidemiologia , Alemanha/epidemiologia , Humanos , Inflamação/epidemiologia , Inflamação/psicologia , Obesidade/epidemiologia
9.
Brain Behav Immun ; 100: 174-182, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34863857

RESUMO

Multiple neurobiological pathways have been implicated in the pathobiology of major depressive disorder (MDD). The identification of reliable biological substrates across the entire MDD spectrum, however, is hampered by a vast heterogeneity in the clinical presentation, presumably as a consequence of heterogeneous pathobiology. One way to overcome this limitation could be to explore disease subtypes based on biological similarity such as "inflammatory depression". As such a subtype may be particularly enriched in depressed patients with an underlying inflammatory condition, multiple sclerosis (MS) could provide an informative disease context for this approach. Few studies have explored immune markers of MS-associated depression and replications are missing. To address this, we analyzed data from two independent case-control studies on immune signatures of MS-associated depression, conducted at two different academic MS centers (overall sample size of n = 132). Using a stepwise data-driven approach, we identified CD4+CCR7lowTCM cell frequencies as a robust correlate of depression in MS. This signature was associated with core symptoms of depression and depression severity (but not MS severity per se) and linked to neuroinflammation as determined by magnetic resonance imaging (MRI). Furthermore, exploratory analyses of T cell polarization revealed this was largely driven by cells with a TH1-like phenotype. Our findings suggest (neuro)immune pathways linked to affective symptoms of autoimmune disorders such as MS, with potential relevance for the understanding of "inflammatory" subtypes of depression.


Assuntos
Transtorno Depressivo Maior , Esclerose Múltipla , Biomarcadores , Estudos de Casos e Controles , Depressão/metabolismo , Transtorno Depressivo Maior/complicações , Humanos , Esclerose Múltipla/complicações , Esclerose Múltipla/metabolismo
10.
BMC Med Res Methodol ; 22(1): 228, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35971069

RESUMO

BACKGROUND: Platform trials can evaluate the efficacy of several experimental treatments compared to a control. The number of experimental treatments is not fixed, as arms may be added or removed as the trial progresses. Platform trials are more efficient than independent parallel group trials because of using shared control groups. However, for a treatment entering the trial at a later time point, the control group is divided into concurrent controls, consisting of patients randomised to control when that treatment arm is in the platform, and non-concurrent controls, patients randomised before. Using non-concurrent controls in addition to concurrent controls can improve the trial's efficiency by increasing power and reducing the required sample size, but can introduce bias due to time trends. METHODS: We focus on a platform trial with two treatment arms and a common control arm. Assuming that the second treatment arm is added at a later time, we assess the robustness of recently proposed model-based approaches to adjust for time trends when utilizing non-concurrent controls. In particular, we consider approaches where time trends are modeled either as linear in time or as a step function, with steps at time points where treatments enter or leave the platform trial. For trials with continuous or binary outcomes, we investigate the type 1 error rate and power of testing the efficacy of the newly added arm, as well as the bias and root mean squared error of treatment effect estimates under a range of scenarios. In addition to scenarios where time trends are equal across arms, we investigate settings with different time trends or time trends that are not additive in the scale of the model. RESULTS: A step function model, fitted on data from all treatment arms, gives increased power while controlling the type 1 error, as long as the time trends are equal for the different arms and additive on the model scale. This holds even if the shape of the time trend deviates from a step function when patients are allocated to arms by block randomisation. However, if time trends differ between arms or are not additive to treatment effects in the scale of the model, the type 1 error rate may be inflated. CONCLUSIONS: The efficiency gained by using step function models to incorporate non-concurrent controls can outweigh potential risks of biases, especially in settings with small sample sizes. Such biases may arise if the model assumptions of equality and additivity of time trends are not satisfied. However, the specifics of the trial, scientific plausibility of different time trends, and robustness of results should be carefully considered.


Assuntos
Tamanho da Amostra , Viés , Humanos
11.
Hum Brain Mapp ; 42(11): 3379-3395, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33826184

RESUMO

Although multiple sclerosis (MS) is frequently accompanied by visuo-cognitive impairment, especially functional brain mechanisms underlying this impairment are still not well understood. Consequently, we used a functional MRI (fMRI) backward masking task to study visual information processing stratifying unconscious and conscious in MS. Specifically, 30 persons with MS (pwMS) and 34 healthy controls (HC) were shown target stimuli followed by a mask presented 8-150 ms later and had to compare the target to a reference stimulus. Retinal integrity (via optical coherence tomography), optic tract integrity (visual evoked potential; VEP) and whole brain structural connectivity (probabilistic tractography) were assessed as complementary structural brain integrity markers. On a psychophysical level, pwMS reached conscious access later than HC (50 vs. 16 ms, p < .001). The delay increased with disease duration (p < .001, ß = .37) and disability (p < .001, ß = .24), but did not correlate with conscious information processing speed (Symbol digit modality test, ß = .07, p = .817). No association was found for VEP and retinal integrity markers. Moreover, pwMS were characterized by decreased brain activation during unconscious processing compared with HC. No group differences were found during conscious processing. Finally, a complementary structural brain integrity analysis showed that a reduced fractional anisotropy in corpus callosum and an impaired connection between right insula and primary visual areas was related to delayed conscious access in pwMS. Our study revealed slowed conscious access to visual stimulus material in MS and a complex pattern of functional and structural alterations coupled to unconscious processing of/delayed conscious access to visual stimulus material in MS.


Assuntos
Encéfalo/patologia , Disfunção Cognitiva/fisiopatologia , Estado de Consciência/fisiologia , Potenciais Evocados Visuais/fisiologia , Esclerose Múltipla/patologia , Esclerose Múltipla/fisiopatologia , Rede Nervosa/patologia , Reconhecimento Visual de Modelos/fisiologia , Retina/patologia , Adulto , Encéfalo/diagnóstico por imagem , Córtex Cerebral , Disfunção Cognitiva/etiologia , Imagem de Tensor de Difusão , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Mascaramento Perceptivo/fisiologia , Retina/diagnóstico por imagem , Fatores de Tempo
12.
Acta Neuropathol ; 142(4): 643-667, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34170374

RESUMO

The complement system is implicated in synapse loss in the MS hippocampus, but the functional consequences of synapse loss remain poorly understood. Here, in post-mortem MS hippocampi with demyelination we find that deposits of the complement component C1q are enriched in the CA2 subfield, are linked to loss of inhibitory synapses and are significantly higher in MS patients with cognitive impairments compared to those with preserved cognitive functions. Using the cuprizone mouse model of demyelination, we corroborated that C1q deposits are highest within the demyelinated dorsal hippocampal CA2 pyramidal layer and co-localized with inhibitory synapses engulfed by microglia/macrophages. In agreement with the loss of inhibitory perisomatic synapses, we found that Schaffer collateral feedforward inhibition but not excitation was impaired in CA2 pyramidal neurons and accompanied by intrinsic changes and a reduced spike output. Finally, consistent with excitability deficits, we show that cuprizone-treated mice exhibit impaired encoding of social memories. Together, our findings identify CA2 as a critical circuit in demyelinated intrahippocampal lesions and memory dysfunctions in MS.


Assuntos
Região CA2 Hipocampal/metabolismo , Região CA2 Hipocampal/patologia , Complemento C1q/metabolismo , Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologia , Sinapses/fisiologia , Idoso , Animais , Estudos de Casos e Controles , Cuprizona , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Esclerose Múltipla/etiologia
13.
Mult Scler ; 27(7): 989-1001, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33720795

RESUMO

BACKGROUND: People with multiple sclerosis (MS) experience myriad symptoms that negatively affect their quality of life. Despite significant progress in rehabilitation strategies for people living with relapsing-remitting MS (RRMS), the development of similar strategies for people with progressive MS has received little attention. OBJECTIVE: To highlight key symptoms of importance to people with progressive MS and stimulate the design and implementation of high-quality studies focused on symptom management and rehabilitation. METHODS: A group of international research experts, representatives from industry, and people affected by progressive MS was convened by the International Progressive MS Alliance to devise research priorities for addressing symptoms in progressive MS. RESULTS: Based on information from the MS community, we outline a rationale for highlighting four symptoms of particular interest: fatigue, mobility and upper extremity impairment, pain, and cognitive impairment. Factors such as depression, resilience, comorbidities, and psychosocial support are described, as they affect treatment efficacy. CONCLUSIONS: This coordinated call to action-to the research community to prioritize investigation of effective symptom management strategies, and to funders to support them-is an important step in addressing gaps in rehabilitation research for people affected by progressive MS.


Assuntos
Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Qualidade de Vida , Pesquisa de Reabilitação
14.
J Immunol ; 203(7): 1743-1752, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31444265

RESUMO

Disease activity of autoimmune disorders such as multiple sclerosis and its mouse model experimental autoimmune encephalomyelitis (EAE) is temporarily suppressed by pregnancy. However, whether disease amelioration is due to nonspecific immunomodulation or mediated by Ag-specific regulation of disease-causing conventional T cells (Tcon) and immunosuppressive regulatory T cells (Tregs) remains elusive. In the current study, we systematically analyzed changes of the TCRß repertoire driven by EAE and pregnancy using TCR sequencing. We demonstrate that EAE, but not pregnancy, robustly increased TCR repertoire clonality in both peripheral Tcon and Treg. Notably, pregnancy was required for the expansion of Treg harboring the dominant EAE-associated TRBV13-2 chain and increased the frequency of EAE-associated clonotypes within the Treg compartment. Our findings indicate that pregnancy supports the expansion of Treg clonotypes that are equipped to recognize EAE-associated Ags. These Treg are thereby particularly suited to control corresponding encephalitogenic Tcon responses and likely contribute to pregnancy-associated protection in autoimmunity.


Assuntos
Encefalomielite Autoimune Experimental/imunologia , Esclerose Múltipla/imunologia , Complicações na Gravidez/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Linfócitos T Reguladores/imunologia , Animais , Autoantígenos/genética , Autoantígenos/imunologia , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/patologia , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Esclerose Múltipla/genética , Esclerose Múltipla/patologia , Gravidez , Complicações na Gravidez/patologia , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Linfócitos T Reguladores/patologia
15.
Cell Biochem Funct ; 39(3): 423-431, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33401342

RESUMO

In this pilot study, we explored the immune phenotype of patients with severe obesity and comorbid depressive symptoms compared to non-depressed patients with obesity and normal-weight controls. Immune cell subsets were analysed by flow cytometry and depressive symptoms assessed using the Patient Health Questionnaire (PHQ-9). Cell frequencies were correlated with depressive symptom scores and waist-to-hip ratio (WHR). Patients with obesity and comorbid depression showed significantly lower numbers of circulating cytotoxic natural killer cells, dendritic cells and CD8+ effector memory T cells, compared to normal-weight controls. Regulatory T cells and CD4+ central memory T cells were increased compared to non-depressed patients with obesity and compared to normal-weight controls, respectively. Frequencies of cytotoxic natural killer cells and CD4+ central memory T cells significantly correlated with PHQ-9 scores, but not with WHR. Reduced numbers of dendritic cells were observed in both patient groups with obesity and correlated with PHQ-9 scores and WHR. These findings provide evidence for an altered immune composition in comorbid obesity and depression, supporting a pathobiological overlap between the two disorders.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Depressão/imunologia , Memória Imunológica , Obesidade Mórbida/imunologia , Adulto , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Células Dendríticas/patologia , Depressão/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/patologia , Projetos Piloto , Inquéritos e Questionários
16.
Psychol Med ; 50(12): 2075-2084, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31462343

RESUMO

BACKGROUND: Across psychopathologies, trauma-exposed individuals suffer from difficulties in inhibiting emotions and regulating attention. In trauma-exposed individuals without psychopathology, only subtle alterations of neural activity involved in regulating emotions have been reported. It remains unclear how these neural systems react to demanding environments, when acute (non-traumatic but ordinary) stress serves to perturbate the system. Moreover, associations with subthreshold clinical symptoms are poorly understood. METHODS: The present fMRI study investigated response inhibition of emotional faces before and after psychosocial stress situations. Specifically, it compared 25 women (mean age 31.5 ± 9.7 years) who had suffered severe early life trauma but who did not have a history of or current psychiatric disorder, with 25 age- and education-matched trauma-naïve women. RESULTS: Under stress, response inhibition related to fearful faces was reduced in both groups. Compared to controls, trauma-exposed women showed decreased left inferior frontal gyrus (IFG) activation under stress when inhibiting responses to fearful faces, while activation of the right anterior insula was slightly increased. Also, groups differed in brain-behaviour correlations. Whereas stress-induced false alarm rates on fearful stimuli negatively correlated with stress-induced IFG signal in controls, in trauma-exposed participants, they positively correlated with stress-induced insula activation. CONCLUSION: Neural facilitation of emotion inhibition during stress appears to be altered in trauma-exposed women, even without a history of or current psychopathology. Decreased activation of the IFG in concert with heightened bottom-up salience of fear related cues may increase vulnerability to stress-related diseases.


Assuntos
Expressão Facial , Medo/psicologia , Acontecimentos que Mudam a Vida , Córtex Pré-Frontal/fisiopatologia , Estresse Psicológico/complicações , Adulto , Mapeamento Encefálico , Feminino , Humanos , Inibição Psicológica , Imageamento por Ressonância Magnética , Adulto Jovem
17.
Proc Natl Acad Sci U S A ; 114(2): E181-E190, 2017 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-28049829

RESUMO

Pregnancy is one of the strongest inducers of immunological tolerance. Disease activity of many autoimmune diseases including multiple sclerosis (MS) is temporarily suppressed by pregnancy, but little is known about the underlying molecular mechanisms. Here, we investigated the endocrine regulation of conventional and regulatory T cells (Tregs) during reproduction. In vitro, we found the pregnancy hormone progesterone to robustly increase Treg frequencies via promiscuous binding to the glucocorticoid receptor (GR) in T cells. In vivo, T-cell-specific GR deletion in pregnant animals undergoing experimental autoimmune encephalomyelitis (EAE), the animal model of MS, resulted in a reduced Treg increase and a selective loss of pregnancy-induced protection, whereas reproductive success was unaffected. Our data imply that steroid hormones can shift the immunological balance in favor of Tregs via differential engagement of the GR in T cells. This newly defined mechanism confers protection from autoimmunity during pregnancy and represents a potential target for future therapy.


Assuntos
Gravidez/imunologia , Receptores de Glucocorticoides/imunologia , Linfócitos T/imunologia , Animais , Autoimunidade , Encefalomielite Autoimune Experimental/imunologia , Feminino , Tolerância Imunológica , Camundongos Endogâmicos C57BL , Progesterona/imunologia
18.
Proc Natl Acad Sci U S A ; 113(47): 13444-13449, 2016 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-27821732

RESUMO

Prospective clinical studies support a link between psychological stress and multiple sclerosis (MS) disease severity, and peripheral stress systems are frequently dysregulated in MS patients. However, the exact link between neurobiological stress systems and MS symptoms is unknown. To evaluate the link between neural stress responses and disease parameters, we used an arterial-spin-labeling functional MRI stress paradigm in 36 MS patients and 21 healthy controls. Specifically, we measured brain activity during a mental arithmetic paradigm with performance-adaptive task frequency and performance feedback and related this activity to disease parameters. Across all participants, stress increased heart rate, perceived stress, and neural activity in the visual, cerebellar and insular cortex areas compared with a resting condition. None of these responses was related to cognitive load (task frequency). Consistently, although performance and cognitive load were lower in patients than in controls, stress responses did not differ between groups. Insula activity elevated during stress compared with rest was negatively linked to impairment of pyramidal and cerebral functions in patients. Cerebellar activation was related negatively to gray matter (GM) atrophy (i.e., positively to GM volume) in patients. Interestingly, this link was also observed in overlapping areas in controls. Cognitive load did not contribute to these associations. The results show that our task induced psychological stress independent of cognitive load. Moreover, stress-induced brain activity reflects clinical disability in MS. Finally, the link between stress-induced activity and GM volume in patients and controls in overlapping areas suggests that this link cannot be caused by the disease alone.


Assuntos
Encéfalo/patologia , Avaliação da Deficiência , Esclerose Múltipla/patologia , Esclerose Múltipla/psicologia , Estresse Psicológico/patologia , Atrofia , Mapeamento Encefálico , Cognição , Demografia , Feminino , Substância Cinzenta/patologia , Frequência Cardíaca/fisiologia , Humanos , Hidrocortisona/metabolismo , Imageamento por Ressonância Magnética , Masculino , Matemática , Pessoa de Meia-Idade , Tamanho do Órgão , Saliva/metabolismo , Estresse Psicológico/complicações , Análise e Desempenho de Tarefas , Substância Branca/patologia
19.
J Neurol Neurosurg Psychiatry ; 89(9): 970-976, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29549193

RESUMO

OBJECTIVE: Fatigue is a major disabling symptom in many chronic diseases including multiple sclerosis (MS), but treatment options are limited.Here, we tested the effectiveness of a self-guided , interactive, online fatigue management programme (ELEVIDA) based on principles of cognitive behavioural therapy (CBT) and related psychotherapeutic approaches (eg, mindfulness) for reducing fatigue in MS. METHODS: Patients with MS and self-reported fatigue were recruited via the website of the German MS Society and assigned via an automated randomisation generator (1:1, no blocking or stratification) to a 12-week online intervention (ELEVIDA, n=139, 82% female, mean age 40.8, median patient determined disease steps (PDDS) 3.0) or a waitlist control group (n=136, 79% female, mean age 41.9, median PDDS 3.0). The primary outcome was the Chalder Fatigue Scale. Outcomes were assessed at baseline, at week 12 (postintervention) and at follow-up (week 24). RESULTS: Compared with the control group, significantly greater reductions in Chalder Fatigue Scale scores were seen in the ELEVIDA group at week 12 (primary endpoint, intention-to-treat analysis: between-group mean difference 2.74 points; 95% CI 1.16 to 4.32; p=0.0007; effect size d=0.53), with effects sustained at week 24 (intention-to-treat analysis: between-group mean difference 2.19 points; 95% CI 0.57 to 3.82; p=0.0080). CONCLUSIONS: Our trial provides evidence for the effectiveness of a self-guided , internet-based intervention to reduce fatigue in MS. Interventions such as ELEVIDA may be a suitable low barrier, cost-effective treatment option for MS fatigue. TRIAL REGISTRATION NUMBER: ISRCTN registry (number ISRCTN25692173).


Assuntos
Terapia Cognitivo-Comportamental/métodos , Fadiga/terapia , Internet , Esclerose Múltipla/complicações , Autocuidado/métodos , Adulto , Fadiga/diagnóstico , Fadiga/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Autorrelato
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA