15 research outputs found

    Pathophysiology of major depression by clinical stages

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    The comprehension of the pathophysiology of the major depressive disorder (MDD) is essential to the strengthening of precision psychiatry. In order to determine the relationship between the pathophysiology of the MDD and its clinical progression, analyzed by severity of the depressive symptoms and sleep quality, we conducted a study assessing different peripheral molecular biomarkers, including the levels of plasma C-reactive protein (CRP), serum mature brain-derived neurotrophic factor (mBDNF), serum cortisol (SC), and salivary cortisol awakening response (CAR), of patients with MDD (n = 58) and a control group of healthy volunteers (n = 62). Patients with the first episode of MDD (n = 30) had significantly higher levels of CAR and SC than controls (n = 32) and similar levels of mBDNF of controls. Patients with treatment-resistant depression (TRD, n = 28) presented significantly lower levels of SC and CAR, and higher levels of mBDNF and CRP than controls (n = 30). An increased severity of depressive symptoms and worse sleep quality were correlated with levels low of SC and CAR, and with high levels of mBDNF. These results point out a strong relationship between the stages clinical of MDD and changes in a range of relevant biological markers. This can assist in the development of precision psychiatry and future research on the biological tests for depression

    Potential biomarkers of major depression diagnosis and chronicity

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    Background Molecular biomarkers are promising tools to be routinely used in clinical psychiatry. Among psychiatric diseases, major depression disorder (MDD) has gotten attention due to its growing prevalence and morbidity. Methods We tested some peripheral molecular parameters such as serum mature Brain-Derived Neurotrophic Factor (mBDNF), plasma C-Reactive Protein (CRP), serum cortisol (SC), and the salivary Cortisol Awakening Response (CAR), as well as the Pittsburgh sleep quality inventory (PSQI), as part of a multibiomarker panel for potential use in MDD diagnosis and evaluation of disease's chronicity using regression models, and ROC curve. Results For diagnosis model, two groups were analyzed: Patients in the first episode of major depression (MD: n = 30) and a healthy control (CG: n = 32). None of those diagnosis models tested had greater power than Hamilton Depression Rating Scale-6. For MDD chronicity, a group of patients with treatment-resistant major depression (TRD: n = 28) was tested across the MD group. The best chronicity model (p < 0.05) that discriminated between MD and TRD included four parameters, namely PSQI, CAR, SC, and mBDNF (AUC ROC = 0.99), with 96% of sensitivity and 93% of specificity. Conclusion These results indicate that changes in specific biomarkers (CAR, SC, mBDNF and PSQI) have potential on the evaluation of MDD chronicity, but not for its diagnosis. Therefore, these findings can contribute for further studies aiming the development of a stronger model to be commercially available and used in psychiatry clinical practice

    Changes in cortisol but not in brain-derived neurotrophic factor modulate the association between sleep disturbances and major depression

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    Sleep disturbance is a symptom consistently found in major depression and is associated with a longer course of illness, reduced response to treatment, increased risk of relapse and recurrence. Chronic insomnia has been associated with changes in cortisol and serum brain-derived neurotrophic factor (BDNF) levels, which in turn are also changed in major depression. Here, we evaluated the relationship between sleep quality, salivary cortisol awakening response (CAR), and serum BDNF levels in patients with sleep disturbance and treatment-resistant major depression (n = 18), and in a control group of healthy subjects with good (n = 21) and poor (n = 18) sleep quality. We observed that the patients had the lowest CAR and sleep duration of all three groups and a higher latency to sleep than the healthy volunteers with a good sleep profile. Besides, low CAR was correlated with more severe depressive symptoms and worse sleep quality. There was no difference in serum BDNF levels between groups with distinct sleep quality. Taken together, our results showed a relationship between changes in CAR and in sleep quality in patients with treatment-resistant depression, which were correlated with the severity of disease, suggesting that cortisol could be a physiological link between sleep disturbance and major depression

    Changes in inflammatory biomarkers are related to the antidepressant effects of Ayahuasca

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    Background: Ayahuasca is a traditional Amazon brew and its potential antidepressant properties have recently been explored in scientific settings. We conducted a double-blind placebo-controlled trial of ayahuasca with treatment-resistant depression patients (n = 28) and healthy controls (n = 45). Aims: We are evaluating the blood inflammatory biomarkers: C-reactive protein and interleukin 6, as a potential consequence of ayahuasca intake and their correlation with serum cortisol and brain-derived neurotrophic factor levels. Blood samples were collected at pre-treatment and 48 hours after substance ingestion to assess the concentration of inflammatory biomarkers, together with administration of the Montgomery-√Ésberg Depression Rating Scale. Results: At pre-treatment, patients showed higher C-reactive protein levels than healthy controls and a significant negative correlation between C-reactive protein and serum cortisol levels was revealed (rho = ‚Äď0.40, n = 14). C-reactive protein in those patients was not correlated with Montgomery-√Ésberg Depression Rating Scale scores. We observed a significant reduction of C-reactive protein levels across time in both patients and controls treated with ayahuasca, but not with placebo. Patients treated with ayahuasca showed a significant correlation (rho = + 0.57) between larger reductions of C-reactive protein and lower depressive symptoms at 48 hours after substance ingestion (Montgomery-√Ésberg Depression Rating Scale). No significant result with respect to interleukin 6 and brain-derived neurotrophic factor was found. Furthermore, these biomarkers did not predict the antidepressant response or remission rates observed. Conclusions: These findings enhance the understanding of the biological mechanisms behind the observed antidepressant effects of ayahuasca and encourage further clinical trials in adults with depression

    Time-perception network and default mode network are associated with temporal prediction in a periodic motion task

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    The updating of prospective internal models is necessary to accurately predict future observations. Uncertainty-driven internal model updating has been studied using a variety of perceptual paradigms, and have revealed engagement of frontal and parietal areas. In a distinct literature, studies on temporal expectations have also characterized a time-perception network, which relies on temporal orienting of attention. However, the updating of prospective internal models is highly dependent on temporal attention, since temporal attention must be reoriented according to the current environmental demands. In this study we used fMRI to evaluate to what extend the continuous manipulation of temporal prediction would recruit update-related areas and the time-perception network areas. We developed an exogenous temporal task that combines rhythm cueing and time-to-contact principles to generate implicit temporal expectation. Two patterns of motion were created: periodic (simple harmonic oscillation) and non-periodic (harmonic oscillation with variable acceleration). We found that non-periodic motion engaged the exogenous temporal orienting network, which includes the ventral premotor and inferior parietal cortices, and the cerebellum, as well as the presupplementary motor area, which has previously been implicated in internal model updating, and the motion-sensitive area MT+. Interestingly, we found a right-hemisphere preponderance suggesting the engagement of explicit timing mechanisms. We also show that the periodic motion condition, when compared to the non-periodic motion, activated a particular subset of the default-mode network (DMN) midline areas, including the left dorsomedial prefrontal cortex, anterior cingulate cortex, and bilateral posterior cingulate cortex/precuneus. It suggests that the DMN plays a role in processing contextually expected information and supports recent evidence that the DMN may reflect the validation of prospective internal models and predictive control. Taken together, our findings suggest that continuous manipulation of temporal predictions engages representations of temporal prediction as well as task-independent updating of internal models

    Visualizando a elabora√ß√£o da linguagem em surdos bil√≠ngues por meio da resson√Ęncia magn√©tica funcional

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    As l√≠nguas de sinais s√£o l√≠nguas naturais que compartilham as propriedades das l√≠nguas orais. Este estudo buscou visualizar as √°reas corticais ativadas em surdos bil√≠ngues em L√≠ngua Brasileira de Sinais e em L√≠ngua Portuguesa. As tarefas envolveram a elabora√ß√£o da linguagem. Foram feitos treze exames de Imagem por Resson√Ęncia Magn√©tica Funcional. Foi utilizada, ainda, uma sequ√™ncia de imagem ecoplanar para a aquisi√ß√£o BOLD (Blood Oxygen Level Dependent) e, para corregistro, foram buscadas imagens de alta resolu√ß√£o de todo o enc√©falo. Os mapas estat√≠sticos foram obtidos com o Modelo Geral Linear, utilizando o programa Brain Voyager.TM A tarefa de elabora√ß√£o da linguagem em L√≠ngua Brasileira de Sinais proporcionou ativa√ß√Ķes mais significativas do que a tarefa de elabora√ß√£o em L√≠ngua Portuguesa, sugerindo que os surdos bil√≠ngues apresentam maior compet√™ncia lingu√≠stica em l√≠ngua de sinais.Sign languages are natural languages that have the same properties of oral languages. This study aimed to identify the cortical areas activated in bilingual deaf subjects who communicate through Brazilian Sign Language and Portuguese Language. Tasks involved the production of language. Thirteen functional magnetic resonances imaging (fMRI) exams were performed. An Echo Planar Imaging (EPI) sequence was used to obtain the BOLD (Blood Oxygen Level Dependent), associated with a whole brain high resolution imaging for co-register. The statistical maps were obtained using the General Linear Model with Brain VoyagerTM software. The task of producing Brazilian Sign Language provided more significant activations than did the task of producing Portuguese Language, suggesting that bilingual deaf subjects present a higher language proficiency in sign language

    Behavioral and EEG effects of GABAergic manipulation of the nigro-tectal pathway in the Wistar audiogenic rat (WAR) strain II: An EEG wavelet analysis and retrograde neuronal tracer approach

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    The role of the substantia nigra pars reticulata (SNPr) and superior colliculus (SC) network in rat strains susceptible to audiogenic seizures still remain underexplored in epileptology. In a previous study from our laboratory, the GABAergic drugs bicuculline (BIC) and muscimol (MUS) were microinjected into the deep layers of either the anterior SC (aSC) or the posterior SC (pSC) in animals of the Wistar audiogenic rat (WAR) strain submitted to acoustic stimulation, in which simultaneous electroencephalographic (EEG) recording of the aSC, pSC, SNPr and striatum was performed. Only MUS microinjected into the pSC blocked audiogenic seizures. In the present study, we expanded upon these previous results using the retrograde tracer Fluorogold (FG) microinjected into the aSC and pSC in conjunction with quantitative EEG analysis (wavelet transform), in the search for mechanisms associated with the susceptibility of this inbred strain to acoustic stimulation. Our hypothesis was that the WAR strain would have different connectivity between specific subareas of the superior colliculus and the SNPr when compared with resistant Wistar animals and that these connections would lead to altered behavior of this network during audiogenic seizures. Wavelet analysis showed that the only treatment with an anticonvulsant effect was MUS microinjected into the pSC region, and this treatment induced a sustained oscillation in the theta band only in the SNPr and in the pSC. These data suggest that in WAR animals, there are at least two subcortical loops and that the one involved in audiogenic seizure susceptibility appears to be the pSC-SNPr circuit. We also found that WARs presented an increase in the number of FG + projections from the posterior SNPr to both the aSC and pSC (primarily to the pSC), with both acting as proconvulsant nuclei when compared with Wistar rats. We concluded that these two different subcortical loops within the basal ganglia are probably a consequence of the WAR genetic background. (C) 2012 Elsevier Inc. All rights reserved.FAPESP [03/12420-2, 03/01134-9, 05/58939-4, 05/513366-9, 06/60768-6, 2003/00873-2, 2007/50261-4, 03/11381-3, 03/00873-2]FAPESPPRODOCCAPES fellowshipPRODOC-CAPES fellowshipCNPqCNPqCAPESCAPESCNPQ Research FellowshipCNPQ Research FellowshipFAPESP-Cinapce [2005/56447-7]FAPESP/CINAPCEPRONEXPRONEXCAPES-PROAP-PROEXCAPESPROAPPROEXFAEPAFAEP

    CONTRIBUI√á√ēES DA SUPERCONDUTIVIDADE NA MEDICINA

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