Background: Late Onset Alzheimer's Disease (LOAD) is one of the most common debilitating causes o... more Background: Late Onset Alzheimer's Disease (LOAD) is one of the most common debilitating causes of dementia worldwide with heritability estimates ranging from 50-70%. Genome-wide association studies (GWAS) have identified more than 20 genetic loci in addition to APOEe4 that are associated with increased risk for LOAD. While most of these genes have weak effects, using a polygenic risk profile score (RPS) approach-a method that allows exploration of the influence of the cumulative effect of risk alleles-we and others have shown the negative influence of LOAD risk genes on brain structure (Chauhan et al., 2015) and function (Xiao et al., 2015 HBM) even in healthy volunteers. Identifying mechanisms, particularly genetic mechanisms that confer resilience to the detrimental effect of LOAD related risk genes on brain structure and function could provide a viable avenue to identify novel therapeutic targets for LOAD. To that end, in the current study, we explored the role of polymorphisms in the gene encoding Reelin (RELN), a glycoprotein that has been shown to be critical for neuronal development and synaptic plasticity (Kramer et al. 2011), on the detrimental effect of LOAD RPS on hippocampal function. Studies have shown that normal RELN levels are necessary to prevent abnormal phosphorylation of tau (Ohkubo et al., 2003) and beta-amyloidinduced suppression of long term potentiation and NMDA receptors (Durakoglugil et al., 2009). Methods: BOLD functional MRI images (GE 3 T MRI scanner, TR/TE ¼ 2000/28ms, flip angle ¼ 90 deg, FOV ¼ 64x64, 24 axial slices, 170 volumes) were collected for 265 right-handed Caucasian healthy volunteers (116 male, 149 female) from the age of 18 to 86 years (SD ¼ 14.17) while they performed a simple declarative memory task (SDMT). Images were motion-corrected, normalized to MNI space, and spatially smoothed (8mm FWHM) using SPM5. Odd's ratios of 22 independent SNPs, with Po1 Â 10-5 in Hollingworth's meta-analysis1 comprising four Alzheimer's disease GWAS datasets (GERAD1, EADI1, TGEN1, ADNI), spanning the regions of ABCA7,
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
O termo psicose é usado para descrever um estado mental em que o indivíduo perde o contato com a ... more O termo psicose é usado para descrever um estado mental em que o indivíduo perde o contato com a realidade, e a etapa inicial de manifestação dos sintomas psicóticos define o primeiro episódio psicótico (PEP). Este artigo apresenta conceitos e dados gerais sobre PEP, apresenta fatores de risco e provê orientações sobre o diagnóstico (inclusive diagnósticos diferenciais), tratamento e acompanhamento de pacientes com PEP, com destaque para o papel das emergências psiquiátricas. As diferentes fases das psicoses também são descritas. Como conclusão, os autores salientam a importância da identificação e investigação dos casos, o início precoce do tratamento e o acompanhamento aproximado e individualizado dos pacientes.
O termo psicose é usado para descrever um estado mental em que o indivíduo perde o contato com a ... more O termo psicose é usado para descrever um estado mental em que o indivíduo perde o contato com a realidade, e a etapa inicial de manifestação dos sintomas psicóticos define o primeiro episódio psicótico (PEP). Este artigo apresenta conceitos e dados gerais sobre PEP, apresenta fatores de risco e provê orientações sobre o diagnóstico (inclusive diagnósticos diferenciais), tratamento e acompanhamento de pacientes com PEP, com destaque para o papel das emergências psiquiátricas. As diferentes fases das psicoses também são descritas. Como conclusão, os autores salientam a importância da identificação e investigação dos casos, o início precoce do tratamento e o acompanhamento aproximado e individualizado dos pacientes.
Neuromodulation techniques for obsessive-compulsive disorder (OCD) treatment have expanded with g... more Neuromodulation techniques for obsessive-compulsive disorder (OCD) treatment have expanded with greater understanding of the brain circuits involved. Transcranial direct current stimulation (tDCS) might be a potential new treatment for OCD, although the optimal montage is unclear. To perform a systematic review on meta-analyses of repetitive transcranianal magnetic stimulation (rTMS) and deep brain stimulation (DBS) trials for OCD, aiming to identify brain stimulation targets for future tDCS trials and to support the empirical evidence with computer head modeling analysis. Systematic reviews of rTMS and DBS trials on OCD in Pubmed/MEDLINE were searched. For the tDCS computational analysis, we employed head models with the goal of optimally targeting current delivery to structures of interest. Only three references matched our eligibility criteria. We simulated four different electrodes montages and analyzed current direction and intensity. Although DBS, rTMS and tDCS are not directl...
The interest in non-invasive brain stimulation techniques is increasing in recent years. Among th... more The interest in non-invasive brain stimulation techniques is increasing in recent years. Among these techniques, transcranial direct current stimulation (tDCS) has been the subject of great interest among researchers because of its easiness to use, low cost, benign profile of side effects and encouraging results of research in the field. This interest has generated several studies and randomized clinical trials, particularly in psychiatry. In this review, we provide a summary of the development of the technique and its mechanism of action as well as a review of the methodological aspects of randomized clinical trials in psychiatry, including studies in affective disorders, schizophrenia, obsessive compulsive disorder, child psychiatry and substance use disorder. Finally, we provide an overview of tDCS use in cognitive enhancement as well as a discussion regarding its clinical use and regulatory and ethical issues. Although many promising results regarding tDCS efficacy were describe...
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