Early B-cell Factor gene association with multiple sclerosis in the Spanish population

BACKGROUND: The etiology of multiple sclerosis (MS) is at present not fully elucidated, although it is considered to result from the interaction of environmental and genetic susceptibility factors. In this work we aimed at testing the Early B-cell Factor (EBF1) gene as a functional and positional candidate risk factor for this neurological disease. Axonal damage is a hallmark for multiple sclerosis clinical disability and EBF plays an evolutionarily conserved role in the expression of proteins essential for axonal pathfinding. Failure of B-cell differentiation was found in EBF-deficient mice and involvement of B-lymphocytes in MS has been suggested from their presence in cerebrospinal fluid and lesions of patients. METHODS: The role of the EBF1 gene in multiple sclerosis susceptibility was analyzed by performing a case-control study with 356 multiple sclerosis patients and 540 ethnically matched controls comparing the EBF1 polymorphism rs1368297 and the microsatellite D5S2038. RESULTS: Significant association of an EBF1-intronic polymorphism (rs1368297, A vs. T: p = 0.02; OR = 1.26 and AA vs. [TA+TT]: p = 0.02; OR = 1.39) was discovered. This association was even stronger after stratification for the well-established risk factor of multiple sclerosis in the Major Histocompatibility Complex, DRB1*1501 (AA vs. [TA+TT]: p = 0.005; OR = 1.78). A trend for association in the case-control study of another EBF1 marker, the allele 5 of the very informative microsatellite D5S2038, was corroborated by Transmission Disequilibrium Test of 53 trios (p = 0.03). CONCLUSION: Our data support EBF1 gene association with MS pathogenesis in the Spanish white population. Two genetic markers within the EBF1 gene have been found associated with this neurological disease, indicative either of their causative role or that of some other polymorphism in linkage disequilibrium with them

Developmental expression of COE across the Metazoa supports a conserved role in neuronal cell-type specification and mesodermal development

The transcription factor COE (collier/olfactory-1/early B cell factor) is an unusual basic helix–loop–helix transcription factor as it lacks a basic domain and is maintained as a single copy gene in the genomes of all currently analysed non-vertebrate Metazoan genomes. Given the unique features of the COE gene, its proposed ancestral role in the specification of chemosensory neurons and the wealth of functional data from vertebrates and Drosophila, the evolutionary history of the COE gene can be readily investigated. We have examined the ways in which COE expression has diversified among the Metazoa by analysing its expression from representatives of four disparate invertebrate phyla: Ctenophora (Mnemiopsis leidyi); Mollusca (Haliotis asinina); Annelida (Capitella teleta and Chaetopterus) and Echinodermata (Strongylocentrotus purpuratus). In addition, we have studied COE function with knockdown experiments in S. purpuratus, which indicate that COE is likely to be involved in repressing serotonergic cell fate in the apical ganglion of dipleurula larvae. These analyses suggest that COE has played an important role in the evolution of ectodermally derived tissues (likely primarily nervous tissues) and mesodermally derived tissues. Our results provide a broad evolutionary foundation from which further studies aimed at the functional characterisation and evolution of COE can be investigated

Altered Metabolism and Lipodystrophy in the Early B-Cell Factor 1-Deficient Mouse

We previously reported that mice deficient for the transcription factor early B-cell factor (Ebf1) exhibit markedly increased numbers of osteoblasts, bone formation rate, and serum osteocalcin, but the bone marrow of Ebf1−/− mice is also striking in its increased marrow adiposity. The purpose of this work was to analyze the metabolic phenotype that accompanies the altered bone morphology of Ebf1−/− mice. Whereas marrow adiposity was increased, deposition of white adipose tissue in other regions of the body was severely reduced (sc 40–50%, abdominally 80–85%). Brown adipose exhibited decreased lipid deposition. Subcutaneous and perigonadal white adipose tissue showed a decrease in mRNA transcripts for peroxisomal proliferator-activated receptor-γ2 and CCAAT/enhancer-binding protein-β in Ebf1−/− tissue compared with wild type. Circulating levels of leptin were decreased in Ebf1−/− animals compared with their littermate controls (down 65-95%), whereas adiponectin remained comparable after 2 wk of age. Serum analysis also found the Ebf1−/− animals were hypoglycemic and hypotriglyceridemic. After ip injection of insulin, the serum glucose levels in Ebf1−/− mice took longer to recover, and after a glucose challenge the Ebf1−/− animals reached serum glucose levels almost twice that of their wild-type counterparts. Measurement of circulating pancreatic hormones revealed normal or reduced insulin levels in the Ebf1−/− mice, whereas glucagon was significantly increased (up 1.7- to 8.5-fold). Metabolically the Ebf1−/− mice had increased O2 consumption, CO2 production, food and water intake, and activity. Markers for gluconeogenesis, however, were decreased in the Ebf1−/− mice compared with controls. In conclusion, the Ebf1-deficient animals exhibit defects in adipose tissue deposition with increased marrow adiposity and impaired glucose mobilization

12-month outcome and predictors of recurrence in psychiatric treatment of depression – a retrospective study.

Many individuals treated for depression suffer relapse or recurrence after treatment. Known risk factors include number of previous depressive episodes and residual symptoms after treatment. Both relapse/recurrence rates and predictors of relapse/recurrence, however, may differ between various settings. To perform a naturalistic evaluation of the sustained effectiveness of treatment for adult clinical depression in a psychiatric out-patient setting and to examine psychosocial and clinical predictors of relapse/recurrence. 51 individuals, who were successfully treated/discharged from psychiatric care 12 months prior, were assessed regarding current depressive status and regarding relapse and recurrence. Logistic regression was used to assess the predictive impact of the variables measured. At the 12-month follow-up, 26 % of the participants were in complete remission, 45 % were in partial remission, and 29 % were clinically depressed. In 1 year, 61 % suffered a new depressive episode. Having a greater number of previous episodes and having no partner significantly increased the risk of relapse or recurrence. A high prevalence of depression and partially remitted depression is reported at 12-month follow up, and a large proportion of the sample would likely benefit from active treatment. Relapse/recurrence rates are higher in this study than in many other studies, and it may be hypothesized that they are generally higher in psychiatric settings than in primary care. If so, this would indicate the need for a different treatment strategy in the psychiatric care of depression, with emphasis on long-term management of depression

Adesão e não-adesão ao tratamento farmacológico para depressão

O presente estudo objetivou compreender aspectos relacionados à adesão e a não-adesão ao tratamento farmacológico para depressão, envolvendo usuários e ex-usuários de um serviço público de saúde mental. Foram entrevistados, individualmente, 24 pacientes (12 aderentes e 12 não aderentes ao tratamento medicamentoso para depressão). Por meio da análise de conteúdo das entrevistas, identificou-se que o fenômeno da adesão/não-adesão estaria inter-relacionado a aspectos intrapessoais, interpessoais e ao contexto do tratamento do paciente. Os resultados fomentaram reflexões acerca do papel de equipes de saúde mental no incremento da adesão ao tratamento, bem como da necessidade de uma maior consideração do indivíduo, da família e do atendimento prestado pela instituição