BDNF Val66Met polymorphism and protein levels in Amniotic Fluid

Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin which plays survival- and growth-promoting activity in neuronal cells and it is involved in cellular plasticity mechanisms as it controls activity dependent synaptic transmission. A functional polymorphism (Val66Met) in the pro-region of BDNF, which affects the intracellular trafficking of proBDNF has been associated with memory and cognitive deficits as well as to an increased susceptibility for several psychiatric disorders especially those with a neurodevelopmental origin. To date, no study has evaluated the influence of the Val66Met polymorphism on BDNF levels in a peripheral system that may reflect fetal neurodevelopment. Therefore we investigated in amniotic fluids (AF) obtained from 139 healthy women during 15-17 week of pregnancy, BDNF protein levels in correlation with the Val66Met polymorphism

CONTREX: Design of embedded mixed-criticality CONTRol systems under consideration of EXtra-functional properties

The increasing processing power of today’s HW/SW platforms leads to the integration of more and more functions in a single device. Additional design challenges arise when these functions share computing resources and belong to different criticality levels. The paper presents the CONTREX European project and its preliminary results. CONTREX complements current activities in the area of predictable computing platforms and segregation mechanisms with techniques to consider the extra-functional properties, i.e., timing constraints, power, and temperature. CONTREX enables energy efficient and cost aware design through analysis and optimization of these properties with regard to application demands at different criticality levels

CONTREX: Design of embedded mixed-criticality CONTRol systems under consideration of EXtra-functional properties

The increasing processing power of today’s HW/SW platforms leads to the integration of more and more functions in a single device. Additional design challenges arise when these functions share computing resources and belong to different criticality levels. CONTREX complements current activities in the area of predictable computing platforms and segregation mechanisms with techniques to consider the extra-functional properties, i.e., timing constraints, power, and temperature. CONTREX enables energy efficient and cost aware design through analysis and optimization of these properties with regard to application demands at different criticality levels. This article presents an overview of the CONTREX European project, its main innovative technology (extension of a model based design approach, functional and extra-functional analysis with executable models and run-time management) and the final results of three industrial use-cases from different domain (avionics, automotive and telecommunication).The work leading to these results has received funding from the European Community’s Seventh Framework Programme FP7/2007-2011 under grant agreement no. 611146

Alterations observed in the interferon α and β signaling pathway in MDD patients are marginally influenced by cis-acting alleles

Abstract Major depressive disorder (MDD) is a common psychiatric disorder with a multifactorial aetiology determined by the interaction between genetic and environmental risk factors. Pieces of evidence indicate that inflammation and immune activation may contribute to the onset of MDD playing a role in the pathogenetic mechanism. To date, it is not known to which extent the association between MDD and inflammation is shaped by the genetic background or by the presence of environmental factors. To clarify this issue, we analyzed genotype and blood RNA profiles of 463 MDD cases and 459 controls (NIMH-Study 88/Site621) estimating the Genetic and Environmental Regulated eXpression component of gene expression (GReX and EReX respectively). Both components were tested for association with MDD. Many genes belonging to the α/β interferon signaling pathway showed an association between MDD and EReX, only two between MDD and GReX. Also other MDD differentially expressed genes were more influenced by the EReX than by GReX. These results suggest that impact of the genetic background on MDD blood gene expression alterations is much lower than the contribution of environmental factors and almost absent for the genes of the interferon pathway

Reduced peripheral brain-derived neurotrophic factor mRNA levels are normalized by antidepressant treatment

Consistent data coming from biochemical studies have evidenced a brain-derived neurotrophic factor (BDNF) serum reduction in depressed patients compared to controls and a restoration following antidepressant treatment. However, to date, no study has evaluated whether BDNF synthesis in leukocytes could contribute to such modulation. Therefore, in this study, we analysed BDNF mRNA levels in leukocytes from 21 depressed patients prior to and during escitalopram treatment and from 23 control subjects showing that BDNF mRNA levels were decreased in drug-free depressed patients and that 12 wk escitalopram treatment was able to reverse this deficit. Interestingly, changes in BDNF mRNA levels paralleled BDNF serum increase during antidepressant treatment, and were correlated with symptoms improvement. Our results indicate that BDNF serum modulation observed in depressed patients is associated with BDNF synthesis alteration in leukocytes and suggest that these peripheral cells might play an active role in the mechanisms of action of antidepressants

BDNF Genotype and Baseline Serum Levels in Relation to Electroconvulsive Therapy Effectiveness in Treatment-Resistant Depressed Patients

Electroconvulsive therapy (ECT) represents one of the most effective therapies for treatment-resistant depression (TRD). The brain-derived neurotrophic factor (BDNF) is a neurotrophin implicated in major depressive disorder and in the effects of different therapeutic approaches, including ECT. Both BDNF peripheral levels and Val66Met polymorphism have been suggested as biomarkers of treatment effectiveness. The objective of this study was to test the potential of serum BDNF levels and Val66Met polymorphism in predicting ECT outcome in TRD patients