Electroconvulsive therapy does not alter the synaptic protein neurogranin in the cerebrospinal fluid of patients with major depression

Neurogranin (Ng) is a dendritic protein associated with synaptic plasticity, proposed to be a novel biomarker to measure synaptic dysfunction and degeneration in Alzheimer’s disease. Since electroconvulsive therapy (ECT) has been suggested to facilitate neurogenesis and neural plasticity, we tested whether ECT could modify CSF Ng concentrations measured before and after a course of ECT in 12 patients with major depression. CSF Ng concentrations did not change, but baseline levels were positively correlated with the therapeutic response

Rudimentary G-Quadruplex-Based Telomere Capping In Saccharomyces Cerevisiae

Telomere capping conceals chromosome ends from exonucleases and checkpoints, but the full range of capping mechanisms is not well defined. Telomeres have the potential to form G-quadruplex (G4) DNA, although evidence for telomere G4 DNA function in vivo is limited. In budding yeast, capping requires the Cdc13 protein and is lost at nonpermissive temperatures in cdc13-1 mutants. Here, we use several independent G4 DNA-stabilizing treatments to suppress cdc13-1 capping defects. These include overexpression of three different G4 DNA binding proteins, loss of the G4 DNA unwinding helicase Sgs1, or treatment with small molecule G4 DNA ligands. In vitro, we show that protein-bound G4 DNA at a 3\u27 overhang inhibits 5\u27-\u3e 3\u27 resection of a paired strand by exonuclease I. These findings demonstrate that, at least in the absence of full natural capping, G4 DNA can play a positive role at telomeres in vivo

Source-Reconstruction of Event-Related Fields Reveals Hyperfunction and Hypofunction of Cortical Circuits in Antipsychotic-Naive, First-Episode Schizophrenia Patients during Mooney Face Processing

Schizophrenia is characterized by dysfunctions in neural circuits that can be investigated with electrophysiological methods, such as EEG and MEG. In the present human study, we examined event-related fields (ERFs), in a sample of medication-naive, first-episode schizophrenia (FE-ScZ) patients (n � 14) and healthy control participants (n � 17) during perception of Mooney faces to investigate the integrity of neuromagnetic responses and their experience-dependent modification. ERF responses were analyzed for M100, M170, and M250components at the sensor and source levels. In addition, we analyzed peak latency and adaptation effects due to stimulus repetition. FE-ScZ patients were characterized by significantly impaired sensory processing, as indicated by a reduced discrimination index (A�). At the sensor level, M100 and M170 responses in FE-ScZ were within the normal range, whereas the M250 response was impaired. However, source localization revealed widespread elevated activity for M100 and M170 in FE-ScZ and delayed peak latencies for the M100 and M250 responses. In addition, M170 source activity in FE-ScZ was not modulated by stimulus repetitions. The present findings suggest that neural circuits in FE-ScZ may be characterized by a disturbed balance between excitation and inhibition that could lead to a failure to gate information flow and abnormal spreading of activity, which is compatible with dysfunctional glutamatergic neurotransmission

Synthesis of novel MMT/acyl-protected nucleo alanine monomers for the preparation of DNA/alanyl-PNA chimeras

Alanyl-peptide nucleic acid (alanyl-PNA)/DNA chimeras are oligomers envisaged to be beneficial in efficient DNA diagnostics based on an improved molecular beacon concept. A synthesis of alanyl-PNA/DNA chimera can be based on the solid phase assembly of the oligomer with mixed oligonucleotide/peptide backbone under DNA synthesis conditions, in which the nucleotides are introduced as phosphoramidites, whereas the nucleo amino acids make use of the acid labile monomethoxytrityl (MMT) group for temporary protection of the α-amino groups and acyl protecting groups for the exocyclic amino functions of the nucleobases. In this work, we realized for the first time the synthesis of all four MMT/acyl-protected nucleo alanines, achieved by deprotection/reprotection of the newly synthesized Boc/acyl intermediates, useful monomers for the obtainment of (alanyl-PNA)/DNA chimeras by conditions fully compatible with the standard phosphoramidite DNA synthesis strategy

Identification of a biological signature for schizophrenia in serum

Biomarkers are now used in many areas of medicine but are still lacking for psychiatric conditions such as schizophrenia (SCZ). We have used a multiplex molecular profiling approach to measure serum concentrations of 181 proteins and small molecules in 250 first and recent onset SCZ, 35 major depressive disorder (MDD), 32 euthymic bipolar disorder (BPD), 45 Asperger syndrome and 280 control subjects. Preliminary analysis resulted in identification of a signature comprised of 34 analytes in a cohort of closely matched SCZ (n = 71) and control (n = 59) subjects. Partial least squares discriminant analysis using this signature gave a separation of 60-75% of SCZ subjects from controls across five independent cohorts. The same analysis also gave a separation of similar to 50% of MDD patients and 10-20% of BPD and Asperger syndrome subjects from controls. These results demonstrate for the first time that a biological signature for SCZ can be identified in blood serum. This study lays the groundwork for development of a diagnostic test that can be used as an aid for distinguishing SCZ subjects from healthy controls and from those affected by related psychiatric illnesses with overlapping symptoms. Molecular Psychiatry (2012) 17, 494-502; doi:10.1038/mp.2011.42; published online 12 April 201

Evidence for Increased Genetic Risk Load for Major Depression in Patients Assigned to Electroconvulsive Therapy

Electroconvulsive therapy (ECT) is the treatment of choice for severe and treatment-resistant depression; disorder severity and unfavorable treatment outcomes are shown to be influenced by an increased genetic burden for major depression (MD). Here, we tested whether ECT assignment and response/nonresponse are associated with an increased genetic burden for major depression (MD) using polygenic risk score (PRS), which summarize the contribution of diseaserelated common risk variants. Fifty-one psychiatric inpatients suffering from a major depressive episode underwent ECT. MD-PRS were calculated for these inpatients and a separate population-based sample (n = 3,547 healthy; n = 426 self-reported depression) based on summary statistics from the Psychiatric Genomics Consortium MDD-working group (Cases: n = 59,851; Controls: n = 113,154). MD-PRS explained a significant proportion of disease status between ECT patients and healthy controls (p = .022, R2 = 1.173%); patients showed higher MD-PRS. MD-PRS in population-based depression self-reporters were intermediate between ECT patients and controls (n.s.). Significant associations between MD-PRS and ECT response (50% reduction in Hamilton depression rating scale scores) were not observed. Our findings indicate that ECT cohorts show an increased genetic burden for MD and are consistent with the hypothesis that treatment-resistant MD patients represent a subgroup with an increased genetic risk for MD. Larger samples are needed to better substantiate these findings

Reduced vascular endothelial growth factor levels in the cerebrospinal fluid in patients with treatment resistant major depression and the effects of electroconvulsive therapy—A pilot study

BACKGROUND: Several lines of evidence are pointing towards an involvement of the vascular endothelial growth factor (VEGF) in the pathophysiology of depression. There are studies analyzing blood levels of VEGF in patients with depression compared to controls, but a data on cerebrospinal fluid (CSF) levels of VEGF in patients with depression are lacking. METHOD: CSF VEGF levels were measured in patients (n = 12) with a severe, treatment-resistant depressive episode before and after the antidepressant treatment by a course of electroconvulsive therapy (ECT) and compared to age- and sex-matched controls (n = 20). RESULTS: The patients with depression showed lower mean VEGF levels in the CSF prior to ECT than the controls (p = 0.041). Regarding the patients, CSF VEGF concentration at baseline and after the complete ECT treatment did not differ from each other (p = 0.78). LIMITATIONS: Major limitations of this study are the small sample size and that data from corresponding serum levels cannot be provided. Another limitation is that the controls were not completely healthy, as they were recruited from a memory clinic with subjective complaints. The timing of the second sample might have been suboptimal, when taking into account that there might be an on-going phase of re-equilibrating after ECT. CONCLUSIONS: CSF VEGF concentrations were lower in a clinical sample of patients with treatment-resistant depression compared with matched controls. Additionally, no change in CSF VEGF levels during a course of ECT could be detected