Loss of CX3CR1 increases accumulation of inflammatory monocytes and promotes gliomagenesis

The most abundant populations of non-neoplastic cells in the glioblastoma (GBM) microenvironment are resident microglia, macrophages and infiltrating monocytes from the blood circulation. The mechanisms by which monocytes infiltrate into GBM, their fate following infiltration, and their role in GBM growth are not known. Here we tested the hypothesis that loss of the fractalkine receptor CX3CR1 in microglia and monocytes would affect gliomagenesis. Deletion of Cx3cr1 from the microenvironment resulted in increased tumor incidence and shorter survival times in glioma-bearing mice. Loss of Cx3cr1 did not affect accumulation of microglia/macrophages in peri-tumoral areas, but instead indirectly promoted the trafficking of CD11b+CD45hiCX3CR1lowLy-6ChiLy-6G-F4/80-/low circulating inflammatory monocytes into the CNS, resulting in their increased accumulation in the perivascular area. Cx3cr1-deficient microglia/macrophages and monocytes demonstrated upregulation of IL1{beta} expression that was inversely proportional to Cx3cr1 gene dosage. The Proneural subgroup of the TCGA GBM patient dataset with high IL1{beta} expression showed shorter survival compared to patients with low IL1{beta}. IL1{beta} promoted tumor growth and increased the cancer stem cell phenotype in murine and human Proneural glioma stem cells (GSCs). IL1{beta} activated the p38 MAPK signaling pathway and expression of monocyte chemoattractant protein (MCP-1/CCL2) by tumor cells. Loss of Cx3cr1 in microglia in a monocyte-free environment had no impact on tumor growth and did not alter microglial migration. These data suggest that enhancing signaling to CX3CR1 or inhibiting IL1{beta} signaling in intra-tumoral macrophages can be considered as potential strategies to decrease the tumor-promoting effects of monocytes in Proneural GBM

Can We Really Prevent Suicide?

Every year, suicide is among the top 20 leading causes of death globally for all ages. Unfortunately, suicide is difficult to prevent, in large part because the prevalence of risk factors is high among the general population. In this review, clinical and psychological risk factors are examined and methods for suicide prevention are discussed. Prevention strategies found to be effective in suicide prevention include means restriction, responsible media coverage, and general public education, as well identification methods such as screening, gatekeeper training, and primary care physician education. Although the treatment for preventing suicide is difficult, follow-up that includes pharmacotherapy, psychotherapy, or both may be useful. However, prevention methods cannot be restricted to the individual. Community, social, and policy interventions will also be essentia

EEG Markers in Emotionally Unstable Personality Disorder-A Possible Outcome Measure for Neurofeedback: A Narrative Review.

Objectives. There is growing evidence for the use of biofeedback (BF) in affective disorders, dissocial personality disorder, and in children with histories of abuse. Electroencephalogram (EEG) markers could be used as neurofeedback in emotionally unstable personality disorder (EUPD) management especially for those at high risk of suicide when emotionally aroused. This narrative review investigates the evidence for EEG markers in EUPD. Methods. PRISMA guidelines were used to conduct a narrative review. A structured search method was developed and implemented in collaboration with an information specialist. Studies were identified via 3 electronic database searches of MEDLINE, Embase, and PsycINFO. A predesigned inclusion/exclusion criterion was applied to selected papers. A thematic analysis approach with 5 criteria was used. Results. From an initial long list of 5250 papers, 229 studies were identified and screened, of which 44 met at least 3 of the predesigned inclusion criteria. No research to date investigates EEG-based neurofeedback in EUPD. A number of different EEG biomarkers are identified but there is poor consistency between studies. Conclusions. The findings heterogeneity may be due to the disorder complexity and the variable EEG related parameters studied. An alternative explanation may be that there are a number of different neuromarkers, which could be clustered together with clinical symptomatology, to give new subdomains. Quantitative EEGs in particular may be helpful to identify more specific abnormalities. EEG standardization of neurofeedback protocols based on specific EEG abnormalities detected may facilitate targeted use of neurofeedback as an intervention in EUPD

Revisiting the Dexamethasone Suppression Test in unipolar major depression: an exploratory study

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Prediction and prevention of suicide in patients with unipolar depression and anxiety

Epidemiological data suggest that between 59 and 87% of suicide victims suffered from major depression while up to 15% of these patients will eventually commit suicide. Male gender, previous suicide attempt(s), comorbid mental disorders, adverse life-situations, acute psycho-social stressors etc. also constitute robust risk factors. Anxiety and minor depression present with a low to moderate increase in suicide risk but anxiety-depression comorbidity increases this risk dramatically Contrary to the traditional psychoanalytic approach which considers suicide as a retrospective murder or an aggression turned in-wards, more recent studies suggest that the motivations to commit suicide may vary and are often too obscure. Neurobiological data suggest that low brain serotonin activity might play a key role along with the tryptophan hydroxylase gene. Social factors include social support networks, religion etc. It is proven that most suicide victims had asked for professional help just before committing suicide, however they were either not diagnosed (particularly males) or the treatment they received was inappropriate or inadequate. The conclusion is that promoting suicide prevention requires the improving of training and skills of both psychiatrists and many non-psychiatrists and especially GPs in recognizing and treating depression and anxiety. A shift of focus of attention is required in primary care to detect potentially suicidal patients presenting with psychological problems. The proper use of antidepressants, after a careful diagnostic evaluation, is important and recent studies suggest that successful acute and long-term antidepressant pharmacotherapy reduces suicide morbidity and mortality

The emerging modern face of mood disorders: a didactic editorial with a detailed presentation of data and definitions

The present work represents a detailed description of our current understanding and knowledge of the epidemiology, etiopathogenesis and clinical manifestations of mood disorders, their comorbidity and overlap, and the effect of variables such as gender and age. This review article is largely based on the 'Mood disorders' chapter of the Wikibooks Textbook of Psychiatry http://en.wikibooks.org/wiki/Textbook_of_Psychiatry/Mood_Disorders