Modulating Affect, Cognition, and Behavior – Prospects of Deep Brain Stimulation for Treatment-Resistant Psychiatric Disorders

Most patients suffering from psychiatric disorders respond to combinations of psycho- and psychopharmacotherapy; however there are patients who profit little if anything even after many years of treatment. Since about a decade different modalities of targeted neuromodulation – among them most prominently – deep brain stimulation (DBS) – are being actively researched as putative approaches to very treatment-resistant forms of those disorders. Recently, promising pilot data have been reported both for major depression (MD) and obsessive–compulsive disorder (OCD). Given the fact that patients included in DBS studies had been treated unsuccessfully for many years with conventional treatment methods, renders these findings remarkable. Remarkable is the fact, that in case of the long-term studies underway for MD, patients show a stable response. This gives hope to a substantial percentage of therapy–resistant psychiatric patients requiring new therapy approaches. There are no fundamental ethic objections to its use in psychiatric disorders, but until substantial clinical data is available, mandatory standards are needed. DBS is a unique and very promising method for the treatment of therapy–resistant psychiatric patients. The method allows manipulating pathological neuronal networks in a very precise way

Suicide reporting in the Swiss print media: Frequency, form and content of articles

All the Swiss newspapers were screened for the target words ‘suicide' and ‘attempted suicide' and all relevant articles were analysed for form and content over a period of 8 months. In 151 out of 208 articles suiclde/attempted suicide was the major topic. Large differences between the newspapers regarding the frequency and format of the articles (e.g. placement on front page) were found. In a few newspapers with a large circulation suicide is clearly treated as a major topic of news sensation. The majority of articles reported cases of completed suicide, mainly shooting and hanging by young persons. Attempted suicide was only reported for persons with celebrity status. This survey shows that there is reason for concern in view of the danger of imitation effect

PSYCHIATRY

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HIV-Specific Cellular Immune Response Is Inversely Correlated with Disease Progression as Defined by Decline of CD4+ T Cells in Relation to HIV RNA Load

The average time between infection with human immunodeficiency virus (HIV) and development of acquired immune deficiency syndrome is ∼8 years. However, progression rates vary widely, depending on several determinants, including HIV-specific immunity, host genetic factors, and virulence of the infecting strain. In untreated HIV-infected patients with different progression rates, we examined HIV-specific T cell responses in combination with host genetic markers, such as chemokine/chemokine-receptor (CCR) polymorphisms and human leukocyte antigen (HLA) genotypes. HIV-specific CD4+ T cell responses and, to a lesser extent, HIVspecific CD8+ T cell responses were inversely correlated with progression rate. Slower progression was not related to polymorphisms in CCR genes, HLA genotype, or GB virus C coinfection. These data suggest that HIV-specific T cell responses are involved in protecting the host from disease progressio

Introduced Mammalian Predators Induce Behavioural Changes in Parental Care in an Endemic New Zealand Bird

The introduction of predatory mammals to oceanic islands has led to the extinction of many endemic birds. Although introduced predators should favour changes that reduce predation risk in surviving bird species, the ability of island birds to respond to such novel changes remains unstudied. We tested whether novel predation risk imposed by introduced mammalian predators has altered the parental behaviour of the endemic New Zealand bellbird (Anthornis melanura). We examined parental behaviour of bellbirds at three woodland sites in New Zealand that differed in predation risk: 1) a mainland site with exotic predators present (high predation risk), 2) a mainland site with exotic predators experimentally removed (low risk recently) and, 3) an off-shore island where exotic predators were never introduced (low risk always). We also compared parental behaviour of bellbirds with two closely related Tasmanian honeyeaters (Phylidonyris spp.) that evolved with native nest predators (high risk always). Increased nest predation risk has been postulated to favour reduced parental activity, and we tested whether island bellbirds responded to variation in predation risk. We found that females spent more time on the nest per incubating bout with increased risk of predation, a strategy that minimised activity at the nest during incubation. Parental activity during the nestling period, measured as number of feeding visits/hr, also decreased with increasing nest predation risk across sites, and was lowest among the honeyeaters in Tasmania that evolved with native predators. These results demonstrate that some island birds are able to respond to increased risk of predation by novel predators in ways that appear adaptive. We suggest that conservation efforts may be more effective if they take advantage of the ability of island birds to respond to novel predators, especially when the elimination of exotic predators is not possible

Transcriptional Changes Common to Human Cocaine, Cannabis and Phencyclidine Abuse

A major goal of drug abuse research is to identify and understand drug-induced changes in brain function that are common to many or all drugs of abuse. As these may underlie drug dependence and addiction, the purpose of the present study was to examine if different drugs of abuse effect changes in gene expression that converge in common molecular pathways. Microarray analysis was employed to assay brain gene expression in postmortem anterior prefrontal cortex (aPFC) from 42 human cocaine, cannabis and/or phencyclidine abuse cases and 30 control cases, which were characterized by toxicology and drug abuse history. Common transcriptional changes were demonstrated for a majority of drug abuse cases (N = 34), representing a number of consistently changed functional classes: Calmodulin-related transcripts (CALM1, CALM2, CAMK2B) were decreased, while transcripts related to cholesterol biosynthesis and trafficking (FDFT1, APOL2, SCARB1), and Golgi/endoplasmic reticulum (ER) functions (SEMA3B, GCC1) were all increased. Quantitative PCR validated decreases in calmodulin 2 (CALM2) mRNA and increases in apolipoprotein L, 2 (APOL2) and semaphorin 3B (SEMA3B) mRNA for individual cases. A comparison between control cases with and without cardiovascular disease and elevated body mass index indicated that these changes were not due to general cellular and metabolic stress, but appeared specific to the use of drugs. Therefore, humans who abused cocaine, cannabis and/or phencyclidine share a decrease in transcription of calmodulin-related genes and increased transcription related to lipid/cholesterol and Golgi/ER function. These changes represent common molecular features of drug abuse, which may underlie changes in synaptic function and plasticity that could have important ramifications for decision-making capabilities in drug abusers

Phosphorylation of p130Cas initiates Rac activation and membrane ruffling

<p>Abstract</p> <p>Background</p> <p>Non-receptor tyrosine kinases (NTKs) regulate physiological processes such as cell migration, differentiation, proliferation, and survival by interacting with and phosphorylating a large number of substrates simultaneously. This makes it difficult to attribute a particular biological effect to the phosphorylation of a particular substrate. We developed the Functional Interaction Trap (FIT) method to phosphorylate specifically a single substrate of choice in living cells, thereby allowing the biological effect(s) of that phosphorylation to be assessed. In this study we have used FIT to investigate the effects of specific phosphorylation of p130Cas, a protein implicated in cell migration. We have also used this approach to address a controversy regarding whether it is Src family kinases or focal adhesion kinase (FAK) that phosphorylates p130Cas in the trimolecular Src-FAK-p130Cas complex.</p> <p>Results</p> <p>We show here that SYF cells (mouse fibroblasts lacking the NTKs Src, Yes and Fyn) exhibit a low level of basal tyrosine phosphorylation at focal adhesions. FIT-mediated tyrosine phosphorylation of NTK substrates p130Cas, paxillin and FAK and cortactin was observed at focal adhesions, while FIT-mediated phosphorylation of cortactin was also seen at the cell periphery. Phosphorylation of p130Cas in SYF cells led to activation of Rac1 and increased membrane ruffling and lamellipodium formation, events associated with cell migration. We also found that the kinase activity of Src and not FAK is essential for phosphorylation of p130Cas when the three proteins exist as a complex in focal adhesions.</p> <p>Conclusion</p> <p>These results demonstrate that tyrosine phosphorylation of p130Cas is sufficient for its localization to focal adhesions and for activation of downstream signaling events associated with cell migration. FIT provides a valuable tool to evaluate the contribution of individual components of the response to signals with multiple outputs, such as activation of NTKs.</p

Potential impact of invasive alien species on ecosystem services provided by a tropical forested ecosystem: a case study from Montserrat

Local stakeholders at the important but vulnerable Centre Hills on Montserrat consider that the continued presence of feral livestock (particularly goats and pigs) may lead to widespread replacement of the reserve’s native vegetation by invasive alien trees (Java plum and guava), and consequent negative impacts on native animal species. Since 2009, a hunting programme to control the feral livestock has been in operation. However long-term funding is not assured. Here, we estimate the effect of feral livestock control on ecosystem services provided by the forest to evaluate whether the biodiversity conservation rationale for continuation of the control programme is supported by an economic case. A new practical tool (Toolkit for Ecosystem Service Site-based Assessment) was employed to measure and compare ecosystem service provision between two states of the reserve (i.e. presence and absence of feral livestock control) to estimate the net consequences of the hunting programme on ecosystem services provided by the forest. Based on this we estimate that cessation of feral livestock management would substantially reduce the net benefits provided by the site, including a 46 % reduction in nature-based tourism (from $419,000 to$228,000) and 36 % reduction in harvested wild meat (from $205,000 to$132,000). The overall net benefit generated from annual ecosystem service flows associated with livestock control in thereserve, minus the management cost, was $214,000 per year. We conclude that continued feral livestock control is important for maintaining the current level of ecosystem services provided by the reserve

Deep Brain Stimulation of Nucleus Accumbens Region in Alcoholism Affects Reward Processing

The influence of bilateral deep brain stimulation (DBS) of the nucleus nucleus (NAcc) on the processing of reward in a gambling paradigm was investigated using H2[15O]-PET (positron emission tomography) in a 38-year-old man treated for severe alcohol addiction. Behavioral data analysis revealed a less risky, more careful choice behavior under active DBS compared to DBS switched off. PET showed win- and loss-related activations in the paracingulate cortex, temporal poles, precuneus and hippocampus under active DBS, brain areas that have been implicated in action monitoring and behavioral control. Except for the temporal pole these activations were not seen when DBS was deactivated. These findings suggest that DBS of the NAcc may act partially by improving behavioral control