An investigation into aripiprazole's partial D(2) agonist effects within the dorsolateral prefrontal cortex during working memory in healthy volunteers

Rationale: Working memory impairments in schizophrenia have been attributed to dysfunction of the dorsolateral prefrontal cortex (DLPFC) which in turn may be due to low DLPFC dopamine innervation. Conventional antipsychotic drugs block DLPFC D2 receptors, and this may lead to further dysfunction and working memory impairments. Aripiprazole is a D2 receptor partial agonist hypothesised to enhance PFC dopamine functioning, possibly improving working memory. Objectives: We probed the implications of the partial D2 receptor agonist actions of aripiprazole within the DLPFC during working memory. Investigations were carried out in healthy volunteers to eliminate confounds of illness or medication status. Aripiprazole’s prefrontal actions were compared with the D2/5-HT2A blocker risperidone to separate aripiprazole’s unique prefrontal D2 agonist actions from its serotinergic and striatal D2 actions that it shares with risperidone. Method: A double-blind, placebo-controlled, parallel design was implemented. Participants received a single dose of either 5 mg aripiprazole, 1 mg risperidone or placebo before performing the n-back task whilst undergoing fMRI scanning. Results: Compared with placebo, the aripiprazole group demonstrated enhanced DLPFC activation associated with a trend for improved discriminability (d’) and speeded reaction times. In contrast to aripiprazole’s neural effects, the risperidone group demonstrated a trend for reduced DLPFC recruitment. Unexpectedly, the risperidone group demonstrated similar effects to aripiprazole on d’ and additionally had reduced errors of commission compared with placebo. Conclusion: Aripiprazole has unique DLPFC actions attributed to its prefrontal D2 agonist action. Risperidone’s serotinergic action that results in prefrontal dopamine release may have protected against any impairing effects of its prefrontal D2 blockade

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Familial association of pancreatic cancer with other malignancies in Swedish families

BACKGROUND: The aim of this study was to characterise the familial association of pancreatic cancer with other malignancies. METHODS: Relative risks (RRs) of pancreatic cancer according to family history of cancer were calculated using the updated Swedish Family-Cancer Database, which includes over 11.5 million individuals. Estimates were based on Poisson regression. RRs of tumours for individuals with a parental history of pancreatic cancer were also estimated. RESULTS: The risk of pancreatic cancer was elevated in individuals with a parental history of cancers of the liver (RR 1.41; 95% CI 1.10-1.81), kidney (RR 1.37; 95% CI 1.06-1.76), lung (RR 1.50; 95% CI 1.27-1.79) and larynx (RR 1.98; 95% CI 1.19-3.28). Associations were also found between parental history of pancreatic cancer and cancers of the small intestine, colon, breast, lung, testis and cervix in offspring. There was an increased risk of pancreatic cancer associated with early-onset breast cancer in siblings. CONCLUSION: Pancreatic cancer aggregates in families with several types of cancer. Smoking may contribute to the familial aggregation of pancreatic and lung tumours, and the familial clustering of pancreatic and breast cancer could be partially explained by inherited mutations in the BRCA2 gene. British Journal of Cancer (2009) 101, 1792-1797. doi: 10.1038/sj.bjc.6605363 www.bjcancer.com Published online 13 October 2009 (C) 2009 Cancer Research U

Design of a multicentered randomized controlled trial on the clinical and cost effectiveness of schema therapy for personality disorders

<p>Abstract</p> <p>Background</p> <p>Despite international guidelines describing psychotherapy as first choice for people with personality disorders (PDs), well-designed research on the effectiveness and cost-effectiveness of psychotherapy for PD is scarce. Schema therapy (ST) is a specific form of psychological treatment that proved to be effective for borderline PD. Randomized controlled studies on the effectiveness of ST for other PDs are lacking. Another not yet tested new specialized treatment is Clarification Oriented Psychotherapy (COP). The aim of this project is to perform an effectiveness study as well as an economic evaluation study (cost effectiveness as well as cost-utility) comparing ST versus COP versus treatment as usual (TAU). In this study, we focus on avoidant, dependent, obsessive-compulsive, paranoid, histrionic and narcissistic PD.</p> <p>Methods/Design</p> <p>In a multicentered randomized controlled trial, ST, and COP as an extra experimental condition, are compared to TAU. Minimal 300 patients are recruited in 12 mental health institutes throughout the Netherlands, and receive an extensive screening prior to enrolment in the study. When eligible, they are randomly assigned to one of the intervention groups. An economic evaluation and a qualitative research study on patient and therapist perspectives on ST are embedded in this trial. Outcome assessments (both for clinical effectiveness and economic evaluation) take place at 6,12,18,24 and 36 months after start of treatment. Primary outcome is recovery from PD; secondary measures include general psychopathological complaints, social functioning and quality of life. Data for the cost-effectiveness and cost-utility analyses are collected by using a retrospective cost interview. Information on patient and therapist perspectives is gathered using in-depth interviews and focus groups, and focuses on possible helpful and impeding aspects of ST.</p> <p>Discussion</p> <p>This trial is the first to compare ST and COP head-to-head with TAU for people with a cluster C, paranoid, histrionic and/or narcissistic PD. By combining clinical effectiveness data with an economic evaluation and with direct information from primary stakeholders, this trial offers a complete and thorough view on ST as a contribution to the improvement of treatment for this PD patient group.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=566">NTR566</a></p

Desire and Dread from the Nucleus Accumbens: Cortical Glutamate and Subcortical GABA Differentially Generate Motivation and Hedonic Impact in the Rat

Background: GABAergic signals to the nucleus accumbens (NAc) shell arise from predominantly subcortical sources whereas glutamatergic signals arise mainly from cortical-related sources. Here we contrasted GABAergic and glutamatergic generation of hedonics versus motivation processes, as a proxy for comparing subcortical and cortical controls of emotion. Local disruptions of either signals in medial shell of NAc generate intense motivated behaviors corresponding to desire and/or dread, along a rostrocaudal gradient. GABA or glutamate disruptions in rostral shell generate appetitive motivation whereas disruptions in caudal shell elicit fearful motivation. However, GABA and glutamate signals in NAc differ in important ways, despite the similarity of their rostrocaudal motivation gradients. Methodology/Principal Findings: Microinjections of a GABAA agonist (muscimol), or of a glutamate AMPA antagonist (DNQX) in medial shell of rats were assessed for generation of hedonic ‘‘liking’ ’ or ‘‘disliking’ ’ by measuring orofacial affective reactions to sucrose-quinine taste. Motivation generation was independently assessed measuring effects on eating versus natural defensive behaviors. For GABAergic microinjections, we found that the desire-dread motivation gradient was mirrored by an equivalent hedonic gradient that amplified affective taste ‘‘liking’ ’ (at rostral sites) versus ‘‘disliking’ ’ (at caudal sites). However, manipulation of glutamatergic signals completely failed to alter pleasure-displeasure reactions to sensory hedonic impact, despite producing a strong rostrocaudal gradient of motivation

A Rapid, Strong, and Convergent Genetic Response to Urban Habitat Fragmentation in Four Divergent and Widespread Vertebrates

Urbanization is a major cause of habitat fragmentation worldwide. Ecological and conservation theory predicts many potential impacts of habitat fragmentation on natural populations, including genetic impacts. Habitat fragmentation by urbanization causes populations of animals and plants to be isolated in patches of suitable habitat that are surrounded by non-native vegetation or severely altered vegetation, asphalt, concrete, and human structures. This can lead to genetic divergence between patches and in turn to decreased genetic diversity within patches through genetic drift and inbreeding.We examined population genetic patterns using microsatellites in four common vertebrate species, three lizards and one bird, in highly fragmented urban southern California. Despite significant phylogenetic, ecological, and mobility differences between these species, all four showed similar and significant reductions in gene flow over relatively short geographic and temporal scales. For all four species, the greatest genetic divergence was found where development was oldest and most intensive. All four animals also showed significant reduction in gene flow associated with intervening roads and freeways, the degree of patch isolation, and the time since isolation.Despite wide acceptance of the idea in principle, evidence of significant population genetic changes associated with fragmentation at small spatial and temporal scales has been rare, even in smaller terrestrial vertebrates, and especially for birds. Given the striking pattern of similar and rapid effects across four common and widespread species, including a volant bird, intense urbanization may represent the most severe form of fragmentation, with minimal effective movement through the urban matrix

Global Diversity of Ascidiacea

The class Ascidiacea presents fundamental opportunities for research in the fields of development, evolution, ecology, natural products and more. This review provides a comprehensive overview of the current knowledge regarding the global biodiversity of the class Ascidiacea, focusing in their taxonomy, main regions of biodiversity, and distribution patterns. Based on analysis of the literature and the species registered in the online World Register of Marine Species, we assembled a list of 2815 described species. The highest number of species and families is found in the order Aplousobranchia. Didemnidae and Styelidae families have the highest number of species with more than 500 within each group. Sixty percent of described species are colonial. Species richness is highest in tropical regions, where colonial species predominate. In higher latitudes solitary species gradually contribute more to the total species richness. We emphasize the strong association between species richness and sampling efforts, and discuss the risks of invasive species. Our inventory is certainly incomplete as the ascidian fauna in many areas around the world is relatively poorly known, and many new species continue to be discovered and described each year

Correction to: Progressive subcortical volume loss in treatment-resistant schizophrenia patients after commencing clozapine treatment.

Correction to: Neuropsychopharmacology https://doi.org/10.1038/s41386-020-0665-4 Linked to BURO article https://eprints.bournemouth.ac.uk/34082

Developing a decision tool to identify patients with personality disorders in need of highly specialized care

Background: Current guidelines recommend referral to highly specialized care for patients with severe personality disorders. However, criteria for allocation to highly specialized care are not clearly defined. The aim of the presentstudy was to develop a decision tool that can support clinicians to identify patients with a personality disorder in need of highly specialized care.Methods: Steps taken to develop a decision tool were a literature search, concept mapping, a meeting with experts and a validation study.Results: The concept mapping method resulted in six criteria for the decision tool. The model used in concept mapping provided a good fit (stress value = 0.30) and reasonable reliability (ρ = 0.49). The bridging values were low, indicating homogeneity. The decision tool was subsequently validated by enrolling 368 patients from seven centers. A multilevel model with a Receiver Operating Characteristic Curve (ROC) was applied. In this way, an easily implementable decision tool with relatively high sensitivity (0.74) and specificity (0.69) was developed.Conclusions: A decision tool to identify patients with personality disorders for highly specialized care was developed using advanced methods to combine the input of experts with currently available scientific knowledge. The tool appeared to be able to accurately identify this group of patients. Clinicians can use this decision tool to identify patients who are in need of highly specialized treatment