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Cognitive behavioural therapy (CBT) is an important treatment in conjunction with psychopharmacotherapy in schizophrenia. However, there is only very little research on the effects of such interventions on brain function.
Recent studies have suggested that jumping to conclusions and a specific attributional bias is a predominant cognitive style in patients which might lead to the development of delusions. In this multi-centre fMRI trial, we investigated the effect of nine months of CBT on neural correlates of “jumping to conclusions” and the “attributional style” in patients with psychosis. Eighty patients and 80 control subjects were recruited in six centres and measured with 3-Tesla functional magnetic imaging (fMRI) before and after CBT.
It could be shown that CBT ameliorates differences in brain activations between patients and controls after nine months.
These results support the feasibility of fMRI multicenter trials and sheds further light into the mechanisms relating psychotherapy to brain function in Schizophrenia.
There is evidence that patients with persecutory delusions tend to attribute excessively hypothetical positive events to internal causes and hypothetical negative events to external causes, arrive at hasty conclusions and fail in gathering and assessing adequate feedback, particularly when emotionally salient material is involved. Research on the neural correlates of the corresponding neural correlates and even more so on the potential effects of cognitive behavioral therapy (CBT) on the associated cerebral networks is almost unavailable.
The first and preliminary results of a multicentre fMRI study will be presented.
In this study eighty schizophrenia patients from the POSITIVE clinical trial and eighty healthy subjects were recruited at six German university hospitals (Bonn, Duisburg-Essen, Düsseldorf, Frankfurt, Cologne, Tubingen). After nine months of therapy (either with CBT or Supportive Therapy) patients and controls were re-examined enabling the study correlates of cerebral reorganization processes.
We found reliable differences in brain activation relating to phenomena of decision making under uncertainty, and biased attribution (self- vs. external reference of emotional events).
The comparison of both groups revealed significant decreased activation in key areas for decision making, self-reflection, self-relevance and agency attribution of patients with schizophrenia.
The preliminary data analysis of the still blinded treatment arms shows significantly increased activations in these areas after nine months of CBT. This suggest neuroplasitic changes according to relearning strategies in psychotic patients with schizophrenia and will hopefully give rise to a more widespread application of CBT in treatment of schizophrenia.
This case report describes a patient on tranylcypromine who erroneously received a single dose of imipramine and subsequently developed a fatal serotonin syndrome. Both the clinical features and the pathophysiology of the serotonin syndrome are discussed.
Pedophilia is a disorder where sexual preferences of adults are directed towards children. This disorder impacts society with 1–2 out of every 10 children being sexually approached by an adult, often resulting in prolonged negative psychological effects. Prior research reported structural and functional amygdala alterations in pedophilia. As the neurophenomenological model of sexual arousal suggests the importance of the amygdala in the emotional component, we focused on amygdala functional connectivity in pedophilia.
To investigate amygdala functional connectivity (FC) modulated by expectancy and salient stimuli in pedophilic patients.
Thirteen pedophilic patients and 13 matched healthy controls underwent a salience expectancy task in a 7T ultra high fMRI study. Subjects perceived pictures of naked adults and children. Half of the pictures were preceded by an expectancy cue. Participants were instructed to actively expect the picture depending on the cue. We conducted psychophysiological analysis (PPI) to examine amygdala FC changes in two amygdala sub-regions for child/adult stimuli during the expectancy period and the visual stimuli consummation period using as seed regions the basolateral (BLA) and central nucleus of the amygdala (CeA).
Healthy controls, relative to patients showed significant stronger left CeA to right post-central gyrus FC during expectancy of adult > child picture. For picture condition (adult > child picture) we found significant stronger left CeA to left dorsolateral prefrontal cortex FC in patients compared to healthy controls.
These findings add to the recent literature by indicating that amygdala dysfunctional connectivity is involved in development of deviant sexual behavior.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The development and maintenance of an alcohol addiction is a complex interaction between genetic and environmental factors. Genetic effects seem to contribute substantially to the risk of developing an addiction, but also to its course and patients’ responses to different treatments. Recent studies identified associations between polymorphisms in the genes of glutamate and μ-opioid receptors and addiction risk. Those receptors are of special interest, because they are targets of therapeutic agents, such as acamprosate and topiramate.
Objectives and aims
Several studies were conducted, in order to further determine the effects of genetic polymorphisms in glutamate and opioid receptor genes on addictive behavior, neural response to alcohol cues and relapse risk.
Genetic effects were investigated in samples of alcohol-dependent patients using functional imaging techniques, neuropsychological tests and follow-up investigation after standard clinical treatment. Data on clinical parameters, neuronal response to alcohol cues, functional neuronal connectivity and relapse risk were collected and analyzed.
Results demonstrate effects of genetic polymorphisms in glutamate and opioid receptors on neuronal response to alcohol cues in frontal and mesolimbic brain areas, subjective craving and time to first relapse. Current findings will be discussed in the light of existing evidence on the contribution of genetic effects to treatment outcome and patient stratification.
The investigation of genetic risk factors and mechanisms by which they affect addiction related phenotypes seems to be a promising tool to identify molecular treatment targets and predictors for successful treatment strategies.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Cardiovascular risk prediction tools are important for cardiovascular disease (CVD) prevention, however, which algorithms are appropriate for people with severe mental illness (SMI) is unclear.
To determine the cost-effectiveness using the net monetary benefit (NMB) approach of two bespoke SMI-specific risk algorithms compared to standard risk algorithms for primary CVD prevention in those with SMI, from an NHS perspective.
A microsimulation model was populated with 1000 individuals with SMI from The Health Improvement Network Database, aged 30–74 years without CVD. Four cardiovascular risk algorithms were assessed; (1) general population lipid, (2) general population BMI, (3) SMI-specific lipid and (4) SMI-specific BMI, compared against no algorithm. At baseline, each cardiovascular risk algorithm was applied and those high-risk (> 10%) were assumed to be prescribed statin therapy, others received usual care. Individuals entered the model in a ‘healthy’ free of CVD health state and with each year could retain their current health state, have cardiovascular events (non-fatal/fatal) or die from other causes according to transition probabilities.
The SMI-specific BMI and general population lipid algorithms had the highest NMB of the four algorithms resulting in 12 additional QALYs and a cost saving of approximately £37,000 (US$ 58,000) per 1000 patients with SMI over 10 years.
The general population lipid and SMI-specific BMI algorithms performed equally well. The ease and acceptability of use of a SMI-specific BMI algorithm (blood tests not required) makes it an attractive algorithm to implement in clinical settings.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Alcohol relapse is often occurring to regulate negative affect during withdrawal. On the neurobiological level, alcoholism is associated with gray matter (GM) abnormalities in regions that regulate emotional experience such as the orbitofrontal cortex (OFC). However, no study to our knowledge has investigated the neurobiological unpinning of affect in alcoholism at early withdrawal and the associations of OFC volume with long-term relapse risk.
One hundred and eighty-two participants were included, 95 recently detoxified alcohol dependent patients (ADP) and 87 healthy controls (HC). We measured affective states using the positive and negative affect schedule (PANAS). We collected T1-weighted brain structural images and performed Voxel-based morphometry (VBM).
Findings revealed GM volume decrease in alcoholics in the prefrontal cortex (including medial OFC), anterior cingulate gyrus, and insula. GM volume in the medial OFC was positively associated with NA in the ADP group. Cox regression analysis predicted that risk to heavy relapse at 6 months increases with decreased GM volume in the medial OFC.
Negative affect during alcohol withdrawal was positively associated with OFC volume. What is more, increased GM volume in the OFC also moderated risk to heavy relapse at 6 months. Reduced GM in the OFC poses as risk to recovery from alcohol dependence and provides valuable insights into transient negative affect states during withdrawal that can trigger relapse. Implications exist for therapeutic interventions signifying the OFC as a neurobiological marker to relapse and could explain the inability of ADP to regulate internal negative affective states.
When open-cut mines are eventually abandoned, they leave a large hole with sloping sides. The hole fills with rain water, and there is also contaminated run-off from surrounding land, that moves through the rock and eventually through the sloping sides of the abandoned mine. This paper considers a two-dimensional unsteady model motivated by this leaching flow through the rock and into the rain-water reservoir. The stability of the interface between the two fluids is analysed in the inviscid limit. A viscous Boussinesq model is also presented, and a closed-form solution is presented to this problem, after it has been linearized in a manner consistent with Boussinesq theory. That solution suggests that the interfacial zone is effectively neutrally stable as it evolves in time. However, an asymptotic theory in the interfacial region shows the interface to be unstable. In addition, the nonlinear Boussinesq model is solved using a spectral method. Interfacial travelling waves and roll-up are observed and discussed, and compared against the predictions of asymptotic Boussinesq theory.
Mental disorders can have a major impact on brain development. Peripheral blood concentrations of brain-derived neurotrophic factor (BDNF) are lower in adult psychiatric disorders. Serum BDNF concentrations and BDNF genotype have been associated with cortical maturation in children and adolescents. In 2 large independent samples, this study tests associations between serum BDNF concentrations, brain structure, and psychopathology, and the effects of BDNF genotype on BDNF serum concentrations in late childhood and early adolescence.
Children and adolescents (7-14 years old) from 2 cities (n = 267 in Porto Alegre; n = 273 in São Paulo) were evaluated as part of the Brazilian high-risk cohort (HRC) study. Serum BDNF concentrations were quantified by sandwich ELISA. Genotyping was conducted from blood or saliva samples using the SNParray Infinium HumanCore Array BeadChip. Subcortical volumes and cortical thickness were quantified using FreeSurfer. The Development and Well-Being Behavior Assessment was used to identify the presence of a psychiatric disorder.
Serum BDNF concentrations were not associated with subcortical volumes or with cortical thickness. Serum BDNF concentration did not differ between participants with and without mental disorders, or between Val homozygotes and Met carriers.
No evidence was found to support serum BDNF concentrations as a useful marker of developmental differences in brain and behavior in early life. Negative findings were replicated in 2 of the largest independent samples investigated to date.
Rayleigh–Taylor instability occurs when a heavier fluid overlies a lighter fluid, and the two seek to exchange positions under the effect of gravity. We present a linearized theory for arbitrary three-dimensional (3D) initial disturbances that grow in time, and calculate the evolution of the interface for early times. A new spectral method is introduced for the fully 3D nonlinear problem in a Boussinesq fluid, where the interface between the light and heavy fluids is approximated with a smooth but rapid density change in the fluid. The results of large-scale numerical calculation are presented in fully 3D geometry, and compared and contrasted with the early-time linearized theory.
Species distribution models (SDMs) are statistical tools used to develop continuous predictions of species occurrence. ‘Integrated SDMs’ (ISDMs) are an elaboration of this approach with potential advantages that allow for the dual use of opportunistically collected presence-only data and site-occupancy data from planned surveys. These models also account for survey bias and imperfect detection through the use of a hierarchical modelling framework that separately estimates the species–environment response and detection process. This is particularly helpful for conservation applications and predictions for rare species, where data are often limited and prediction errors may have significant management consequences. Despite this potential importance, ISDMs remain largely untested under a variety of scenarios. We performed an exploration of key modelling decisions and assumptions on an ISDM using the endangered Baird’s tapir (Tapirus bairdii) as a test species. We found that site area had the strongest effect on the magnitude of population estimates and underlying intensity surface and was driven by estimates of model intercepts. Selecting a site area that accounted for the individual movements of the species within an average home range led to population estimates that coincided with expert estimates. ISDMs that do not account for the individual movements of species will likely lead to less accurate estimates of species intensity (number of individuals per unit area) and thus overall population estimates. This bias could be severe and highly detrimental to conservation actions if uninformed ISDMs are used to estimate global populations of threatened and data-deficient species, particularly those that lack natural history and movement information. However, the ISDM was consistently the most accurate model compared to other approaches, which demonstrates the importance of this new modelling framework and the ability to combine opportunistic data with systematic survey data. Thus, we recommend researchers use ISDMs with conservative movement information when estimating population sizes of rare and data-deficient species. ISDMs could be improved by using a similar parameterization to spatial capture–recapture models that explicitly incorporate animal movement as a model parameter, which would further remove the need for spatial subsampling prior to implementation.
We consider fluid in a channel of finite height. There is a circular hole in the channel bottom, through which fluid of a lower density is injected and rises to form a plume. Viscous boundary layers close to the top and bottom of the channel are assumed to be so thin that the viscous fluid effectively slips along each of these boundaries. The problem is solved using a novel spectral method, in which Hankel transforms are first used to create a steady-state axisymmetric (inviscid) background flow that exactly satisfies the boundary conditions. A viscous correction is then added, so as to satisfy the time-dependent Boussinesq Navier–Stokes equations within the fluid, leaving the boundary conditions intact. Results are presented for the “lazy” plume, in which the fluid rises due only to its own buoyancy, and we study in detail its evolution with time to form an overturning structure. Some results for momentum-driven plumes are also presented, and the effect of the upper wall of the channel on the evolution of the axisymmetric plume is discussed.
The coastal waters of east Lewis from the Butt of Lewis to Loch Erisort are a proposed Marine Protected Area (MPA) for Risso's dolphins (Grampus griseus). A total of 100.4 h (2006.4 km) of active search effort (Beaufort sea states ≤3) was collected during 72 dedicated boat surveys between 2010 and 2017 (primarily in August and September) in the southern part of the MPA and south to the Shiant Isles. Forty Risso's dolphin sightings and 24.1 h of encounter effort were recorded, predominantly along the southern and eastern Eye Peninsula in 20–40 m water depths and at distances <1 km from shore. Group size ranged from one to 50 animals (mean = 11.8 dolphins) and calves occurred in 37.5% of sightings. A total of 2404 shore-based scans (Beaufort sea states ≤3) carried out from Tiumpan Head between September 2011 and December 2017 resulted in 271 (11.3%) ‘dolphin-present’ scans. Dolphins were present year-round, with a seasonal increase between May and October. ‘Calf-present’ scans only occurred between April and October. Photo-identification images from 28 boat surveys produced a minimum population size of 117 animals. There was evidence of high inter- and intra-annual site fidelity, with individual dolphins photographically captured in up to six of the eight survey years, and between two and seven capture dates being recorded for over 45% of individuals within most years. The combined datasets support the importance of east Lewis for Risso's dolphins, and recommendations are made for ongoing monitoring of dolphin occurrence throughout the wider MPA.
The consumption of nitrate-rich vegetables can acutely lower blood pressure and improve mediators shown to optimise vascular health. However, we do not yet understand the impact of long-term habitual dietary nitrate intake and its association with CVD. Therefore, the aim of this investigation was to examine the relationship between habitual dietary nitrate intakes and risk of CHD in women from the Nurses’ Health Study. We prospectively followed 62 535 women who were free from diabetes, CVD and cancer at baseline in 1986. Information on diet was updated every 4 years with validated FFQ. The main outcome was CHD defined by the occurrence of non-fatal myocardial infarction or fatal CHD. Cox proportional hazard regression models were used to estimate the relative risks (RR) and 95 % CI. During 26 years of follow-up, 2257 cases of CHD were identified. When comparing the highest quintile of nitrate intake with the lowest quintile, in aged-adjusted analysis there was a protective association for CHD (RR=0·77, 95 % CI 0·68, 0·97; P=0·0002) which dissipated after further adjustment for smoking, physical activity, BMI and race (RR=0·91; 95 % CI 0·80, 1·04; P=0·27). This magnitude of association was further attenuated once we adjusted for the Alternative Healthy Eating Index excluding vegetable and fruit consumption (RR=1·04, 95 % CI 0·91, 1·20; P=0·34). Dietary nitrate intake was not related to the risk of CHD after adjustment for other lifestyle and non-vegetable dietary factors in a large group of US women.
Crevasses and englacial fracture networks route meltwater from a glacier's surface to the subglacial drainage system and thus influence glacial hydraulics. However, rapid fracture growth may also lead to sudden and potentially hazardous structural failure of unstable glaciers and ice dams, rifting of ice shelves, or iceberg calving. Here, we use passive seismic recordings to investigate the englacial fracture network on Glacier de la Plaine Morte, Switzerland. Glacier dynamics and the drainage of an ice-marginal lake give rise to numerous icequakes, the majority of which generate dispersed, high-frequency Rayleigh waves. A wide distribution of events allows us to study azimuthal anisotropy between 10 and 30 Hz in order to extract englacial seismic velocities in regions of preferentially oriented crevasses. Beamforming applied to a 100-m-aperture array reveals azimuthal anisotropy of Rayleigh-wave phase velocities reaching a strength of 8% at high frequencies. In addition, we find that the fast direction of wave propagation coincides with the observed surface strike of the narrow crevasses. Forward modeling and inversion of dispersion curves suggest that the azimuthal anisotropy is induced by a 40-m-thick crevassed layer at the surface of the glacier with 8% anisotropy in shear-wave velocity.
Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders.
We assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia.
Heritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50.
Given the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.
Self-screening using an electronic version of the Malnutrition Universal Screening Tool (‘MUST’) has been developed but its implementation requires investigation. A total of 100 outpatients (mean age 50 (sd 16) years; 57 % male) self-screened with an electronic version of ‘MUST’ and were then screened by a healthcare professional (HCP) to assess concurrent validity. Ease of use, time to self-screen and prevalence of malnutrition were also assessed. A further twenty outpatients (mean age 54 (sd 15) years; 55 % male) examined preference between self- screening with paper and electronic versions of ‘MUST’. For the three-category classification of ‘MUST’ (low, medium and high risk), agreement between electronic self-screening and HCP screening was 94 % (κ=0·74, se 0·092; P<0·001). For the two-category classification (low risk; medium+high risk) agreement was 96 % (κ=0·82, se 0·085; P<0·001), comparable with the previously reported paper-based self-screening. In all, 15 % of patients categorised themselves ‘at risk’ of malnutrition (5 % medium, 10 % high). Electronic self-screening took 3 min (sd 1·2 min), 40 % faster than previously reported for the paper-based version. Patients found the tool easy or very easy to understand (99 %) and complete (98 %). Patients that assessed both tools found the electronic tool easier to complete (65 %) and preferred it (55 %) to the paper version. Electronic self-screening using ‘MUST’ in a heterogeneous group of hospital outpatients is acceptable, user-friendly and has ‘substantial to almost-perfect’ agreement with HCP screening. The electronic format appears to be as agreeable and often the preferred format when compared with the validated paper-based ‘MUST’ self-screening tool.
OBJECTIVES/SPECIFIC AIMS: We sought to investigate the role of the host microbiome during severe, acute respiratory infection (ARI) to understand the drivers of both acute clinical pathogenesis. METHODS/STUDY POPULATION: Nasopharyngeal swabs comprised of mixed cell populations at the active site of infection were collected from 192 hospitalized pediatric patients with ARI. We combined comprehensive respiratory virus detection and virus genome sequencing with 16S rRNA gene sequencing to evaluate the microbial content of the airway during ARI. This data was coupled with 11 clinical parameters, which were compiled to create a clinical severity score. The microbiome profiles were assessed to determine if clinical severity of infection, and/or specific virus was associated with increased clinical severity. RESULTS/ANTICIPATED RESULTS: We identified 8 major microbiome profiles classified by dominant bacterial genus, Moraxella, Corynebacterium, Staphylococcus, Haemophilus, Streptococcus, Alloiococcus, Schlegelella, and Diverse. Increased clinical severity was significantly associated with microbiome profiles dominated by Haemophilus, Streptococcus, and Schlegelella, whereas Corynebacterium and Alloiococcus were more prevalent in children with less severe disease. Independent of the microbial community, more than 60% of patients with the highest clinical severity were infected with either respiratory syncytial virus or rhinovirus. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results indicate that individually and in combination, both virus and microbial composition may drive clinical severity during acute respiratory viral infections. It is still unclear how the complex interplay between virus, bacterial community, and the host response influence long-term respiratory impacts, such as the development of asthma. Nonetheless, during ARIs therapeutic interventions such as antibiotics and probiotics may be warranted in a subset of patients that are identified to have both a virus and microbiome profile that is associated with increased pathogenesis to limit both acute and long-term phenotypes.