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Recent studies have identified DAAO as a probable susceptibility gene for schizophrenia and bipolar disorder. However, little is known about how this gene may affect brain function to increase vulnerability to these disorders.
The present investigation examined the impact of DAAO genotype on brain function in patients with schizophrenia, patients with bipolar I disorder and healthy volunteers.
We tested the hypotheses that the high-risk variant of DAAO would be associated with altered prefrontal function and functional connectivity in schizophrenic and bipolar patients.
We used functional magnetic resonance imaging to measure brain responses during a verbal fluency task in a total of 121 subjects comprising 40 patients with schizophrenia, 33 patients with bipolar I disorder and 48 healthy volunteers. We then used statistical parametric mapping (SPM) and psycho-physiological interaction (PPI) analyses to estimate the main effects of diagnostic group, the main effect of genotype and their interaction on brain activation and functional connectivity.
In schizophrenic patients relative to bipolar patients and controls, the high-risk variant of DAAO was associated with lower deactivation in the left precuneus and greater activation in the right calcarine and posterior cingulate gyrus during task performance. In addiction, these areas expressed altered functional connectivity with the rest of the brain in schizophrenic patients relative to bipolar patients and controls.
Our results suggest that genetic variation in DAAO has a significant impact on brain function and provide preliminary evidence for a disease-specific pattern of gene action in specific brain regions.
To examine the effect of a polymorphism in the Dopamine Transporter (DAT) gene on brain activation during executive function and, for the first time:
1. determine the extent to which this is altered in schizophrenia and
2. use a verbal fluency paradigm.
This is relevant since:
1. DAT plays a key role in the regulation of dopamine, which modulates cortical activation during cognitive tasks and
2. a disruption of dopamine function is a fundamental pathophysiological feature of schizophrenia.
Functional magnetic resonance imaging was used to measure whole-brain responses during overt verbal fluency in 85 subjects: 44 healthy volunteers and 41 DSM-IV schizophrenia patients. Main effects of genotype and diagnostic group on activation and their interaction were estimated using an ANOVA in SPM5.
The 10-repeat allele of the 3'UTR VNTR was associated with greater activation than the 9-repeat allele in the left (Z=4.8; FWEp=0.005) and right (Z=4.2; FWEp=0.057) anterior insula and with decreased activation in the rostral anterior cingulate (Z=4.3 FWEp=0.04) during word generation (versus baseline). These effects were irrespective of diagnostic group but generally more marked in patients. There were also strong trends for groupxgenotype interactions in the left middle frontal gyrus and the left nucleus accumbens. Analysis was controlled for task performance, IQ, antipsychotic medication, psychopathology and demographics.
Cortical function during executive tasks is normally modulated by variation in the DAT gene, effect which is dependent on the brain region. DAT's effect may be altered in schizophrenia patients, which may reflect altered central dopamine function.
Akathisia remains a challenge in routine psychiatric practice, despite the widespread use of second generation antipsychotics (SGAs). This analysis was performed to quantify and qualify clinical characteristics of akathisia in schizophrenia or schizoaffective disorder patients experiencing an acute relapse who were randomized to receive aripiprazole, or placebo in 5 pooled short term trials.
A post hoc analysis of the safety dataset was conducted to assess clinical aspects of akathisia in five 4- or 6-week, double-blind, randomized trials comparing aripiprazole (2, 5, 10, 15, 20, 30 mg/day) to placebo.
A total of 1,635 patients was included in this analysis (aripiprazole: n=1170; placebo: n=465). Akathisia was reported by 9% of the aripiprazole-treated patients and 6% of those receiving placebo. Among those reporting akathisia, more patients receiving aripiprazole (83%, n=86) reported this AE within the first 2 weeks of the trials when compared to placebo (69%, n=20). The mean and median duration of akathisia was generally low in both groups (Mean: aripiprazole=12.5 days and placebo=4.2 days; Median, aripiprazole=5.0 days and placebo=1.5 days). The percentage of patients reporting akathisia at endpoint (BARS Item 4≥2) was similar between aripiprazole- (16%) and placebo-treated patients (14%).
In the aripiprazole and placebo groups, akathisia appeared to occur early in treatment, was time-limited, and was associated with high rates of concomitant benzodiazepine usage. Additionally, most cases of akathisia were reported as mild to moderate and rarely associated with treatment discontinuation.
The heritability of the brain’s structure and function in schizophrenia remains elusive
To assess the influence of genetic and environmental factors on executive function in schizophrenia.
A twin-sibling study of 206 subjects; 163 twins, varying in their zygosity and concordance for schizophrenia, and 43 singletons from sibling clusters varying in their concordance for schizophrenia. We assessed performance and regional brain activation using functional magnetic resonance imaging, during a phonological verbal fluency task.
Patients and their unaffected relatives developed greater activation in the left inferior frontal gyrus, and greater deactivation in the middle temporal gyri bilaterally. These features were maximally evident in subjects with schizophrenia. When the analysis was restricted to the unaffected relatives and healthy controls, a similar pattern was evident. Heritability was greatest in the left hippocampus and the right middle temporal gyrus. Genetic modelling indicated a phenotypic correlation between schizophrenia and increased activity in the inferior frontal gyrus and reduced activity in the left middle temporal gyrus and left hippocampus, which appeared principally due to shared genetic effects.
Both schizophrenia and its familial vulnerability were associated with altered frontal, parahippocampal and temporal activation during verbal fluency. The altered left inferior frontal activity was particularly associated with schizophrenia, while altered left medial temporal and right middle temporal activity were more heritable. The latter was more intimately linked to the genetic risk for schizophrenia, and thus the better candidate intermediate phenotype.
A pilot study by 6 Clinical and Translational Science Awards (CTSAs) explored how bibliometrics can be used to assess research influence.
Evaluators from 6 institutions shared data on publications (4202 total) they supported, and conducted a combined analysis with state-of-the-art tools. This paper presents selected results based on the tools from 2 widely used vendors for bibliometrics: Thomson Reuters and Elsevier.
Both vendors located a high percentage of publications within their proprietary databases (>90%) and provided similar but not equivalent bibliometrics for estimating productivity (number of publications) and influence (citation rates, percentage of papers in the top 10% of citations, observed citations relative to expected citations). A recently available bibliometric from the National Institutes of Health Office of Portfolio Analysis, examined after the initial analysis, showed tremendous potential for use in the CTSA context.
Despite challenges in making cross-CTSA comparisons, bibliometrics can enhance our understanding of the value of CTSA-supported clinical and translational research.
Diagnostic errors can have tremendous consequences because they can result in a fatal chain of wrong decisions. Experts assume that physicians' desire to confirm a preliminary diagnosis while failing to seek contradictory evidence is an important reason for wrong diagnoses. This tendency is called ‘confirmation bias’.
To study whether psychiatrists and medical students are prone to confirmation bias and whether confirmation bias leads to poor diagnostic accuracy in psychiatry, we presented an experimental decision task to 75 psychiatrists and 75 medical students.
A total of 13% of psychiatrists and 25% of students showed confirmation bias when searching for new information after having made a preliminary diagnosis. Participants conducting a confirmatory information search were significantly less likely to make the correct diagnosis compared to participants searching in a disconfirmatory or balanced way [multiple logistic regression: odds ratio (OR) 7.3, 95% confidence interval (CI) 2.53–21.22, p<0.001; OR 3.2, 95% CI 1.23–8.56, p=0.02]. Psychiatrists conducting a confirmatory search made a wrong diagnosis in 70% of the cases compared to 27% or 47% for a disconfirmatory or balanced information search (students: 63, 26 and 27%). Participants choosing the wrong diagnosis also prescribed different treatment options compared with participants choosing the correct diagnosis.
Confirmatory information search harbors the risk of wrong diagnostic decisions. Psychiatrists should be aware of confirmation bias and instructed in techniques to reduce bias.
Schizophrenia is a heterogeneous disorder in terms of patient response to antipsychotic treatment. Understanding the heterogeneity of treatment response may help to guide treatment decisions. This study was undertaken to capture inherent patterns of response to antipsychotic treatment in patients with schizophrenia, characterize the subgroups of patients with similar courses of response, and examine illness characteristics at baseline as possible predictors of response.
Growth mixture modeling (GMM) was applied to data from a randomized, double-blind, 12-week study of 628 patients with schizophrenia or schizo-affective disorder treated with risperidone or olanzapine.
Four distinct response trajectories based on Positive and Negative Syndrome Scale (PANSS) total score over 12 weeks were identified: Class 1 (420 patients, 80.6%) with moderate average baseline PANSS total score showing gradual symptom improvement; Class 2 (65 patients, 12.5%) showing rapid symptom improvement; Class 3 (24 patients, 4.6%) with high average baseline PANSS total score showing gradual symptom improvement; and Class 4 (12 patients, 2.3%) showing unsustained symptom improvement. Latent class membership of early responders (ER) and early non-responders (ENR) was determined based on 20% symptom improvement criteria at 2 weeks and ultimate responders (UR) and ultimate non-responders (UNR) based on 40% symptom improvement criteria at 12 weeks. Baseline factors with potential influence on latent class membership were identified.
This study identified four distinct treatment response patterns with predominant representation of responders or non-responders to treatment in these classes. This heterogeneity may represent discrete endophenotypes of response to treatment with different etiologic underpinnings.
The NASA Star and Exoplanet Database (NStED) is a general purpose stellar archive with the aim of providing support for NASA's planet finding and characterization goals, stellar astrophysics, and the planning of NASA and other space missions. There are two principal components of NStED: a database of (currently) 140,000 nearby stars and exoplanet-hosting stars, and an archive dedicated to high precision photometric surveys for transiting exoplanets. We present a summary of the NStED stellar database, functionality, tools, and user interface. NStED currently serves the following kinds of data for 140,000 stars (where available): coordinates, multiplicity, proper motion, parallax, spectral type, multiband photometry, radial velocity, metallicity, chromospheric and coronal activity index, and rotation velocity/period. Furthermore, the following derived quantities are given wherever possible: distance, effective temperature, mass, radius, luminosity, space motions, and physical/angular dimensions of habitable zone. Queries to NStED can be made using constraints on any combination of the above parameters. In addition, NStED provides tools to derive specific inferred quantities for the stars in the database, cross-referenced with available extra-solar planetary data for those host stars. NStED can be accessed at http://nsted.ipac.caltech.edu.
The NASA Star and Exoplanet Database (NStED) is a general purpose stellar archive with the aim of providing support for NASA's planet finding and characterization goals, stellar astrophysics, and the planning of NASA and other space missions. There are two principal components of NStED: a database of (currently) 140,000 nearby stars and exoplanet-hosting stars, and an archive dedicated to high-precision photometric surveys for transiting exoplanets. We present a summary of the latter component: the NStED Exoplanet Transit Survey Service (NStED-ETSS), along with its content, functionality, tools, and user interface. NStED-ETSS currently serves data from the TrES Survey of the Kepler Field as well as dedicated photometric surveys of four stellar clusters. NStED-ETSS aims to serve both the surveys and the broader astronomical community by archiving these data and making them available in a homogeneous format. Examples of usability of ETSS include investigation of any time-variable phenomena in data sets not studied by the original survey team, application of different techniques or algorithms for planet transit detections, combination of data from different surveys for given objects, statistical studies, etc. NStED-ETSS can be accessed at http://nsted.ipac.caltech.edu.
Blair equates the constructs of working memory (WM), executive function, and general fluid intelligence (gF). We argue that there is good reason not to equate these constructs. We view WM and gF as separable but highly related, and suggest that the mechanism behind the relationship is controlled attention – an ability that is dependent on normal functioning of the prefrontal cortex.
PLANET, the Probing Lensing Anomaly NETwork, is an international team
conducting observations of on-going gravitational microlensing
events from five sites in the southern hemisphere. Our primary goal is to
detect or to put constraints on sub-stellar companions of M dwarfs from the galactic disk.
We report the current status and discuss the future prospects.
A 2 m robotic telescope at Dome C which would benefit from continuous coverage and dream like seeing
(median of 0.27 arcsec) is currently the best option for a
ground based aggressive search for Earth-mass planets in the habitable zone.
Due to their extremely small luminosity compared to the stars they orbit, planets outside our own Solar System are extraordinarily difficult to detect directly in optical light. Careful photometric monitoring of distant stars, however, can reveal the presence of exoplanets via the microlensing or eclipsing effects they induce. The international PLANET collaboration is performing such monitoring using a cadre of semi-dedicated telescopes around the world. Their results constrain the number of gas giants orbiting 1–7 AU from the most typical stars in the Galaxy. Upgrades in the program are opening regions of “exoplanet discovery space” – toward smaller masses and larger orbital radii – that are inaccessible to the Doppler velocity technique.
The goal of our research is to combine porous silicon and enzymes in order to build hybrid platforms for extremely selective chemical sensing applications. For this, a new synthetic route to covalently anchor bio-molecules on photo-luminescent porous silicon (PL PSi) while preserving the optical properties of the matrix was developed. The hydride terminated porous silicon surface was covalently functionalized with t-butyloxycarbonyl protected amine by light-assisted hydrosysilation. Protein cross-linker chemistry was then used to extend the linker and immobilize various enzymes. The glu-coronidase enzyme/p-nitro-phenyl-beta-glucoronide substrate test system provided a proof of concept for an enzyme-based porous silicon detector. The enzymatic activity and the luminescence of the porous silicon platform were both retained after the functionali-zation procedure and, charge transfer between the products of the enzymatic breakdown and the silicon quantum dots was demonstrated. The organophosphorous hydrolase enzyme OPAA was then immobilized and tested on p-nitrophenyl-soman, a surrogate substrate for soman. The production of the hydrolysis product, p-nitrophenol, correlated with the reversible luminescence quenching of the porous silicon matrix demonstrating the relevance of the enzyme-based platform for detection applications. This detection scheme, although indirect, takes advantage of the extreme specificity of enzymes. The approach is general and can be implemented for a series of target molecules.
In this work, we report on the material properties of ZnO doped with Mn, Co, and Fe grown by a modified melt growth technique. X-ray diffraction measurements show that transition metals can be incorporated on Zn sites; an increase in the lattice parameter is apparent with increasing doping level. UV-visible transmission and reflectance measurements have also been performed. Absorption bands in the visible regime are distinctive to the individual transition metal dopants. A noticeable shift in the optical band edge has been observed from these Mn/Co/Fe-doped ZnO crystals in comparison with the undoped material. ZnO may also provide a suitable platform for the incorporation of transition metal elements through high temperature near equilibrium growth processes; however, further work is required in order to employ these materials for spintronic applications.
We review the current status and future prospects of the PLANET collaboration, an international team of astronomers performing high-precision photometric monitoring of microlensing events. Our photometric precision and sampling is characterised and the suitability of the database for variable star studies is discussed. Preliminary results on K-giant stability are presented.