A Preliminary Report: The Hippocampus and Surrounding Temporal Cortex of Patients With Schizophrenia Have Impaired Blood-Brain Barrier

Schizophrenia (SZ) is one of the most severe forms of mental illness, yet mechanisms remain unclear. A widely established brain finding in SZ is hippocampal atrophy, and a coherent explanation similarly is lacking. Epidemiological evidence suggests increased cerebrovascular and cardiovascular complications in SZ independent of lifestyle and medication, pointing to disease-specific pathology. Endothelial cell contributions to blood-brain barrier (BBB) compromise may influence neurovascular unit and peripheral vascular function, and we hypothesize that downstream functional and structural abnormalities may be explained by impaired BBB

Distress intolerance and clinical functioning in persons with schizophrenia

Impaired tolerance to distress may help explain part of the cognitive and functional impairments in schizophrenia. This project investigated distress intolerance in schizophrenia patients (SZ) as compared to controls, and whether distress intolerance represented an independent domain in relationship to symptoms, cognition, and functional capacity. Healthy controls (n=43) and SZ (n=65) completed a psychological distress challenge experiment and their levels of intolerance to distress were estimated. SZ showed increased distress intolerance such that they were significantly more likely to terminate the distress challenge session early compared to controls. Greater distress intolerance was associated with reduced functional capacity and worse cognitive performance in SZ. Mediation analyses suggested that distress intolerance had an independent effect on functional capacity, while some of this effect was mediated by cognitive performance. Our results suggest that distress intolerance is a promising domain for treatment research, and functional capacity may be improved by targeting treatments towards SZ patient’s ability to tolerate distress

Sedimentology of Acid Saline Lakes in Southern Western Australia: Newly Described Processes and Products of an Extreme Environment

Naturally acid saline systems with pH values between 1.7 and 4 are common on the Yilgarn Craton of southern Western Australia. a combination of physical and chemical processes here yield a previously undescribed type of modern sedimentary environment. Flooding, evapoconcentration, desiccation, and eolian transport at the surface, as well as influx of acid saline groundwaters, strongly influence these lakes. Halite, gypsum, kaolinite, and iron oxides precipitate from acid hypersaline lake waters. Shallow acid saline groundwaters affect the sediments of the lakes and associated mudflats, sandflats, channels, and dunes by precipitating early diagenetic halite, gypsum, iron oxides, clays, jarosite, and alunite. These modern environments would likely yield a rock record composed mostly of bedded red siliciclastic and reworked gypsum sand, alternating with less common beds of bottom-growth gypsum and halite, with alteration by early diagenetic features diagnostic of acid saline waters. This documentation of sedimentary processes and products of modern acid saline environments is an addition to the comparative sedimentology knowledge base and an expansion of the traditional models for classifying brines. Implications include better interpretations of terrestrial redbeds and lithified martian strata, improved acid remediation methods, new models for the formation and occlusion of pores, and the new setting for finding previously undescribed extremophiles

Multi-visceral resection of pancreatic VIPoma in a patient with sinistral portal hypertension

BACKGROUND: VIPomas are rare neuroendocrine tumors poorly described in the literature. Aggressive resection of patients with advanced VIPoma neuroendocrine tumors has rarely been reported. CASE PRESENTATION: A 46 year old women presented with abdominal pain and diarrhea. A three-dimensional (3-D) pancreas protocol computed tomography scan revealed an 18 × 12 cm pancreatic VIPoma abutting the liver, stomach, spleen, left adrenal, colon that also invaded the distal duodenum – proximal jejunum at the ligament of Treitz in association with sinistral portal hypertension. Following preoperative proximal splenic artery embolization, the patient with underwent successful en bloc resection of the locally advanced VIPoma in conjunction with a diaphragmatic resection, total gastrectomy, splenectomy, left adrenalectomy, as well as small and large bowel resection. The estimated blood loss was 500 ml. All margins were negative (R0 resection). The patient is alive and disease-free. CONCLUSION: This case illustrates the role of aggressive resection of pancreatic neuroendocrine tumors and highlights several key technical points that allowed for successful resection

Genetic analysis of cortical thickness and fractional anisotropy of water diffusion in the brain

Objectives: The thickness of the brain’s cortical gray matter (GM) and the fractional anisotropy (FA) of the cerebral white matter (WM) each follow an inverted U-shape trajectory with age. The two measures are positively correlated and may be modulated by common biological mechanisms. We employed four types of genetic analyses to localize individual genes acting pleiotropically upon these phenotypes. Methods: Whole-brain and regional GM thickness and FA values were measured from high-resolution anatomical and diffusion tensor MR images collected from 712, Mexican American participants (438 females, age = 47.9 ± 13.2 years) recruited from 73 (9.7 ± 9.3 individuals/family) large families. The significance of the correlation between two traits was estimated using a bivariate genetic correlation analysis. Localization of chromosomal regions that jointly influenced both traits was performed using whole-genome quantitative trait loci (QTL) analysis. Gene localization was performed using SNP genotyping on Illumina 1M chip and correlation with leukocyte-based gene-expression analyses. The gene-expressions were measured using the Illumina BeadChip. These data were available for 371 subjects. Results: Significant genetic correlation was observed among GM thickness and FA values. Significant logarithm of odds (LOD ≥ 3.0) QTLs were localized within chromosome 15q22–23. More detailed localization reported no significant association (p \u3c 5·10−5) for 1565 SNPs located within the QTLs. Post hoc analysis indicated that 40% of the potentially significant (p ≤ 10−3) SNPs were localized to the related orphan receptor alpha (RORA) and NARG2 genes. A potentially significant association was observed for the rs2456930 polymorphism reported as a significant GWAS finding in Alzheimer’s disease neuroimaging initiative subjects. The expression levels for RORA and ADAM10 genes were significantly (p \u3c 0.05) correlated with both FA and GM thickness. NARG2 expressions were significantly correlated with GM thickness (p \u3c 0.05) but failed to show a significant correlation (p = 0.09) with FA. Discussion: This study identified a novel, significant QTL at 15q22–23. SNP correlation with gene-expression analyses indicated that RORA, NARG2, and ADAM10 jointly influence GM thickness and WM–FA values

Lack of association between COMT gene and deficit/nondeficit schizophrenia

BACKGROUND: The dopamine dysregulation hypothesis of schizophrenia posits that positive, negative and cognitive symptoms correlate with cortical/subcortical imbalances in dopaminergic transmission. A functional polymorphism (Val(158)Met) in the catechol-O-methyltransferase (COMT) gene is implicated in the pathophysiology of schizophrenia by its effect on prefrontal dopamine transmission, and its unique impact on prefrontal cognitive and behavioral phenotypes. Cognitive impairments and negative symptoms in schizophrenia have been hypothesized to be associated with hypodopaminergic states. Schizophrenia patients with the deficit syndrome are characterized by primary enduring negative symptoms, impairment on neurocognitive tasks sensitive to frontal and parietal cortical functioning, and poorer functional outcome compared to non-deficit patients. METHODS: Eighty-six schizophrenia cases that met DSM-IV criteria for schizophrenia were recruited. Additional categorization into deficit and nondeficit syndrome was performed using the Schedule for the Deficit Syndrome (SDS). A healthy comparison group (n = 50) matched to cases on age and ethnicity was recruited. Allele and genotype frequencies of the Val(158)Met polymorphism were compared among healthy controls, and schizophrenia cases with the deficit (n = 21), and nondeficit syndrome (n = 65). RESULTS: There was a significant difference in Val/Val genotype frequencies between schizophrenia cases (combined deficit/nondeficit) and healthy controls (p = 0.004). No significant differences in allele or genotype frequencies were observed between deficit and nondeficit cases. CONCLUSION: Results from this preliminary analysis failed to show an effect of COMT gene on deficit schizophrenia

Cortisol Reactivity to Stress and Its Association With White Matter Integrity in Adults With Schizophrenia

While acute hypothalamic-pituitary-adrenal axis response to stress is often adaptive, prolonged responses may have detrimental effects. Many components of white matter structures are sensitive to prolonged cortisol exposure. We aimed to identify a behavioral laboratory assay for which cortisol response related to brain pathophysiology in schizophrenia. We hypothesized that an abnormally prolonged cortisol response to stress may be linked to abnormal white matter integrity in patients with schizophrenia

Multi-site genetic analysis of diffusion images and voxelwise heritability analysis : a pilot project of the ENIGMA–DTI working group

The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium was set up to analyze brain measures and genotypes from multiple sites across the world to improve the power to detect genetic variants that influence the brain. Diffusion tensor imaging (DTI) yields quantitative measures sensitive to brain development and degeneration, and some common genetic variants may be associated with white matter integrity or connectivity. DTI measures, such as the fractional anisotropy (FA) of water diffusion, may be useful for identifying genetic variants that influence brain microstructure. However, genome-wide association studies (GWAS) require large populations to obtain sufficient power to detect and replicate significant effects, motivating a multi-site consortium effort. As part of an ENIGMA–DTI working group, we analyzed high-resolution FA images from multiple imaging sites across North America, Australia, and Europe, to address the challenge of harmonizing imaging data collected at multiple sites. Four hundred images of healthy adults aged 18–85 from four sites were used to create a template and corresponding skeletonized FA image as a common reference space. Using twin and pedigree samples of different ethnicities, we used our common template to evaluate the heritability of tract-derived FA measures. We show that our template is reliable for integrating multiple datasets by combining results through meta-analysis and unifying the data through exploratory mega-analyses. Our results may help prioritize regions of the FA map that are consistently influenced by additive genetic factors for future genetic discovery studies. Protocols and templates are publicly available at (http://enigma.loni.ucla.edu/ongoing/dti-working-group/)

Interatomic potentials for atomistic simulations of the Ti-Al system

Semi-empirical interatomic potentials have been developed for Al, alpha-Ti, and gamma-TiAl within the embedded atomic method (EAM) by fitting to a large database of experimental as well as ab-initio data. The ab-initio calculations were performed by the linear augmented plane wave (LAPW) method within the density functional theory to obtain the equations of state for a number of crystal structures of the Ti-Al system. Some of the calculated LAPW energies were used for fitting the potentials while others for examining their quality. The potentials correctly predict the equilibrium crystal structures of the phases and accurately reproduce their basic lattice properties. The potentials are applied to calculate the energies of point defects, surfaces, planar faults in the equilibrium structures. Unlike earlier EAM potentials for the Ti-Al system, the proposed potentials provide reasonable description of the lattice thermal expansion, demonstrating their usefulness in the molecular dynamics or Monte Carlo studies at high temperatures. The energy along the tetragonal deformation path (Bain transformation) in gamma-TiAl calculated with the EAM potential is in a fairly good agreement with LAPW calculations. Equilibrium point defect concentrations in gamma-TiAl are studied using the EAM potential. It is found that antisite defects strongly dominate over vacancies at all compositions around stoichiometry, indicating that gamm-TiAl is an antisite disorder compound in agreement with experimental data.Comment: 46 pages, 6 figures (Physical Review B, in press

Spin injection and spin accumulation in all-metal mesoscopic spin valves

We study the electrical injection and detection of spin accumulation in lateral ferromagnetic metal-nonmagnetic metal-ferromagnetic metal (F/N/F) spin valve devices with transparent interfaces. Different ferromagnetic metals, permalloy (Py), cobalt (Co) and nickel (Ni), are used as electrical spin injectors and detectors. For the nonmagnetic metal both aluminium (Al) and copper (Cu) are used. Our multi-terminal geometry allows us to experimentally separate the spin valve effect from other magneto resistance signals such as the anomalous magneto resistance (AMR) and Hall effects. We find that the AMR contribution of the ferromagnetic contacts can dominate the amplitude of the spin valve effect, making it impossible to observe the spin valve effect in a 'conventional' measurement geometry. In a 'non local' spin valve measurement we are able to completely isolate the spin valve signal and observe clear spin accumulation signals at T=4.2 K as well as at room temperature (RT). For aluminum we obtain spin relaxation lengths (lambda_{sf}) of 1.2 mu m and 600 nm at T=4.2 K and RT respectively, whereas for copper we obtain 1.0 mu m and 350 nm. The spin relaxation times tau_{sf} in Al and Cu are compared with theory and results obtained from giant magneto resistance (GMR), conduction electron spin resonance (CESR), anti-weak localization and superconducting tunneling experiments. The spin valve signals generated by the Py electrodes (alpha_F lambda_F=0.5 [1.2] nm at RT [T=4.2 K]) are larger than the Co electrodes (alpha_F lambda_F=0.3 [0.7] nm at RT [T=4.2 K]), whereas for Ni (alpha_F lambda_F<0.3 nm at RT and T=4.2 K) no spin signal is observed. These values are compared to the results obtained from GMR experiments.Comment: 16 pages, 12 figures, submitted to PR