Microvascular changes in late-life schizophrenia and mood disorders: stereological assessment of capillary diameters in anterior cingulate cortex.

AIMS: Previous neuroimaging reports described morphological and functional abnormalities in anterior cingulate cortex (ACC) in schizophrenia and mood disorders. In earlier neuropathological studies, microvascular changes that could affect brain perfusion in these disorders have rarely been studied. Here, we analysed morphological parameters of capillaries in this area in elderly cases affected by these psychiatric disorders. METHODS: We analysed microvessel diameters in the dorsal and subgenual parts of the ACC in eight patients with schizophrenia, 10 patients with sporadic bipolar disorder, eight patients with sporadic major depression, and seven age- and gender-matched control cases on sections stained with modified Gallyas silver impregnation using a stereological counting approach. All individuals were drug-naïve or had received psychotropic medication for less than 6 months, and had no history of substance abuse. Statistical analysis included Kruskal-Wallis group comparisons with Bonferroni correction as well as multivariate regression models. RESULTS: Mean capillary diameter was significantly decreased in the dorsal and subgenual parts of areas 24 in bipolar and unipolar depression cases, both in layers III and V, whereas schizophrenia patients were comparable with controls. These differences persisted when controlling for age, local neuronal densities, and cortical thickness. In addition, cortical thickness was significantly smaller in both layers in schizophrenia patients. CONCLUSIONS: Our findings indicate that capillary diameters in bipolar and unipolar depression but not in schizophrenia are reduced in ACC. The significance of these findings is discussed in the light of the cytoarchitecture, brain metabolism and perfusion changes observed in ACC in mood disorders.

A randomized trial of spiritual assessment of outpatients with schizophrenia: Patients' and clinicians' experience

Objective: Recovery-oriented care for patients with schizophrenia involves consideration of cultural issues, such as religion and spirituality. However, there is evidence that psychiatrists rarely address such topics. This study examined acceptance of a spiritual assessment by patients and clinicians, suggestions for treatment that arose from the assessment, and patient outcomes-in terms of treatment compliance and satisfaction with care (as measured by treatment alliance). Methods: Outpatients with psychosis were randomly assigned to two groups: an intervention group that received traditional treatment and a religious and spiritual assessment (N=40) and a control group that received only traditional treatment (N=38). Eight psychiatrists were trained to administer the assessment to their established and stable patients. After each administration, the psychiatrist attended a supervision session with a psychiatrist and a psychologist of religion. Baseline and three-month data were collected. Results: The spiritual assessment was well accepted by patients. During supervision, psychiatrists reported potential clinical uses for the assessment information for 67% of patients. No between-group differences in medication adherence and satisfaction with care were found at three months, although patients in the in- tervention group had significantly better appointment attendance dur- ing the follow-up period. Their interest in discussing religion and spirituality with their psychiatrists remained high. The process was not as well accepted by psychiatrists. Conclusions: Spiritual assessment can raise important clinical issues in the treatment of patients with chronic schizophrenia. Cultural factors, such as religion and spirituality, should be considered early in clinical training, because many clinicians are not at ease addressing such topics with patients.

The effect of cognitive behavioral treatment on the positive symptoms of schizophrenia spectrum disorders: a meta-analysis

(from the journal abstract) Background: Despite the effectiveness of anti-psychotic pharmacotherapy, residual hallucinations and delusions do not completely resolve in some medicated patients. Additional cognitive behavioral therapy (CBT) seems to improve the management of positive symptoms. Despite promising results, the efficacy of CBT is still unclear. The present study addresses this issue taking into account a number of newly published controlled studies. Method: Fourteen studies including 1484 patients, published between 1990 and 2004 were identified and a meta-analysis of their results performed. Results: Compared to other adjunctive measures, CBT showed significant reduction in positive symptoms and there was a higher benefit of CBT for patients suffering an acute psychotic episode versus the chronic condition (effect size of 0.57 vs. 0.27). Discussion: CBT is a promising adjunctive treatment for positive symptoms in schizophrenia spectrum disorders. However, a number of potentially modifying variables have not yet been examined, such as therapeutic alliance and neuropsychological deficits. (PsycINFO Database Record (c) 2005 APA, all rights reserved)

Visuo-spatial processing in a dynamic and a static working memory paradigm in schizophrenia.

Recent findings suggest that the visuo-spatial sketchpad (VSSP) may be divided into two sub-components processing dynamic or static visual information. This model may be useful to elucidate the confusion of data concerning the functioning of the VSSP in schizophrenia. The present study examined patients with schizophrenia and matched controls in a new working memory paradigm involving dynamic (the Ball Flight Task - BFT) or static (the Static Pattern Task - SPT) visual stimuli. In the BFT, the responses of the patients were apparently based on the retention of the last set of segments of the perceived trajectory, whereas control subjects relied on a more global strategy. We assume that the patients' performances are the result of a reduced capacity in chunking visual information since they relied mainly on the retention of the last set of segments. This assumption is confirmed by the poor performance of the patients in the static task (SPT), which requires a combination of stimulus components into object representations. We assume that the static/dynamic distinction may help us to understand the VSSP deficits in schizophrenia. This distinction also raises questions about the hypothesis that visuo-spatial working memory can simply be dissociated into visual and spatial sub-components.

Molecular epidemiology of methicillin-resistant Staphylococcus aureus in Switzerland: sampling only invasive isolates does not allow a representative description of the local diversity of clones.

We conducted a molecular study of MRSA isolated in Swiss hospitals, including the first five consecutive isolates recovered from blood cultures and the first ten isolates recovered from other sites in newly identified carriers. Among 73 MRSA isolates, 44 different double locus sequence typing (DLST) types and 32 spa types were observed. Most isolates belonged to the NewYork/Japan, the UK-EMRSA-15, the South German and the Berlin clones. In a country with a low to moderate MRSA incidence, inclusion of non-invasive isolates allowed a more accurate description of the diversity.

Glutathione precursor N-acetyl-cysteine modulates EEG synchronization in schizophrenia patients: a double-blind, randomized, placebo-controlled trial.

Glutathione (GSH) dysregulation at the gene, protein, and functional levels has been observed in schizophrenia patients. Together with disease-like anomalies in GSH deficit experimental models, it suggests that such redox dysregulation can play a critical role in altering neural connectivity and synchronization, and thus possibly causing schizophrenia symptoms. To determine whether increased GSH levels would modulate EEG synchronization, N-acetyl-cysteine (NAC), a glutathione precursor, was administered to patients in a randomized, double-blind, crossover protocol for 60 days, followed by placebo for another 60 days (or vice versa). We analyzed whole-head topography of the multivariate phase synchronization (MPS) for 128-channel resting-state EEGs that were recorded at the onset, at the point of crossover, and at the end of the protocol. In this proof of concept study, the treatment with NAC significantly increased MPS compared to placebo over the left parieto-temporal, the right temporal, and the bilateral prefrontal regions. These changes were robust both at the group and at the individual level. Although MPS increase was observed in the absence of clinical improvement at a group level, it correlated with individual change estimated by Liddle's disorganization scale. Therefore, significant changes in EEG synchronization induced by NAC administration may precede clinically detectable improvement, highlighting its possible utility as a biomarker of treatment efficacy. TRIAL REGISTRATION: ClinicalTrials.gov NCT01506765.

Epidemiologie und Prävention des Hautmelanoms in der Schweiz: Update 2010. [Epidemiology and prevention of melanoma in Switzerland: 2010 update]

Zusammenfassung] Die Inzidenz des malignen Melanoms steigt seit über 50 Jahren bei der weißen Bevölkerung stark an. Die Schweiz ist mit ungefähr 1900 neu diagnostizierten Fällen pro Jahr das am stärksten betroffene Land Europas (16/100 000 Welt-standardisierte Rate). In letzter Zeit sind regionale Unterschiede mit höherer Inzidenz in den Westschweizer Kantonen festzustellen. Änderungen in Wissen und Verhalten der Schweizer Bevölkerung gegenüber dem Schutz vor Sonnenexposition bestehen noch zu wenig lange und sind zu bescheiden, als dass sie schon einen Einfluss auf die Inzidenz hätten haben können. Dank der seit 20 Jahren betriebenen Früherfassung sind Überlebensrate und Anteil an dünnen Melanomen gestiegen, allerdings bei gleichbleibender Inzidenz dicker Läsionen. Die Mortalität aufgrund des malignen Melanoms ist neuerdings rückläufig, vor allem bei den Frauen. Werden die gegenwärtigen Präventionsbemühungen weitergeführt, dürften sich bald noch mehr Erfolge zeigen. [Abstract] The incidence of cutaneous malignant melanoma has steadily increased in Caucasian populations over the last decades. With around 1900 new cases each year, Switzerland has one of the highest melanoma rates in Europe (16/100 000 world-standardised rate). Regional differences are emerging within Switzerland, with a higher incidence in the western (French-speaking) region. Observed changes in sun protection attitudes and knowledge in the Swiss population have yet no impact on the incidence trend. Early detection, carried out since the mid 1980s in Switzerland, has led to a substantial increase in survival and rates of thin melanoma, without material change in rates of thick melanoma. Mortality from melanoma has recently decreased, earlier in women than men. The efficacy of prevention campaigns should soon become more blatant if current efforts persist.

Is trauma in Switzerland any different? epidemiology and patterns of injury in major trauma - a 5-year review from a Swiss trauma centre.

Switzerland, the country with the highest health expenditure per capita, is lacking data on trauma care and system planning. Recently, 12 trauma centres were designated to be reassessed through a future national trauma registry by 2015. Lausanne University Hospital launched the first Swiss trauma registry in 2008, which contains the largest database on trauma activity nationwide. METHODS: Prospective analysis of data from consecutively admitted shock room patients from 1 January 2008 to 31 December 2012. Shock room admission is based on physiology and mechanism of injury, assessed by prehospital physicians. Management follows a surgeon-led multidisciplinary approach. Injuries are coded by Association for the Advancement of Automotive Medicine (AAAM) certified coders. RESULTS: Over the 5 years, 1,599 trauma patients were admitted, predominantly males with a median age of 41.4 years and median injury severity score (ISS) of 13. Rate of ISS >15 was 42%. Principal mechanisms of injury were road traffic (40.4%) and falls (34.4%), with 91.5% blunt trauma. Principal patterns were brain (64.4%), chest (59.8%) and extremity/pelvic girdle (52.9%) injuries. Severe (abbreviated injury scale [AIS] score ≥ 3) orthopaedic injuries, defined as extremity and spine injuries together, accounted for 67.1%. Overall, 29.1% underwent immediate intervention, mainly by orthopaedics (27.3%), neurosurgeons (26.3 %) and visceral surgeons (13.9%); 43.8% underwent a surgical intervention within the first 24 hours and 59.1% during their hospitalisation. In-hospital mortality for patients with ISS >15 was 26.2%. CONCLUSION: This is the first 5-year report on trauma in Switzerland. Trauma workload was similar to other European countries. Despite high levels of healthcare, mortality exceeds published rates by >50%. Regardless of the importance of a multidisciplinary approach, trauma remains a surgical disease and needs dedicated surgical resources.

Genetic vulnerability factor for schizophrenia: association with glutamate cysteine ligase modifier gene and abnormal enzyme activity

Background: We previously reported in schizophrenia patients a decreased level of glutathione ([GSH]), the principal non-protein antioxidant and redox regulator, both in cerebrospinal-fluid and prefrontal cortex. To identify possible genetic causation, we studied genes involved in GSH metabolism. Methods: Genotyping: mass spectrometry analysis of polymerase chain reaction (PCR) amplified DNA fragments purified from peripheral blood. Gene expression: real-time PCR of total RNA isolated from fibroblast cultures derived from skin of patients (DSM-IV) and healthy controls (DIGS). Results: Case-control association study of single nucleotide polymorphisms (SNP) from the GSH key synthesizing enzyme glutamate-cysteine-ligase (GCL) modifier subunit (GCLM) was performed in two populations: Swiss (patients/controls: 40/31) and Danish (349/348). We found a strong association of SNP rs2301022 in GCLM gene (Danish: c2=3.2; P=0.001 after correction for multiple testing). Evidence for GCLM as a risk factor was confirmed in linkage study of NIMH families. Moreover, we observed a decrease in GCLM mRNA levels in patient fibroblasts, consistently with the association study. Interestingly, Dalton and collaborators reported in GCLM knock-out mice an increased feedback inhibition of GCL activity, resulting in 60% decrease of brain [GSH], a situation analogous to patients. These mice also exhibited an increased sensitivity to oxidative stress. Similarly, under oxidative stress conditions, GCL enzymatic activity was also decreased in patient fibroblasts. Conclusions: These results at the genetic and functional levels, combined with observations that GSH deficient models reveal morphological, electrophysiological, and behavioral anomalies analogous to those observed in patients, suggest that GCLM allelic variant is a vulnerability factor for schizophrenia.