Cognitive and functional deficits are associated with white matter abnormalities in two independent cohorts of patients with schizophrenia

European Archives of Psychiatry and Clinical Neuroscience - Significant evidence links white matter (WM) microstructural abnormalities to cognitive impairment in schizophrenia (SZ), but the...     

The effects of physical exercise in schizophrenia and affective disorders

Affective and non-affective psychoses are severe and frequent psychiatric disorders. Amongst others, they not only have a profound impact on affected individuals through their symptomatology, but also regarding cognition, brain structure and function. Cognitive impairment influences patients’ quality of life as well as their ability to work and being employed. While exercise therapy has been implemented in the treatment of psychiatric conditions since the days of Kraepelin and Bleuler, the underlying mechanisms have never been systematically studied. Since the early 1990s, studies emerged examining the effect of physical exercise in animal models, revealing stimulation of neurogenesis, synaptogenesis and neurotransmission. Based on that body of work, clinical studies have been carried out in both healthy humans and in patient populations. These studies differ with regard to homogenous study samples, sample size, type and duration of exercise, outcome variables and measurement techniques. Based on their review, we draw conclusions regarding recommendations for future research strategies showing that modern therapeutic approaches should include physical exercise as part of a multimodal intervention programme to improve psychopathology and cognitive symptoms in schizophrenia and affective disorders.     

Inhibition of endothelial cell Ca2+ entry and transient receptor potential channels by Sigma-1 receptor ligands

Background and Purpose

The Sigma-1 receptor (Sig1R) impacts on calcium ion signalling and has a plethora of ligands. This study investigated Sig1R and its ligands in relation to endogenous calcium events of endothelial cells and transient receptor potential (TRP) channels.

Experimental Approach

Intracellular calcium and patch clamp measurements were made from human saphenous vein endothelial cells and HEK 293 cells expressing exogenous human TRPC5, TRPM2 or TRPM3. Sig1R ligands were applied and short interfering RNA was used to deplete Sig1R. TRP channels tagged with fluorescent proteins were used for subcellular localization studies.

Key Results

In endothelial cells, 10–100 μM of the Sig1R antagonist BD1063 inhibited sustained but not transient calcium responses evoked by histamine. The Sig1R agonist 4-IBP and related antagonist BD1047 were also inhibitory. The Sig1R agonist {"type":"entrez-protein","attrs":{"text":"SKF10047","term_id":"1156210965","term_text":"SKF10047"}}SKF10047 had no effect. Sustained calcium entry evoked by VEGF or hydrogen peroxide was also inhibited by BD1063, BD1047 or 4-IBP, but not {"type":"entrez-protein","attrs":{"text":"SKF10047","term_id":"1156210965","term_text":"SKF10047"}}SKF10047. 4-IBP, BD1047 and BD1063 inhibited TRPC5 or TRPM3, but not TRPM2. Inhibitory effects of BD1047 were rapid in onset and readily reversed on washout. {"type":"entrez-protein","attrs":{"text":"SKF10047","term_id":"1156210965","term_text":"SKF10047"}}SKF10047 inhibited TRPC5 but not TRPM3 or TRPM2. Depletion of Sig1R did not prevent the inhibitory actions of BD1063 or BD1047 and Sig1R did not co-localize with TRPC5 or TRPM3.

Conclusions and Implications

The data suggest that two types of Sig1R ligand (BD1047/BD1063 and 4-IBP) are inhibitors of receptor- or chemically activated calcium entry channels, acting relatively directly and independently of the Sig1R. Chemical foundations for TRP channel inhibitors are suggested.     

Effects of Endurance Training Combined With Cognitive Remediation on Everyday Functioning,Symptoms, and Cognition in Multiepisode Schizophrenia Patients

Aerobic exercise has been shown to improve symptoms in multiepisode schizophrenia, including cognitive impairments, but results are inconsistent. Therefore, we evaluated the effects of an enriched environment paradigm consisting of bicycle ergometer training and add-on computer-assisted cognitive remediation (CACR) training. To our knowledge, this is the first study to evaluate such an enriched environment paradigm in multiepisode schizophrenia. Twenty-two multiepisode schizophrenia patients and 22 age- and gender-matched healthy controls underwent 3 months of endurance training (30min, 3 times/wk); CACR training (30min, 2 times/wk) was added from week 6. Twenty-one additionally recruited schizophrenia patients played table soccer (known as “foosball” in the United States) over the same period and also received the same CACR training. At baseline and after 6 weeks and 3 months, we measured the Global Assessment of Functioning (GAF), Social Adjustment Scale-II (SAS-II), schizophrenia symptoms (Positive and Negative Syndrome Scale), and cognitive domains (Verbal Learning Memory Test [VLMT], Wisconsin Card Sorting Test [WCST], and Trail Making Test). After 3 months, we observed a significant improvement in GAF and in SAS-II social/leisure activities and household functioning adaptation in the endurance training augmented with cognitive remediation, but not in the table soccer augmented with cognitive remediation group. The severity of negative symptoms and performance in the VLMT and WCST improved significantly in the schizophrenia endurance training augmented with cognitive remediation group from week 6 to the end of the 3-month training period. Future studies should investigate longer intervention periods to show whether endurance training induces stable improvements in everyday functioning.Key words: aerobic exercise, endurance training, cognitive remediation, schizophrenia, everyday functioning     

Antineutrophil cytoplasmic antibody measurement: advantages and disadvantages of a capture PR3 ELISA and a direct PR3 ELISA

AIM: To compare the performance of a capture proteinase 3 enzyme linked immunosorbent assay (PR3 ELISA) with a direct PR3 ELISA in the measurement of PR3 antineutrophil cytoplasmic antibodies (ANCA). METHOD: The performance of both assays systems was compared using two sets of sera. Sera from patients (n = 49) suffering from Wegener's granulomatosis (WG) and fulfilling the American College of Rheumatology classification criteria (or a modification of those criteria that allowed for ANCA positivity) were used along with sera from a group of patients (n = 48) considered to have a clinically false positive PR3 ANCA result when measured by routine direct ELISA. RESULTS: Using the assay specific cut-offs, the direct ELISA gave a positive result in 92% on repeat testing and the capture ELISA a positive result in 84% of sera from patients with WG. The capture ELISA was negative in 75% of patients considered to have a false positive PR3 ANCA on initial testing by direct ELISA (27% were negative on repeat testing by direct ELISA). The mean concentration of PR3 ANCA in WG patient sera measured by the capture ELISA was significantly higher than that measured by the direct ELISA. The capture PR3 ELISA had a broader analytical range which was also reflected in PR3 ANCA concentrations measured in serial serum samples from WG patients. CONCLUSION: In this study the direct PR3 ELISA performed better as a screening test for PR3 ANCA compared with the capture PR3 ELISA, mainly because the cut-off for the capture ELISA needed to be set higher to avoid non-specific binding. In contrast, the improved analytical range of the capture ELISA made it a potentially more useful method for monitoring serial PR3 ANCA concentrations. In specific serum samples the capture ELISA was better able to discriminate 'false positive' PR3 ANCA.     

Evaluation of 1,1,1-trichloroethane and flurothyl locomotor effects following diazepam treatment in mice.

The abused volatile solvent 1,1,1-trichloroethane (TCE) shares many acute behavioral effects with central nervous system (CNS) depressants; however, demonstration of tolerance to these effects has been difficult. The purpose of the present study was to investigate the development of TCE-induced changes in locomotor activity in mice following repeated injections with diazepam. In the initial concentration-effect curve determinations, diazepam decreased locomotor activity at all doses tested and TCE produced a biphasic effect, increasing locomotor activity at lower concentrations with return to control levels at a high (16,000 ppm) concentration. Flurothyl, a vapor with convulsive properties, had no pronounced effects on locomotor activity at subconvulsant concentrations. Following four daily injections with vehicle or with 10 mg/kg/day diazepam, mice were administered the same concentration of drug/inhalant that they received initially and were retested for locomotor activity effects. Concentration-effect curves for diazepam and flurothyl were not altered by this modest regimen of repeated dosing with diazepam. In contrast, sensitization to the locomotor-stimulating effects of TCE was observed in diazepam-treated mice, but not in vehicle-treated mice. These results suggest that the development of sensitization to TCE involves common mechanisms with those that are affected by repeated dosing with the CNS depressant diazepam.