Membrane lipidomics in schizophrenia patients: a correlational study with clinical and cognitive manifestations.

Schizophrenia is a severe mental condition in which several lipid abnormalities-either structural or metabolic-have been described. We tested the hypothesis that an abnormality in membrane lipid composition may contribute to aberrant dopamine signaling, and thereby symptoms and cognitive impairment, in schizophrenia (SCZ) patients. Antipsychotic-medicated and clinically stable SCZ outpatients (n=74) were compared with matched healthy subjects (HC, n=40). A lipidomic analysis was performed in red blood cell (RBC) membranes examining the major phospholipid (PL) classes and their associated fatty acids (FAs). Clinical manifestations were examined using the positive and negative syndrome scale (PANSS). Cognitive function was assessed using the Continuous Performance Test, Salience Attribution Test and Wisconsin Card Sorting Test. Sphingomyelin (SM) percentage was the lipid abnormality most robustly associated with a schizophrenia diagnosis. Two groups of patients were defined. The first group (SCZ c/SM-) is characterized by a low SM membrane content. In this group, all other PL classes, plasmalogen and key polyunsaturated FAs known to be involved in brain function, were significantly modified, identifying a very specific membrane lipid cluster. The second patient group (SCZ c/SM+) was similar to HCs in terms of RBC membrane SM composition. Compared with SCZ c/SM+, SCZ c/SM- patients were characterized by significantly more severe PANSS total, positive, disorganized/cognitive and excited psychopathology. Cognitive performance was also significantly poorer in this subgroup. These data show that a specific RBC membrane lipid cluster is associated with clinical and cognitive manifestations of dopamine dysfunction in schizophrenia patients. We speculate that this membrane lipid abnormality influences presynaptic dopamine signaling.

Nanomechanical properties of single amyloid fibrils.

Amyloid fibrils are traditionally associated with neurodegenerative diseases like Alzheimer's disease, Parkinson's disease or Creutzfeldt-Jakob disease. However, the ability to form amyloid fibrils appears to be a more generic property of proteins. While disease-related, or pathological, amyloid fibrils are relevant for understanding the pathology and course of the disease, functional amyloids are involved, for example, in the exceptionally strong adhesive properties of natural adhesives. Amyloid fibrils are thus becoming increasingly interesting as versatile nanobiomaterials for applications in biotechnology. In the last decade a number of studies have reported on the intriguing mechanical characteristics of amyloid fibrils. In most of these studies atomic force microscopy (AFM) and atomic force spectroscopy play a central role. AFM techniques make it possible to probe, at nanometer length scales, and with exquisite control over the applied forces, biological samples in different environmental conditions. In this review we describe the different AFM techniques used for probing mechanical properties of single amyloid fibrils on the nanoscale. An overview is given of the existing mechanical studies on amyloid. We discuss the difficulties encountered with respect to the small fibril sizes and polymorphic behavior of amyloid fibrils. In particular, the different conformational packing of monomers within the fibrils leads to a heterogeneity in mechanical properties. We conclude with a brief outlook on how our knowledge of these mechanical properties of the amyloid fibrils can be exploited in the construction of nanomaterials from amyloid fibrils.

Eurofit test battery in patients with schizophrenia or schizoaffective disorder: reliability and clinical correlates.

OBJECTIVE: To investigate the reproducibility of the Eurofit physical fitness test battery in patients with schizophrenia or schizoaffective disorder. Secondary aims were to assess clinical and demographic characteristics that correlate with the performance on the Eurofit and evaluation of the feasibility of the test. METHODS: Fifty patients with schizophrenia or schizoaffective disorder (mean age of 32.9±9.5 years) with a mean body mass index (BMI) of 26.1±6.0 kg/m(2) performed two Eurofit tests administered within 3 days. RESULTS: All Eurofit items showed good reproducibility with intraclass correlation coefficients ranging from 0.72 for flamingo balance to 0.98 for standing broad jump test. All participants could perform five of the seven test items without problems. The whole body balance and abdominal muscle endurance test could be executed by 74 and 90%, respectively. Significant correlations were found with age, BMI, waist circumference, dose of antipsychotic medication and extrapyramidal, negative and cognitive symptoms. CONCLUSIONS: The Eurofit test showed good reproducibility and can be recommended for evaluating physical fitness parameters in patients with schizophrenia or schizoaffective disorder. Physical fitness measures were related to both physical and mental health parameters.

Guidelines for screening and monitoring of cardiometabolic risk in schizophrenia: systematic evaluation.

BACKGROUND: Metabolic and cardiovascular health problems have become a major focus for clinical care and research in schizophrenia. AIMS: To evaluate the content and quality of screening guidelines for cardiovascular risk in schizophrenia. METHOD: Systematic review and quality assessment of guidelines/recommendations for cardiovascular risk in people with schizophrenia published between 2000 and 2010, using the Appraisal of Guidelines for Research and Evaluation (AGREE). RESULTS: The AGREE domain scores varied between the 18 identified guidelines. Most guidelines scored best on the domains 'scope and purpose' and 'clarity of presentation'. The domain 'rigour of development' was problematic in most guidelines, and the domains 'stakeholder involvement' and 'editorial independence' scored the lowest. The following measurements were recommended (in order of frequency): fasting glucose, body mass index, fasting triglycerides, fasting cholesterol, waist, high-density lipoprotein/low-density lipoprotein, blood pressure and symptoms of diabetes. In terms of interventions, most guidelines recommended advice on physical activity, diet, psychoeducation of the patient, treatment of lipid abnormalities, treatment of diabetes, referral for advice and treatment, psychoeducation of the family and smoking cessation advice. Compared across all domains and content, four European guidelines could be recommended. CONCLUSIONS: Four of the evaluated guidelines are of good quality and should guide clinicians' screening and monitoring practices. Future guideline development could be improved by increasing its rigour and assuring user and patient involvement.

Metaphor interpretation and use: a window into semantics in schizophrenia.

The nature of putative semantic anomalies in schizophrenia is controversial. Metaphor interpretation and use provide a useful methodology with which to probe semantics since metaphors are critical in reasoning processes and in how conceptual knowledge is organized. The first study examined free speech for figurative language. The second study explored whether emotional versus non-emotional metaphorical language interpretation elicits differences in the tendencies to produce idiosyncratic (bizarre) or literal interpretations or use of other metaphors to describe the meaning of a metaphor. The third study examined the interpretation of time metaphors. We expected the time perspective in ambiguous sentences to be differentially influenced by previously presented unambiguous sentences of a specific perspective, either events moving relative to a stationary observer (moving-time) or an observer moving relative to a stationary event (moving-ego). First, we found that patients used a similar amount of figurative language as control participants. Second, we did not find any difference between the groups in terms of idiosyncratic interpretations, although patients did interpret more metaphors literally and controls utilized more figurative language. Third, we did not find evidence of a difference between the groups in terms of time perspectives influencing ambiguous target sentences differentially. As operationalized here, the interpretation and use of metaphors is similar in patients with schizophrenia to that of healthy control participants. To the extent that metaphors recruit semantic processes this area of cognition is generally intact in schizophrenia.

Association of the metabolic syndrome with physical activity performance in patients with schizophrenia.

AIM: The primary aim of this study was to determine whether the presence of the metabolic syndrome (MetS) limits physical activity (PA) in patients with schizophrenia. A secondary aim was to investigate cross-sectional associations of leisure-time PA, sports participation and PA performance with MetS parameters. METHODS: Patients with schizophrenia who had MetS (n=37) were compared with those without MetS (n=69). Patients were assessed for PA performance using a 6-minute walk test (6MWT) and PA participation using the Baecke PA questionnaire, as well as for antipsychotic medication dose (expressed in chlorpromazine equivalents), negative symptoms and smoking behaviour. RESULTS: The two patient groups were similar in age, gender, mean antipsychotic medication dose, negative symptomatology and smoking behaviour. Distance achieved on the 6MWT was 13.7% shorter (P<0.001) in patients with versus patients without MetS (527.6±108.9 m vs 610.0±93.7 m, respectively). Patients with MetS were also significantly less involved in sports activities (P=0.001) and less physically active during leisure time (P=0.002). Also, the distance of the 6MWT was moderately correlated with body mass index (r=-0.44, P<0.001), waist circumference (r=-0.43, P<0.001), sports participation (r=0.60, P<0.001) and leisure-time PA (r=0.42, P<0.001). CONCLUSION: MetS is associated with poorer PA performance in patients with schizophrenia. The additional burden of MetS places patients with schizophrenia at even greater risk for physical and functional limitations in daily life.

Relationships between obesity, functional exercise capacity, physical activity participation and physical self-perception in people with schizophrenia.

OBJECTIVE: This study compared differences in functional exercise capacity between patients with schizophrenia and healthy controls. Physical self-perception and physical activity variables contributing to the variability in the distance achieved during a walk test were identified. METHOD: A total of 25 normal weight, 25 overweight and 10 obese patients and 40 healthy volunteers were included. Functional exercise capacity was explored with a 6-minute walk test. Level of physical activity was assessed using the Baecke questionnaire and physical self-perception using the physical self-perception profile. RESULTS: Obese patients walked a significantly shorter distance than overweight and normal weight patients (450.6 ± 97.7, 580.2 ± 116.0 and 615.8 ± 92.4 m resp., P < 0.001). All patients walked a shorter distance than healthy controls (710.6 ± 108.4 m, P < 0.001). Dyspnoea was only prevalent in schizophrenia (28.3%, P < 0.001) and especially in obese patients (90% vs. 40% in overweight and 27.3% in normal weight patients, P < 0.001). In multiple regression analysis, 59% of the variance in walking distance was explained by body mass index, perceived sports competence and condition, physical self-worth, level of sports participation and smoking behaviour. CONCLUSION: Functional exercise capacity in patients with schizophrenia is reduced not only by obesity, perceived discomfort and pain but also by a sedentary, unhealthy life style and a reduced physical self-perception.

Second-generation antipsychotics and constipation: a review of the literature.

Antipsychotics are the cornerstone in the management of psychotic disorders and schizophrenia. They are effective agents but also have a wide range of side effects. In the recent literature constipation as possible side effect has received little attention. A review of the literature concerning constipation associated with antipsychotics was performed. Overall constipation is a rarely studied or reported side effect of antipsychotic medication. Nevertheless constipation is a common side effect. Antipsychotic agents differ in their liability to induce constipation. Constipation can be severe and can lead to serious consequences such as paralytic ileus, bowel occlusion and death. Active screening, monitoring and treatment are recommended. Further research on incidence, prevalence, underlying mechanisms and preventive measures is required.