Anhedonia in schizophrenia: distinctions between anticipatory and consummatory pleasure

Research on anhedonia in schizophrenia has revealed mixed results, with patients reporting greater anhedonia than healthy controls on self-report measures and semi-structured interviews, but also reporting comparable experiences of positive emotions in response to pleasurable stimuli. Basic science points to the importance of distinguishing between anticipatory and consummatory (or in-the-moment) pleasure experiences, and this distinction may help to reconcile the mixed findings on anhedonia in schizophrenia. In two studies, we tested the hypothesis that anhedonia in schizophrenia reflects a deficit in anticipatory pleasure but not consummatory pleasure. In Study 1, we used experience sampling methodology to assess reported experiences of consummatory and anticipated pleasure among schizophrenia patients and controls. In Study 2, schizophrenia patients and controls completed a self-report trait measure of anticipatory and consummatory pleasure and interviews that assessed negative symptoms, including anhedonia, and community functioning. In both studies, we found evidence for an anticipatory but not a consummatory pleasure deficit in schizophrenia. In addition, anticipatory pleasure was related to clinical ratings of anhedonia and functional outcome. Clinical and research implications of these findings are discussed.     

Mobility limitations in persons with psychotic disorder: findings from a population-based survey

BACKGROUND: There are few reports on mobility limitations in persons with psychotic disorder although restrictions in mobility may aggravate the general functional limitations of these patients. Our aim was to investigate mobility limitations among subjects with psychotic disorder in a general population-based sample. METHODS: A nationally representative sample of 6,927 persons aged 30 and older self-reported mobility limitations in an interview and was examined in performance tests. Diagnostic assessment of DSM-IV psychotic disorders combined SCID interview and case note data. Lifetime-ever diagnoses of psychotic disorder were classified into schizophrenia, other nonaffective psychotic disorders and affective psychoses. RESULTS: Self-reported mobility limitations were highly prevalent in persons with schizophrenia and other nonaffective psychosis, but not in the affective psychosis group. After adjusting for age and sex, persons with schizophrenia and other nonaffective psychoses but not affective psychoses had significantly increased odds of having both self-reported and test-based mobility limitations as well as weak muscle strength. Schizophrenia remained an independent predictor of mobility limitations even after controlling for lifestyle-related factors and chronic medical conditions. Among persons with nonaffective psychoses, higher levels of negative symptoms predicted mobility limitations. CONCLUSION: Self-reported mobility limitations are prevalent already at a young age in persons with schizophrenia and other nonaffective psychotic disorders, and among older persons with these disorders both self-reported limitations and measured performance tests show lower capacity in mobility. Difficulties in mobility are associated with negative symptoms. Mental health care professionals should pay attention to mobility limitations in persons with psychotic disorder.     

Physical function and fitness in long-term survivors of childhood leukaemia

Objective: To evaluate the physical function and fitness in survivors of childhood leukaemia 5–6 years after cessation of chemotherapy.

Materials and methods: Thirteen children (six boys and seven girls; mean age 15.5 years) who were treated for leukaemia were studied 5–6 years after cessation of therapy. Physical function and fitness were determined by anthropometry, motor performance, muscle strength, anaerobic and aerobic exercise capacity.

Results: On motor performance, seven of the 13 patients showed significant problems in the hand-eye co-ordination domain. Muscle strength only showed a significantly lower value in the mean strength of the knee extensors. The aerobic and the anaerobic capacity were both significantly reduced compared to reference values.

Conclusion: Even 5–6 years after cessation of childhood leukaemia treatment, there are still clear late effects on motor performance and physical fitness. Chemotherapy-induced neuropathy and muscle atrophies are probably the prominent cause for these reduced test results. Physical training might be indicated for patients surviving leukaemia to improve fitness levels and muscle strength.     

NF-E2-related factor 2 activation boosts antioxidant defenses and ameliorates inflammatory and amyloid properties in human Presenilin-1 mutated Alzheimer's disease astrocytes

Alzheimer's disease (AD) is a common dementia affecting a vast number of individuals and significantly impairing quality of life. Despite extensive research in animal models and numerous promising treatment trials, there is still no curative treatment for AD. Astrocytes, the most common cell type of the central nervous system, have been shown to play a role in the major AD pathologies, including accumulation of amyloid plaques, neuroinflammation, and oxidative stress. Here, we show that inflammatory stimulation leads to metabolic activation of human astrocytes and reduces amyloid secretion. On the other hand, the activation of oxidative metabolism leads to increased reactive oxygen species production especially in AD astrocytes. While healthy astrocytes increase glutathione (GSH) release to protect the cells, Presenilin-1-mutated AD patient astrocytes do not. Thus, chronic inflammation is likely to induce oxidative damage in AD astrocytes. Activation of NRF2, the major regulator of cellular antioxidant defenses, encoded by the NFE2L2 gene, poses several beneficial effects on AD astrocytes. We report here that the activation of NRF2 pathway reduces amyloid secretion, normalizes cytokine release, and increases GSH secretion in AD astrocytes. NRF2 induction also activates the metabolism of astrocytes and increases the utilization of glycolysis. Taken together, targeting NRF2 in astrocytes could be a potent therapeutic strategy in AD.     

The Janus face of thromboprophylaxis in patients with high risk for both thrombosis and bleeding during intracranial surgery: report of five exemplary cases

Background  

The antithrombotic agents are usually interrupted in fear of bleeding complications before neurosurgery. However, the optimal schematic regimen of substitutive medication to prevent thromboembolic events after surgery is unsettled.     

Evaluation of matrix metalloproteinase 7 in plasma and pancreatic juice as a biomarker for pancreatic cancer.

Differentiating between periampullary carcinoma and chronic pancreatitis with an inflammatory mass is difficult. Consequently, 6% to 9% of pancreatic resections for suspected carcinoma are done inappropriately for chronic pancreatitis. Here, we test if matrix metalloproteinase 7 (MMP-7), a secreted protease frequently expressed in pancreatic carcinoma, can be measured in plasma, pancreatic, and duodenal juice, and if it can distinguish between periampullary carcinoma and chronic pancreatitis. Ninety-four patients who underwent pancreatic surgery for a (peri)pancreatic neoplasm (n = 63) or chronic pancreatitis (n = 31) were analyzed. Median plasma MMP-7 levels were significantly higher in carcinoma (1.95 ng/mL; interquartile range, 0.81-3.22 ng/mL) compared with chronic pancreatitis and benign disease (0.83 ng/mL; interquartile range, 0.25-1.21 ng/mL; P < 0.01). MMP-7 levels in pancreatic juice were higher, although not significantly, in carcinoma (62 ng/mg protein; interquartile range, 18-241 ng/mg protein) compared with chronic pancreatitis and benign disease (23 ng/mg protein; interquartile range, 8.5-99 ng/mg protein; P = 0.17). MMP-7 levels in duodenal juice were universally low. At an arbitrary cutoff of 1.5 ng/mL in plasma, positive and negative predictive values were 83% and 57%, respectively, values comparable to those of today's most common pancreatic tumor marker, carbohydrate antigen 19-9 (CA19-9; 83% and 53%, respectively). Positive and negative likelihood ratios for plasma MMP-7 were 3.35 and 0.52, respectively. The area under the receiver operating characteristic curve for MMP-7 was 0.73 (95% confidence interval, 0.63-0.84) and for CA19-9, 0.75 (95% confidence interval, 0.64-0.85). Combined MMP-7 and CA19-9 assessment gave a positive predictive value of 100%. Thus, plasma MMP-7 levels discriminated between patients with carcinoma and those with chronic pancreatitis or benign disease. The diagnostic accuracy of plasma MMP-7 alone is not sufficient to determine treatment strategy in patients with a periampullary mass, but combined evaluation of plasma MMP-7 with CA19-9 and other markers may be clinically useful.     

Noise frame duration,masking potency and whiteness of temporal noise

PURPOSE: Because of the limited contrast range, increasing the duration of the noise frame is often the only option for increasing the masking potency of external, white temporal noise. This, however, reduces the high-frequency cutoff beyond which noise is no longer white. This study was conducted to determine the longest noise frame duration that produces the strongest masking effect and still mimics white noise on the detection of sinusoidal flicker. METHODS: Contrast energy thresholds (E(th)) were measured for flicker at 1.25 to 20 Hz in strong, purely temporal (spatially uniform), additive, external noise. The masking power of white external noise, characterized by its spectral density at zero frequency N0, increases with the duration of the noise frame. RESULTS: For short noise frame durations, E(th) increased in direct proportion to N0, keeping the nominal signal-to-noise ratio [SNR = (E(th)/N0)(0.5)] constant at threshold. The masking effect thus increased with the duration of the noise frame and the noise mimicked white noise. When noise frame duration and N0 increased further, the nominal SNR at threshold started to decrease, indicating that noise no longer mimicked white noise. The minimum number of noise frames per flicker cycle needed to mimic white noise decreased with increasing flicker frequency from 8.3 at 1.25 Hz to 1.6 at 20 Hz. CONCLUSIONS: The critical high-frequency cutoff of detection-limiting temporal noise in terms of noise frames per signal cycle depends on the temporal frequency of the signal. This is opposite to the situation in the spatial domain and must be taken into consideration when temporal signals are masked with temporal noise.     

Hirschsprung's disease in cartilage-hair hypoplasia has poor prognosis

Purpose: Cartilage-hair hypoplasia (CHH) is a chondrodysplasia with growth failure, impaired immunity, and high incidence of Hirschsprung disease (HD). This study describes the outcome of CHH patients with HD. Methods: Among 147 patients with CHH, 13 were identified to have HD. Their medical records were analyzed for treatment, outcome, and complications of HD and compared with a control group of 169 patients with HD but not CHH. Results: Eight CHH patients had classic HD with rectosigmoid involvement, 2 had long segment colonic disease, and 3 patients had total colonic aganglionosis. Six of the 13 CHH patients (46%) had episodes of enterocolitis before the first surgery. Enterocolitis was complicated by colonic perforation in 2 cases. Eleven CHH patients (85%) had at least one episode of postoperative enterocolitis. Five patients (38%) with CHH and HD had died; 4 of enterocolitis-related septic infection and one of non-Hodgkin's lymphoma. In the control group, preoperative enterocolitis occurred in 14% and postoperative enterocolitis in 8%. Two controls (1.2%) had died. Conclusions: HD associated with CHH has poor prognosis in terms of postoperative morbidity and risk of death. These patients require particular attention during postoperative follow-up to detect potentially lethal complications.     

Enhanced coagulation activation in preeclampsia: the role of APC resistance,microparticles and other plasma constituents

In the Second Northwick Park Heart Study, the activation peptides of factor IX (FIXpep) and factor X (FXpep) were measured in 1261 middle-aged men by double-antibody radioimmunoassay. During follow-up 147 men who had a first coronary heart disease (CHD) event were found to have had an increased FIXpep (p = 0.003) and a reduced FXpep (p = 0.05) at baseline compared with those remaining CHD-free (controls). Plasma FIXpep and FXpep were positively associated, but the rate of rise in FIXpep with increasing FXpep was higher in cases than controls (p for interaction = 0.01). In a sample of 87 controls, FIXpep was positively and independently related to the concentrations of a polymorphonuclear-specific fibrinogen degradation product (p = 0.036) and FXpep (p = 0.004), but in larger samples no statistically significant associations were found either with C-reactive protein or with fibrinogen concentration. The findings suggested that the increased FIXpep in men at high CHD-risk may have been partly due to the generation of factor IX inactivation peptides by inflammatory proteolysis and their recognition together with true FIXpep in the radioimmunoassay. Direct evidence for this hypothesis requires development of assays for human elastase-specific factor IX inactivation peptides.