Deficient inhibition of return in chronic but not first-episode patients with schizophrenia

Background

Inhibition of return (IOR) has been tested in patients with schizophrenia with contradictory results. Some studies indicated that patients with schizophrenia have normal levels of IOR; however, other studies reported delayed or blunted IOR. Inconsistency in findings might be due to differences across studies in relevant aspects associated with disease, such as heterogeneity of the disorder, different medications, onset and severity of the illness. The present study was to explore different patterns of IOR in antipsychotic medication free first-episode schizophrenia and chronic schizophrenia.

Methods

Forty two patients with first-episode schizophrenia, 44 patients with chronic schizophrenia, and 38 healthy controls were included in the study. All subjects went through a covert orienting of attention task with seven stimulus onset asynchrony (SOA) intervals (400 ms, 500 ms, 600 ms, 700 ms, 800 ms, 1200 ms and 1500 ms).

Results

Compared with healthy controls, the magnitude and onset of IOR in first-episode patients with schizophrenia were intact. However, in patients with chronic schizophrenia, there was an attenuated cuing effect especially at SOA 700 ms; in addition, there was a robust IOR until at SOAs 800 ms or above. Moreover, the illness duration and the number of psychotic episodes were significantly correlated with the validity effect at SOAs 400 ms and 600 ms.

Conclusion

Our study suggests that deficient IOR presents in chronic but not in first-episode patients with schizophrenia. IOR deficit in schizophrenia may begin during the course of illness and deteriorate over the course of illness. Our findings are consistent with the neurodegenerative model of schizophrenia.     

Short-term plasticity in excitatory synapses of the rat medial preoptic nucleus

The medial preoptic nucleus (MPN) regulates sexual behavior which is subject to experience-dependent modifications. Such modifications must depend on functional plasticity in the controlling neural circuits. Thus, MPN synapses are likely candidates for the site of alterations. The present work is a first systematic study of functional synaptic plasticity at glutamatergic synapses in the MPN. Short-term activity-dependent plasticity was investigated using a slice preparation from young male rats. The average efficacy of AMPA/kainate-receptor-mediated synaptic transmission was activity-dependent, showing a peak at a steady stimulation rate of 2 Hz. The variation in efficacy was attributed to mainly presynaptic factors since the average response amplitude was roughly paralleled by the response probability. Upon paired-pulse stimulation, paired-pulse facilitation as well as paired-pulse depression was observed. In some cases, paired-pulse facilitation as well as paired-pulse depression was recorded from an individual neuron depending on the interval between the paired stimuli. On average, paired-pulse facilitation was observed at intervals <500 ms, and paired-pulse depression at intervals in the range 1-4 s. The findings thus reveal complex activity-dependent short-term plasticity of the functional synaptic properties in the medial preoptic nucleus.     

Neural correlates of within-level and across-level attention to multiple compound stimuli

Event-related potentials (ERPs) were recorded to investigate the neural mechanisms of attention to the same or different levels of two compound letters presented concurrently in the left and right visual fields, respectively. Relative to the condition when attention was allocated to the global level of one compound stimulus and the local level of another one (across-level attention), attention to the same level of the two compound stimuli (within-level attention) increased an early positivity between 100 and 140 ms (P1) over the occipito-parietal cortex. A long-latency positivity between 320 and 560 ms (P3) over the central-parietal area was also increased in the within-level relative to across-level attention conditions. The ERP results suggest that, relative to across-level attention, within-level attention to multiple compound stimuli facilitates both early sensory-perceptual processing and late process of stimulus evaluation and identification in hierarchical analysis.     

A model-based analysis of physiological properties of the striatal medium spiny neuron

As the principal cell of the striatum, medium spiny neurons (MSNs) are closely associated with various motor dysfunctional diseases. In this paper, we describe an electric compartment model constructed in NEURON with a realistic morphology. Based on a 554-compartment computational model, we researched the influence of external current stimuli, different ions conductance, and the removal of partial dendrites on the physiological properties of the MSN. The main results are the following: (1) in the case of external current stimuli, various firing patterns appear in the MSN and the model produces a clear period-adding bifurcation phenomenon; (2) the effect of distinct types of ion channels vary and significant differences in discharge rhythm exist even among ion channels of the same type; (3) the closer the removed dendrite was to the soma, the larger the impact this had on the discharge pattern of the MSN.     

Glucose tolerance status in 510 children and adolescents attending an obesity clinic in Central Italy

Brufani C, Ciampalini P, Grossi A, Fiori R, Fintini D, Tozzi A, Cappa M, Barbetti F. Glucose tolerance status in 510 children and adolescents attending an obesity clinic in Central Italy. Childhood obesity is epidemic in developed countries and is accompanied by an increase in the prevalence of type 2 diabetes (T2DM). Aims: Establish prevalence of glucose metabolism alterations in a large sample of overweight/obese children and adolescents from Central Italy. Methods: The study group included 510 overweight/obese subjects (3–18 yr). Oral glucose tolerance test (OGTT) was performed with glucose and insulin determination. Homeostatic model assessment of insulin resistance (HOMA‐IR) and insulin sensitivity index (ISI) were derived from fasting and OGTT measurements. Beta‐cell function was estimated by insulinogenic index. Fat mass was measured by dual‐energy x‐ray absorptiometry. Results: Glucose metabolism alterations were detected in 12.4% of patients. Impaired glucose tolerance (IGT) was the most frequent alteration (11.2%), with a higher prevalence in adolescents than in children (14.8 vs. 4.1%, p < 0.001); silent T2DM was identified in two adolescents (0.4%). HOMA‐IR and glucose‐stimulated insulin levels were higher in patients with IGT than individuals with normal glucose tolerance (HOMA‐IR = 4.4 ± 2.5 vs. 3.4 ± 2.3, p = 0.001). Fat mass percentage and insulinogenic index were not different between the two groups. In multivariate analysis, age, fasting glucose, and insulin resistance influenced independently plasma glucose at 120 min of OGTT. Individuals with combined impaired fasting glucose/IGT (IFG/IGT) and T2DM were older and had reduced plasma insulin values at OGTT when compared to patients with simple IGT. Conclusions: Glucose metabolism alterations are frequently found among children and adolescents with overweight/obesity from Central Italy. Age, fasting glucose, and insulin resistance are main predictors of IGT. We suggest the use of OGTT as a screening tool in obese European adolescents.     

European Concerted Action on Anticoagulation. Correction of displayed international normalized ratio on two point-of-care test whole-blood prothrombin time monitors (CoaguChek Mini and TAS PT-NC) by independent international sensitivity index calibration

The international normalized ratio (INR) on two widely used point-of-care test (POCT) prothrombin time (PT) monitors (CoaguChek Mini and TAS PT-NC) differed considerably and also differed from the 'true' INR obtained on the same samples using a manual PT and the same species thromboplastin international reference preparation. Agreement between the displayed INR and difference from 'true' INR has been reassessed following an independent international sensitivity index (ISI) calibration of the two systems. The displayed INRs taken at seven centres were compared with 'true' INRs from the same blood donations and INRs based on the resulting ISI. The overall difference between the displayed INRs on the two monitor systems was reduced from 21.0% to 3.5%. The overall difference in mean INR of system A from the 'true' INR was reduced from 19.0% to 9.5% and of system B from 6.8% to 0.3%, but individual centre's results still showed considerable mean INR variability. Differences between overall displayed INR with the two monitor systems have been reduced by an independent multicentre calibration, and agreement with 'true' INR on the same blood samples improved. However, marked variability in mean INR at individual centres remained after ISI correction, which demonstrates the need for external quality control of individual POCT whole-blood PT monitors.     

Reliability of point-of-care prothrombin time testing in a community clinic: a randomized crossover comparison with hospital laboratory testing

The success in achieving therapeutic international normalized ratio (INR) targets in the control of warfarin using a whole-blood point-of-care testing (POCT) monitor (CoaguChek) in a community clinic was compared with hospital laboratory coagulometer prothrombin time (PT) testing in a randomized crossover study. Forty-six patients were randomized into two groups. At each visit, capillary blood was taken for the POCT monitor and venous blood for the laboratory coagulometer. In Group 1, for 6 months, dosage was based on the CoaguChek and for the second 6 months on the coagulometer. In the second group, the order was reversed. Dosages were determined using the dawn ac computer programme. Success was assessed by the percentage of time patients were maintained within the INR targets. Agreement between laboratory and monitor INR, and patient satisfaction were also assessed. Results with the POCT monitor compared well with the hospital coagulometer. Time in INR target range between the groups was similar, with 60.9% on the POCT monitor and 59.3% with the laboratory coagulometer in Group 1 and in Group 2, respectively, 64.3% and 63.4% with no significant difference in mean INR. An INR above 4.0 gave some discrepant results. International Sensitivity Index calibrations of the two test systems indicated that the INRs were dependable. Patient questionnaires showed greater satisfaction with community POCT monitoring.     

Impaired incretin secretion and pancreatic dysfunction with older age and diabetes

Objective

To estimate the impact of aging and diabetes on insulin sensitivity, beta-cell function, adipocytokines, and incretin production.

Methods

Hyperglycemic clamps, arginine tests and meal tolerance tests were performed in 50 non-obese subjects to measure insulin sensitivity (IS) and insulin secretion as well as plasma levels of glucagon, GLP-1 and GIP. Patients with diabetes and healthy control subjects were divided into the following groups: middle-aged type 2 diabetes (MA-DM), aged Type 2 diabetes (A-DM) and middle-aged or aged subjects with normal glucose tolerance (MA-NGT or A-NGT).

Results

IS, as determined by the homeostasis model assessment, glucose infusion rate, and oral glucose insulin sensitivity, was reduced in the aged and DM groups compared with MA-NGT, but it was similar in the MA-DM and A-DM groups. Insulinogenic index, first and second phase insulin secretion and the disposition indices, but not insulin response to arginine, were reduced in the aged and DM groups. Postprandial glucagon production was higher in MA-DM compared to MA-NGT. Whereas the GLP-1 production was reduced in A-DM, no differences between groups were observed in GIP production.

Conclusions

In non-obese subjects, diabetes and aging impair insulin sensitivity. Insulin production is reduced by aging, and diabetes exacerbates this condition. Aging associated defects superimposed diabetic physiopathology, particularly regarding GLP-1 production. On the other hand, the glucose-independent secretion of insulin was preserved. Knowledge of the complex relationship between aging and diabetes could support the development of physiopathological and pharmacological based therapies.