Working memory impairments in first-episode psychosis and chronic schizophrenia

Working memory (WM) impairments are core cognitive deficits in patients with schizophrenia linked to prefrontal cortical dysfunctions. Determining the differences between early phases of illness allows a better understanding of its course and constitutes an important guide for treatment. The present cross-sectional study examined differences of working memory functions between 33 first-episode and 29 chronic schizophrenic patients, as well as 64 healthy controls. On the basis of a two-back visual–verbal computerized working memory task, reaction time was slower and accuracy was worse in both patient groups than in controls. Test variables, however, were not significantly different between the patient groups, suggesting stability of the deficits over time. Effect size accuracy variables nevertheless showed larger deficits in chronic patients.     

An empirical test of the concomitantly variable codon hypothesis

A central assumption of models of molecular evolution, that each site in a sequence evolves independently of all other sites, lacks empirical support. We investigated the extent to which sites evolve codependently in triosephosphate isomerase (TIM), a ubiquitous glycolytic enzyme conserved in both structure and function. Codependencies among sites, or concomitantly variable codons (covarions), are evident from the reduced function and misfolding of hybrid TIM proteins. Although they exist, we find covarions are relatively rare, and closely related proteins are unlikely to have developed them. However, the potential for covarions increases with genetic distance so that highly divergent proteins may have evolved codependencies between many sites. The evolution of covarions undermines a key assumption in phylogenetics and calls into question our ability to disentangle ancient relationships among major taxonomic groups.     

Dehydroepiandrosterone secretion in dairy cattle is episodic and unaffected by ACTH stimulation

This paper describes the episodic release and response to adrenal stimulation of cortisol and dehydroepiandrosterone (DHEA) in cows. Observations made in samples taken every 10 min for 8 h (experiment 1) showed that plasma DHEA was significantly greater (P < 0.001) than DHEA-S, and release of these steroids was episodic and variable between animals (P < 0.01). No relationship was found between DHEA and cortisol. Significant (P < 0.001) DHEA-sulphate (DHEA-S) versus cortisol (R = -0.264) and DHEA-S versus DHEA (R = 0.200) correlations were found. DHEA and DHEA-S were not affected by a single ACTH challenge (experiment 2). In experiment 3, cortisol and DHEA secretions in response to prolonged ACTH administration (every 12 h for 6 days) were studied. On day 7, the episodic cortisol and DHEA release and response to the opioid antagonist naloxone were studied in blood samples taken every 10 min for 8 h. Animals were injected with naloxone after 4 h. A significant increase (P < 0.05) in mean circulating DHEA and DHEA pulse amplitude was observed during frequent sampling following ACTH treatment. DHEA and DHEA-S plasma concentrations were not affected following luteal regression (experiment 4). The effect of milk secretion around parturition on DHEA secretion was studied in dry and continuously milked cows (experiment 5). Plasma DHEA was significantly lower (P < 0.05) in milked cows. In the cow, ACTH is not an important DHEA secretagogue. Adrenal contribution to plasma DHEA is scarce. Likely, the placenta is the most important source of DHEA, and the lactating mammary gland can affect circulating DHEA levels. Investigation about the DHEA biological role in cows should be focused around parturition.     

Astrocyte-like cells as a main target for estrogen action during neuronal differentiation

Neurospheres from the subventricular zone of adult mice were used as an experimental model to analyse the early differential effects of 17beta-estradiol (17beta-E2). Both floating and differentiating neurospheres expressed estrogen receptors (ERs) alpha and beta. The initial phases of differentiation coincided with a peak of ERalpha expression as by Western blot analysis. Treatment with 10 nM 17beta-E2 induced a significant increase in the glial fibrillary acidic protein (GFAP)-positive population and a greater expression of GFAP, an effect sensitive to the estrogen receptor antagonist ICI 182,780. The GFAP-positive cell population induced by 17beta-E2 was characterized by a highly differentiated phenotype and intense immunostaining as by immunocytochemistry and flow cytometry. These cells co-expressed ERalpha and were positive to BrdU. 17beta-E2 also affected neuronal differentiation by rapidly and transiently increasing the percentage of polysialylated-neural cell adhesion molecule (PSA-NCAM)-positive progenitors, and by accelerating the appearance of a mature neuronal phenotype, as evaluated by microtubule-associated protein 2 (MAP2) staining. Our results point to a key role for ERalpha during initial phases of differentiation of brain cells and to an effect of 17beta-E2 that sequentially involves both glia and neurons.     

Visual scan paths in first-episode schizophrenia and cannabis-induced psychosis

OBJECTIVE: Patterns of successive saccades and fixations (scan paths) that are made while viewing images are often spatially restricted in schizophrenia, but the relation with cannabis-induced psychosis has not been examined. We used higher-order statistical methods to examine spatiotemporal characteristics of scan paths to determine whether viewing behaviour was distinguishable on a continuum. METHODS: Patients with early acute first-episode paranoid schizophrenia (SCH; n = 11), cannabis-induced psychosis (CIP; n = 6) and unaffected control subjects (n = 22) undertook a task requiring free viewing of facial, fractal and landscape images for 5 seconds while their eye movements were recorded. Frequencies and distributions of saccades and fixations were calculated in relation to image regions examined during each trial. RESULTS: Findings were independent of image category, indicating generalized scanning deficits. Compared with control subjects, patients with SCH and CIP made fewer saccades and fewer fixations of longer duration. In turn, the spatial distribution of fixations in CIP patients was more clustered than in SCH and control subjects. The diversity of features fixated in subjects with CIP was also lower than in SCH patients and control subjects. CONCLUSION: A continuous approach to characterizing scan path changes in different phenotypes suggests that CIP shares some of the abnormalities of SCH but can be distinguished with measures that are sensitive to cognitive strategies active or inhibited during visual exploration.     

Differential expression of constitutive and inducible proteasome subunits in human monocyte‐derived DC differentiated in the presence of IFN‐α or IL‐4

Several studies strongly suggest that DC differentiated in vitro in the presence of type I IFN acquire more potent immune stimulatory properties, compared with DC differentiated in vitro with IL‐4. However, little is known about the molecular mechanisms underlying this phenomenon. To address this question, we compared the Ag‐processing machinery (APM) profile in human DC grown in the presence of IFN‐α (_IFNDC) or IL‐4 (_IL‐4DC). Using a panel of APM component‐specific mAb in Western blot experiments, we found that _IFNDC preferentially express inducible proteasome subunits (LMP2, LMP7, and MECL1) both at immature and mature stages. In contrast, immature _IL‐4DC co‐express both constitutive (β1, β2, and β5) and inducible subunits, as shown by Western blotting analysis. In addition, immature _IFNDC express higher levels of TAP1, TAP2, calnexin, calreticulin, tapasin, and HLA class I molecules than _IL‐4DC. The different proteasome profiles of _IFNDC and _IL‐4DC were associated with a greater ability of _IFNDC to present an immunodominant epitope that requires LMP7 expression for its processing. In general, these data show the impact of cytokines on APM component expression and hence the Ag‐processing ability of DC.