Increased salience of gains versus decreased associative learning differentiate bipolar disorder from schizophrenia during incentive decision making.

BACKGROUND: Abnormalities in incentive decision making, typically assessed using the Iowa Gambling Task (IGT), have been reported in both schizophrenia (SZ) and bipolar disorder (BD). We applied the Expectancy-Valence (E-V) model to determine whether motivational, cognitive and response selection component processes of IGT performance are differentially affected in SZ and BD. METHOD: Performance on the IGT was assessed in 280 individuals comprising 70 remitted patients with SZ, 70 remitted patients with BD and 140 age-, sex- and IQ-matched healthy individuals. Based on the E-V model, we extracted three parameters, 'attention to gains or loses', 'expectancy learning' and 'response consistency', that respectively reflect motivational, cognitive and response selection influences on IGT performance. RESULTS: Both patient groups underperformed in the IGT compared to healthy individuals. However, the source of these deficits was diagnosis specific. Associative learning underlying the representation of expectancies was disrupted in SZ whereas BD was associated with increased incentive salience of gains. These findings were not attributable to non-specific effects of sex, IQ, psychopathology or medication. CONCLUSIONS: Our results point to dissociable processes underlying abnormal incentive decision making in BD and SZ that could potentially be mapped to different neural circuits.

Linguistic production and syntactic comprehension in schizophrenia and bipolar disorder.

OBJECTIVE: To explore linguistic abilities in schizophrenia and bipolar disorder. Specifically, the aims of this study were to: i) investigate microlinguistic (lexicon, morphology, syntax) and macrolinguistic (discourse coherence, pragmatics) dimensions of speech production and ii) evaluate syntactic comprehension skills in both schizophrenia and bipolar disorder. METHOD: Linguistic performance of 30 Italian-speaking patients with schizophrenia, 30 participants with bipolar disorder and 30 healthy controls comparable for age and educational level has been assessed using a story-telling task and a computer-based test of syntactic comprehension. RESULTS: In narrative production, compared with healthy participants, those with schizophrenia had slight problems in speech rate and deficits at both local and global discourse coherence, whereas patients with bipolar disorder showed reduced mean length of utterance. As regards syntactic comprehension, both groups of patients collected more grammatical errors than controls, but they differed with regard to the number and kind of grammatical construction they missed. CONCLUSION: Linguistic deficits have been detected in both groups of patients, being, however, more severe and generalized in schizophrenia than in bipolar disorder. Such results help us in improving our understanding of the potential psychopathological overlapping between these disorders.

A new nonsense mutation of the IGHMBP2 gene responsible for the first case of SMARD1 in a Sardinian patient with giant cell hepatitis.

We describe the case of a Sardinian female child affected by SMARD1, a genetic composite heterozygote, in whom a new nonsense mutation (R788X) was found. A sister was affected by generalized muscular hypotonia and died from respiratory insufficiency at the age of 9 months, before a diagnostic definition had been formulated. Our patient died at 6 months due to respiratory insufficiency. At autopsy some differences with previous published cases were observed. In fact, our case is to the best of our knowledge the first report of giant cell hepatitis and myocarditis in SMARD1-affected patients, although this could be a chance association.

Progressive disability and prefrontal shrinkage in schizophrenia patients with poor outcome: A 3-year longitudinal study.

INTRODUCTION: Schizophrenia is a severe disabling disorder with heterogeneous illness courses. In this longitudinal study we characterized schizophrenia patients with poor and good outcome (POS, GOS), using functional and imaging metrics. Patients were defined in accordance to Keefe's criteria (i.e. Kraepelinian and non-Kraepelinian patients). METHODS: 35 POS patients, 35 GOS patients and 76 healthy controls (H) underwent clinical, functioning and magnetic resonance imaging (MRI) assessments twice over three years of follow-up. Information on psychopathology, treatment, disability (using the World Health Organization Disability Assessment Scale II, WHO-DAS-2) and prefrontal morphology was collected. Dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) were manually traced. RESULTS: At baseline, subjects with POS showed significantly decreased right dorsolateral prefrontal cortex (DLPFC) white matter volumes (WM) compared to healthy controls and GOS patients (POS VS HC, p<0.001; POS vs GOS, p=0.03), with shrinkage of left DLPFC WM volumes at follow up (t=2.66, p=0.01). Also, POS patients had higher disability in respect to GOS subjects both at baseline and after 3years at the WHO-DAS-2 (p<0.05). DISCUSSION: Our study supports the hypothesis that POS is characterized by progressive deficits in brain structure and in "real-life" functioning. These are particularly notable in the DLPFC.

Interindividual variability in the expression of surfactant protein A and B in the human lung during development.

The surfactant complex, thanks to its multiple actions including decrease of surface- tension and antimicrobial activity, plays a fundamental role in newborn survival, lowering the risk of respiratory distress syndrome. The aim of this work was to determine if the synthesis of two surfactant proteins (SP), SPA and pro-SPB, shows some inter-individual variability during lung development in the intrauterine life. Immunoreactivity for SPA and pro-SPB was investigated in the lungs of  40 subjects, including 15 fetuses, ranging from 14 to 22 weeks of gestation, and 25 neonates, from 24 to 41 weeks. Lung samples were formalin fixed, paraffin-embedded and routinely processed. SPA and pro-SPB were detected utilizing commercial antibodies.  A semi-quantitative grading system (1 to 4) was applied, based on the number of reactive cells and the intensity of immunostaining. Surfactant protein immunostaining was found in  three compartments: bronchi, bronchioles and alveoli, starting from 14 weeks of gestation in the bronchial epithelium and from the 21st week in the alveolar spaces. Differences were found regarding SPA and pro-SPB expression in the vast majority of subjects: in some lungs, SPA was more expressed whereas in others pro-SPB showed an higher degree of immunoreactivity. The expression of both surfactant proteins was not strictly correlated with gestational age. Whereas the highest levels of reactivity were detected in at term neonates, on the other hand one case with grade 3 was detected at 22 weeks and one negative case for both proteins was observed at 31 weeks. Our data clearly show a marked inter-individual variability regarding the production of SPA and pro-SPB and suggest the existence of other epigenetic factors, acting during gestation, that might influence surfactant production and, consequently, the survival potential of  neonates at birth.

Antimycins, inhibitors of ATP-citrate lyase, from a Streptomyces sp.

A related group of compounds belonging to the antimycin class of antibiotics was found in culture broth produced by a Streptomyces species. The group includes known antimycins A1, A2, A3 and A4, and new antimycins A7 and A8. These compounds inhibit ATP-citrate lyase with Ki values of 4 to 60 microM against the substrate magnesium citrate. The structures of the new antimycins were determined by spectroscopic analyses.

Therapeutic embolization of polycystic kidneys.

In two patients with end-stage polycystic kidneys suffering from severe and protracted hematuria recourse was made to therapeutic renal embolization. Hematuria stopped immediately, never to appear again, whilst recanalization of the arterial renal circulation was observed later. Since the therapeutic embolization of kidneys in patients with end-stage uremia is exceedingly risky and, therefore, unadvised, it is regarded only in the case of a bleeding polycystic kidney as implementable and more effective than nephrectomy.

Increased M1/decreased M2 signature and signs of Th1/Th2 shift in chronic patients with bipolar disorder, but not in those with schizophrenia.

We here present data on immune gene expression of chemokines, chemokine receptors, cytokines and regulatory T-cell (T-reg) markers in chronic patients suffering from either schizophrenia (SCZ, N=20) or bipolar disorder (BD=20) compared with healthy controls (HCs, N=20). We extracted RNA from peripheral blood mononuclear cells and performed real-time (RT)-PCR to measure mRNA levels of chemokines, chemokine receptors, cytokines and T-reg markers. All the analyses were Bonferroni-corrected. The classical monocyte activation (M1) markers il6, ccl3 were significantly increased in BD as compared with both HC and SCZ patients (P=0.03 and P=0.002; P=0.024 and P=0.021, respectively), whereas markers of alternative (M2) monocyte activation ccl1, ccl22 and il10 were coherently decreased (controls: P=0.01, P=0.001 and P=0.09; SCZ subjects: P=0.02, P=0.05 and P=0.011, respectively). Concerning T-cell markers, BD patients had compared with HC downregulated ccr5 (P=0.02) and upregulated il4 (P=0.04) and compared with both healthy and SCZ individuals downregulated ccl2 (P=0.006 and P=0.003) and tgfß (P=0.004 and P=0.007, respectively). No significant associations were found between any immune gene expression and clinical variables (prior hospitalizations, Brief Psychiatric Rating Scale, medications' dosages and lifetime administration). Although some markers are expressed by different immune cell types, these findings suggest a coherent increased M1/decrease M2 signature in the peripheral blood of BD patients with potential Th1/Th2 shift. In contrast, all the explored immune marker levels were preserved in SCZ. Further larger studies are needed to investigate the relevance of inflammatory response in BD, trying to correlate it to psychopathology, treatment and outcome measures and, possibly, to brain connectivity.

CD10 in the developing human kidney: immunoreactivity and possible role in renal embryogenesis.

CD10 was first identified in tumor cells of acute lymphoblastic leukemia. Most studies on CD10 expression have dealt with tumor pathology. Since no data are available for specific role in the fetal kidney, this study aimed at investigating CD10 expression during the different phases of renal embryogenesis. To this end, the expression of CD10 was evaluated in the kidney of two human fetus and in three newborns. In both fetuses, immunostaining for CD10 was compartmentalized and mainly concentrated in the mid-deep cortex. Reactivity for CD10 was stronger in the glomerular epithelium, in proximal tubules and in metanephric mesenchymal cells. At 25 weeks of gestation, CD10 was also detected in the subcapsular regions, including some pretubular aggregates of cap mesenchymal cells and renal vesicles. At 34 weeks of gestation, we observed an increased immunoreactivity for CD10 in visceral and parietal glomerular epithelium. At 39 weeks of gestation, CD10 was also expressed in the collecting tubules and in the Henle loops. Our data show a strong expression of CD10 in all stage of human kidney development, characterized by dynamic changes and support the hypothesis that CD10 plays a relevant role in renal embryogenesis.

An optic micro-switch for an eyelid response to foster environmental control in children with minimal motor behaviour.

This study assessed whether two children (11.9- and 9.7-years-old) with profound multiple disabilities and minimal motor behaviour could learn to control environmental stimulation using an eyelid response with a newly developed micro-switch. The response consisted of raising the eyelid markedly (i.e. by looking upward or opening the eyes widely). The micro-switch developed for this target response consisted of an electronically regulated optic sensor mounted on an eyeglasses' frame. Data showed that the children learned the target eyelid response to activate the micro-switch and to increase their level of environmental stimulation. Responding was largely maintained at a 2-month post-intervention check. These results indicate that continued work in this area has positive implications for the rehabilitation of children with most serious disabilities.