Intact associative learning in patients with schizophrenia : evidence from a Go/NoGo paradigm

Objective: Schizophrenia is associated with deficits in executive control and associative learning. In the present study, we investigated the effect of associative learning during a Go/NoGo task in healthy controls subjects and patients with schizophrenia. Methods: Thirty patients with schizophrenia and 30 age-and-gender matched healthy control subjects performed 15 blocks of training and 3 blocks of test trials. The trials consisted of responding to words denoting either living or non-living objects. In the training condition, subjects were instructed to respond by pressing the space bar (Go-task) to one of the word types (living or non-living objects), but not the other. In the test phase, the Go/NoGo mapping was reversed. Subjects were instructed to respond as quickly and as accurately as possible. Reaction times (RT) and accuracy were recorded for each trial and all subjects were debriefed upon completion of the test trials. Results: Patients with schizophrenia had significantly longer Go RTs when compared to the control group, during both training and test trials. However, the two groups did not differ on any measure of associative learning. Conclusions: Our findings suggest that associative learning is intact in schizophrenia patients during the performance of a relational Go/NoGo paradigm. (C) 2010 Elsevier B.V. All rights reserved

Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function

Thyroid hormone (TH) is critical for the maintenance of cellular homeostasis during stress responses, but its role in lung fibrosis is unknown. Here we found that the activity and expression of iodothyronine deiodinase 2 (DIO2), an enzyme that activates TH, were higher in lungs from patients with idiopathic pulmonary fibrosis than in control individuals and were correlated with disease severity. We also found that Dio2-knockout mice exhibited enhanced bleomycin-induced lung fibrosis. Aerosolized TH delivery increased survival and resolved fibrosis in two models of pulmonary fibrosis in mice (intratracheal bleomycin and inducible TGF-β1). Sobetirome, a TH mimetic, also blunted bleomycin-induced lung fibrosis. After bleomycin-induced injury, TH promoted mitochondrial biogenesis, improved mitochondrial bioenergetics and attenuated mitochondria-regulated apoptosis in alveolar epithelial cells both in vivo and in vitro. TH did not blunt fibrosis in Ppargc1a- or Pink1-knockout mice, suggesting dependence on these pathways. We conclude that the antifibrotic properties of TH are associated with protection of alveolar epithelial cells and restoration of mitochondrial function and that TH may thus represent a potential therapy for pulmonary fibrosis