No abstract

The deficit in ability to attribute mental states such as thoughts, beliefs, and intentions of another person is a key component in the functional impairment of social cognition in schizophrenia. In the current study, we compared the ability of persons with first episode schizophrenia (FE-SZ) and individuals with schizophrenia displaying symptomatic remission (SZ-CR) to decode the mental state of others with healthy individuals and schizoaffective patients. In addition, we analyzed the effect of dopamine-related genes polymorphism on the ability to decode the mental state of another, and searched for different genetic signatures. Our results show that overall, individuals with schizophrenia performed worse in the “Reading the Mind in the Eyes” (eyes) test, a simple well-defined task to infer the mental state of others than healthy individuals. Within the schizophrenia group, schizoaffective scored significantly higher than FE-SZ, SZ-CR, and healthy individuals. No difference was observed in performance between FE-SZ and SZ-CR subjects. Interestingly, FE-SZ and SZ-CR, but not schizoaffective individuals, performed worse in decoding negative and neutral emotional valance than the healthy control group. At the genetic level, we observed a significant effect of the DAT genotype, but not D4R genotype, on the eyes test performance. Our data suggest that understanding the mental state of another person is a trait marker of the illness, and might serve as an intermediate phenotype in the diagnostic process of schizophrenia disorders, and raise the possibility that DA-related DAT gene might have a role in decoding the mental state of another person.

Beta thalassemia major (βT) is a hereditary anemia characterized by transfusion-dependency, lifelong requirement of chelation, and organ dysfunction. MicroRNA (miRNA) can be packed into extracellular vesicles (EVs) that carry them to target cells. We explored EV-miRNA in βT and their pathophysiologic role. Circulating EVs were isolated from 35 βT-patients and 15 controls. EV miRNA was evaluated by nano-string technology and real-time quantitative polymerase chain reaction (RT-qPCR). We explored effects of EVs on cell culture proliferation, apoptosis, and signal transduction. Higher amounts of small EV (exosomes) were found in patients than in controls. The expression of 21 miRNA was > two-fold higher, and of 17 miRNA < three-fold lower in βT-EVs than control-EVs. RT-qPCR confirmed differential expression of six miRNAs in βT, particularly miR-144-3p, a regulator of erythropoiesis. Exposure of endothelial, liver Huh7, and pancreatic 1.1B4 cells to βT-EVs significantly reduced cell viability and increased cell apoptosis. βT-EV-induced endothelial cell apoptosis involved the MAPK/JNK signal-transduction pathway. In contrast, splenectomized βT-EVs induced proliferation of bone marrow mesenchymal stem cells (BM-MSC). In summary, the miR-144-3p was strongly increased; βT-EVs induced apoptosis and decreased endothelial, pancreatic, and liver cell survival while supporting BM-MSC proliferation. These mechanisms may contribute to βT organ dysfunction and complications.