Contrasting Metacognitive, Emotion Recognition and Alexithymia Profiles in Bulimia, Anorexia, and Schizophrenia.

ABSTRACT: Alexithymia, or deficits in emotion recognition, and metacognitive capacity have been noted both in psychosis and eating disorders and potentially linked to psychopathology. This study sought to compare levels of impairments in these phenomena and their associations with psychopathology in groups with eating disorders and psychosis. Participants with diagnoses of a schizophrenia spectrum disorder (SSD; n = 53), anorexia (n = 40), or bulimia (n = 40) were recruited from outpatient clinics. Alexithymia was measured with the Toronto Alexithymia Scale; emotion recognition, with the Ekman Faces Test; and metacognition, with the Metacognitive Assessment Scale-Abbreviated. Psychopathology was measured with the Eating Attitudes Test, Body Image Questionnaire, and Positive and Negative Syndrome Scale. Results indicated that the SSD group had significantly poorer metacognitive function than either eating disorder group. Metacognition was related to body image in the anorexia group and a range of different forms of general psychopathology in the bulimia group. Alexithymia was related to eating disorder behaviors in the bulimia group.

The association of metacognition with emotion recognition and perspective taking in a Russian sample with psychosis.

OBJECTIVE: Schizophrenia may reflect an interactive network of disturbances in cognition. In this study we have examined the relationship between two forms of cognition: metacognition and social cognition among a sample with schizophrenia (n = 41), early episode psychosis (n = 37), and major depression (n = 30) gathered in Moscow, Russia. METHODS: Metacognition was assessed with the Metacognition Assessment Scale-Abbreviated. Social cognition was assessed with the Ekman 60 Faces Test and the Interpersonal Reactivity Index. Verbal memory and global psychopathology were included as potential covariates. RESULTS: Partial correlations controlling for demographics, neurocognition, and psychopathology revealed greater metacognitive capacity was linked to better facial emotion recognition and perspective taking in the prolonged schizophrenia group. Greater metacognitive capacity in the early psychosis group was linked with greater facial emotion recognition. Metacognition and social cognition were not related to one another in the depression group. CONCLUSIONS: Social cognition and metacognition may be uniquely related in psychosis.

The paradoxical moderating effects of metacognition in the relationships between self-esteem, depressive symptoms, and quality of life in anorexia and bulimia.

BACKGROUND: Self-esteem and depressive symptoms contribute to a lower quality of life in people suffering from eating disorders. However, limited research has examined whether other factors may affect how these variables influence one another over time. Metacognition is a previously unexplored determinant that may impact the relationships between self-esteem, depressive symptoms, and quality of life in instances of eating disorders. AIM: This study sought to examine metacognitive self-reflectivity and mastery as moderators of the relationships between self-esteem, depressive symptoms, and quality of life and to determine if these relationships are different in people with anorexia compared with people with bulimia. METHODS: Participants with anorexia (n=40) and bulimia (n=40) were recruited from outpatient clinics. The participants were assessed on their metacognitive ability and self-reported on measures to assess their depressive symptoms, self-esteem, and quality of life. RESULTS: The results indicate that metacognitive self-reflectivity moderates the relationship between self-esteem, depressive symptoms, and quality of life in people with anorexia such that when self-reflectivity is high, lower self-esteem and higher depressive symptoms are associated with a lower quality of life. These relationships did not appear to be significant when self-reflectivity was low. In contrast, in the anorexia and bulimia groups, metacognitive mastery appeared to moderate the relationships between self-esteem, depressive symptoms, and quality of life such that when mastery was low, lower self-esteem and higher depressive symptoms were associated with a lower quality of life. These relationships did not appear significant when mastery was high. CONCLUSION: Metacognitive self-reflectivity and mastery seem to play paradoxical moderating roles in the relationships between self-esteem, depressive symptoms, and quality of life in people with anorexia and bulimia. These findings pave the way toward further research and have important clinical implications.

Clinical insight, cognitive insight and metacognition in psychosis: Evidence of mediation.

OBJECTIVE: Schizophrenia is increasingly understood as an interactive network of disturbances in different elements of self-awareness. In this study we have examined the relationship between disturbances in two forms of awareness: cognitive insight and clinical insight by exploring whether their relationship is mediated by a third form of larger awareness: metacognition. METHODS: Participants were 41 outpatients with schizophrenia and 37 outpatients with early episode psychosis gathered in Moscow, Russia. Metacognition was assessed with the Metacognition Assessment Scale - Abbreviated. Verbal memory and positive symptoms were assessed for use as additional mediators. RESULTS: Mediation analyses revealed that after accounting for the effects of positive symptoms and verbal memory, the relationship between the self-reflection domain of cognitive insight and clinical insight was significantly mediated by overall metacognitive capacity. Further, positive symptoms were a significant mediator between the cognitive insight self-reflection domain and clinical insight. Neither metacognition nor positive symptoms or verbal memory were found to mediate the relationship of the cognitive insight domain of self-certainty with clinical insight. CONCLUSIONS: Decrements in some forms of ability to reflect upon one's thinking may reduce the ability to form complex and integrated ideas of oneself and others, leading to less coherent and complete accounts of the experience of schizophrenia.

Inhibitor of BRAFV600E Mutation as a Treatment Option for Hairy Cell Leukemia With Deep Neutropenia and Infectious Complications.

Standard therapy in hairy cell leukemia (HCL) is often impossible at the time of deep neutropenia/agranulocytosis with or without infectious complications; it is thus a complex therapeutic problem. Vemurafenib has been used to treat resistant HCL since 2012. Because vemurafenib does not have a myelotoxic effect, we thought that it could be used to treat HCL associated with deep neutropenia/agranulocytosis with or without the development of infectious complications as a preliminary stage before treatment with cladribine. We conducted a retrospective analysis of treatment with vemurafenib followed by a standard course of cladribine provided to 22 patients with deep neutropenia/agranulocytosis with or without infectious complications at diagnosis. Vemurafenib was provided to 22 patients with HCL. The response to therapy was evaluated by complete blood cell count (absolute neutrophil count [ANC], hemoglobin concentration, platelet count, absence of hairy cells), spleen size (assessed by ultrasound), and reduce infectious complications. After that, a standard course of cladribine was provided. Among the 22 patients, the male/female sex ratio was 2:1, and median (range) age was 52 (24-78) years. There were 7 patients with severe infectious manifestations admitted to the intensive care unit, including 1 patient during extracorporeal membrane oxygenation. The median (range) ANC at diagnosis was 0.3 (0.04-0.7) × 109/L. Vemurafenib was provided at a dosage of 240 mg 1 or 2 times a day. In 20 patients, vemurafenib was provided for 3 months or more. In 1 case, the effect was not obtained during 1 month of treatment, and the patient died from severe infectious complications during prolonged agranulocytosis. In 21 patients treated with vemurafenib, an increase of ANC was observed and the infectious complications resolved, thus allowing the application of cladribine therapy. After a standard course (0.1 mg/kg per day for 7 days) of cladribine chemotherapy, 18 patients (90%) experienced complete clinical remission and 2 patients (10%) experienced partial remission with residual splenomegaly. In 1 patient, vemurafenib therapy was still ongoing 2 months after initiating therapy. In cases of proven BRAFV600E mutation, vemurafenib can be successfully used as an effective preliminary therapy in patients with deep neutropenia/agranulocytosis with or without infectious complications before standard therapy with purine analogs.

Diagnostic significance of flow cytometry scales in diagnostics of myelodysplastic syndromes.

BACKGROUND: Myelodysplastic syndromes (MDS) can present a challenge for clinicians. Multicolor flow cytometry (MFC) can aid in establishing a diagnosis. The aim of this study was to determine the optimal MFC approach for MDS. METHODS: The study included 102 MDS (39 low-grade MDS), 83 cytopenic patients without myeloid neoplastic disorders (control group), and 35 healthy donors. Bone marrow was analyzed using a six-color MFC. Analysis was conducted according to the "Ogata score," "Wells score," and the integrated flow cytometry (iFC) score. RESULTS: The respective sensitivity and specificity values were 77.5% and 90.4% for the Ogata score, 79.4% and 81.9% for the Wells score, and 87.3% and 87.6% for the iFC score. Specificity was not 100% due to deviations of MFC parameters in the control group. Patients with paroxysmal nocturnal hemoglobinuria (PNH) had higher levels of CD34+ CD7+ myeloid cells than donors. Aplastic anemia and PNH were characterized by a high proportion of CD56+ cells among CD34+ precursors and neutrophils. The proportion of MDS-related features increased with the progression of MDS. The highest number of CD34+ blasts was found in MDS with excess blasts. MDS with isolated del(5q) was characterized by a high proportion of CD34+ CD7+ cells and low granularity of neutrophils. In 39 low-grade MDS, the sensitivities were 53.8%, 61.5%, and 71.8% for Ogata score, Wells score, and iFC, respectively. CONCLUSION: The results support iFC as a useful diagnostic tool in MDS.

Contrasting metacognitive profiles and their association with negative symptoms in groups with schizophrenia, early psychosis and depression in a Russian sample.

Research has suggested that negative symptoms in psychotic disorders may be in part fueled by deficits in metacognition or the ability to form integrated ideas about oneself and others. One limitation of this work is that it has largely come from North America and Western Europe. To further the literature, we assessed symptoms using the Positive and Negative Syndrome Scale and Metacognition using the Metacognitive Assessment Scale - Abbreviated in a sample of outpatients with prolonged schizophrenia (n = 41), early episode psychosis (n = 37) and major depression (n = 30) gathered in Moscow, Russia. Verbal memory was assessed for use as a potential covariate. ANOVA revealed the two groups with psychosis had significantly poorer metacognitive function in terms of self-reflectivity and awareness of the other, than the group with depression. In both psychosis groups negative symptoms were more robustly related to metacognition than other forms of symptoms after controlling for neurocognition. Results support the possibility that metacognitive deficits are a psychological factor which cross culturally contributes to negative symptoms and point to metacognition as a potentially important target for intervention.

Role of proteasomes in transcription and their regulation by covalent modifications.

The 26S proteasome is an abundant multi-subunit complex, which, in addition to lysosomes, represents a major cellular "protein degradation factory". The proteasome complex possesses protease, ATPase/helicase, and RNAse enzymatic activities, which are used by the latter to regulate various physiological processes. Recent findings have revealed an important role of proteasomes in transcriptional regulation. Although proteasomes are well documented to undergo various post-translational modifications, little is known about their functional significance, in particular in the process of gene regulation in response to various forms of stress. Here, we review the data on the role of proteasomes in gene regulation and their post-translational modifications as well as discuss potential mechanisms by which proteasomal activity may be regulated by genotoxic stress.

Regulation of Endoribonuclease Activity of Alpha-Type Proteasome Subunits in Proerythroleukemia K562 Upon Hemin-Induced Differentiation.

The proteasome is the main intracellular proteolytic machine involved in the regulation of numerous cellular processes, including gene expression. In addition to their proteolytic activity, proteasomes also exhibit ATPase/helicase (the 19S particle) and RNAse (the 20S particle) activities, which are regulated by post-translational modifications. In this report we uncovered that several 20S particle subunits: α1 (PSMA6), α2 (PSMA2), α4 (PSMA7), α5 (PSMA5), α6 (PSMA1) and α7 (PSMA3) possess RNAse activity against the p53 mRNA in vitro. Furthermore, we found that the RNAse activity of PSMA1 and PSMA3 was regulated upon hemin-induced differentiation of K562 proerythroleukemia cells. The decrease in RNAse activity of PSMA1 and PSMA3 was paralleled by changes in their status of phosphorylation and ubiquitylation. Collectively, our data support the notion that proteasomal RNAse activity may be functionally important and provide insights into the potential mechanism of p53 repression in erythroleukemia cells by RNAse activity of the 20S α-type subunits.