Opposite activation of the Hedgehog pathway in CD138+ plasma cells and CD138-CD19+ B cells identifies two subgroups of patients with multiple myeloma and different prognosis.

Hyperactivation of the Hedgehog (Hh) pathway, which controls refueling of multiple myeloma (MM) clones, might be critical to disease recurrence. Although several studies suggest the Hh pathway is activated in CD138- immature cells, differentiated CD138+ plasma cells might also be able to self-renew by producing themselves the Hh ligands. We studied the gene expression profiles of 126 newly diagnosed MM patients analyzed in both the CD138+ plasma cell fraction and CD138-CD19+ B-cell compartment. Results demonstrated that an Hh-gene signature was able to cluster patients in two subgroups characterized by the opposite Hh pathway expression in mature plasma cells and their precursors. Strikingly, patients characterized by Hh hyperactivation in plasma cells, but not in their B cells, displayed high genomic instability and an unfavorable outcome in terms of shorter progression-free survival (hazard ratio: 1.92; 95% confidence interval: 1.19-3.07) and overall survival (hazard ratio: 2.61; 95% confidence interval: 1.26-5.38). These results suggest that the mechanisms triggered by the Hh pathway ultimately led to identify a more indolent vs a more aggressive biological and clinical subtype of MM. Therefore, patient stratification according to their molecular background might help the fine-tuning of future clinical and therapeutic studies.

Metacognition as a mediator of the effects of impairments in neurocognition on social function in schizophrenia spectrum disorders.

OBJECTIVE: This study explored whether Mastery, a domain of metacognition that reflects the ability to use knowledge about mental states to respond to psychological challenges, mediated the effects of neurocognition on the frequency of social contact and persons' capacity for social relatedness. METHOD: Participants were 102 adults with schizophrenia or schizoaffective disorder. Neurocognition was represented by a single factor score produced by a principal components analysis of a neurocognitive test battery. Mastery was assessed using the metacognitive assessment scale and social functioning by the quality of life scale. RESULTS: Using structural equation modeling, specifically measured-variable path analysis, a mediational model consisting of neurocognitive capacity linked to mastery and capacity for social relationships and mastery linked with frequency of social contact and capacity for social relatedness showed acceptable fit to the observed data. This persisted after controlling for negative and cognitive symptoms. CONCLUSION: Results suggest that certain forms of metacognition mediate the influence of neurocognition upon function in schizophrenia.

Metacognition amidst narratives of self and illness in schizophrenia: associations with neurocognition, symptoms, insight and quality of life.

OBJECTIVE: Impairments in laboratory tasks of metacognition appear to be associated with symptoms, functioning, and neurocognition in schizophrenia. We sought to replicate these results in a study of metacognition within personal narratives of self and illness. METHOD: Narratives of 61 men with schizophrenia were rated using the Metacognition Assessment Scale and correlated with concurrent assessment of symptoms, quality of life, neurocognition and insight. RESULTS: Controlling for age and education, understanding of one's own mind was linked with better neurocognition across multiple domains, and lesser emotional withdrawal. Greater understanding of other's mind was linked with better verbal memory and less emotional withdrawal. Greater metacognition in the context of purposeful problem solving was associated with better verbal memory, insight and social function, and less emotional withdrawal and paranoia. CONCLUSION: Deficits in metacognition within the narratives of persons with schizophrenia are linked with symptoms, quality of life, neurocognition and poorer awareness of illness.