Emotional Stability Interacts with Cortisol Levels before fMRI on Brain Processing of Fearful Faces

Functional-Magnetic-Imaging (fMRI) is widely adopted to investigate neurophysiological correlates of emotion processing (EP). However, studies have reported that scanning procedures in neuroimaging protocols may increase or cause anxiety and psychological distress related with the scanning, thus inducing peripheral cortisol release. These phenomena may in turn impact on brain EP. Additionally, previous findings have indicated that inter-individual differences in stress-response intensity are mediated by levels of Emotional Stability (ES), a personality trait that has been associated with brain activity during EP, especially in amygdala and prefrontal cortex (PFC). The aim of this study was to investigate the interaction between indices of stress related to anticipation of fMRI scanning and levels of ES on amygdala and PFC activity during EP. With this aim, fifty-five healthy volunteers were characterized for trait ES. Furthermore, salivary cortisol levels at baseline and soon before fMRI scanning were measured as an index of stress related to scanning anticipation. During fMRI, participants performed an explicit EP task. We found that variation in salivary cortisol (Δc) interacts with ES on left amygdala and PFC activity during EP. More in details, in the context of a higher ES, the greater the Δc, the lower the activity in left amygdala and PFC. In the context of lower ES, the opposite Δc-brain activity relationship was found. Our results suggest that the stressful potential of fMRI interacts with personality traits in modulating brain activity during EP. These findings should be taken into account when interpreting neuroimaging studies especially exploring brain physiology during EP

New insight into the catalytic -dependent and -independent roles of METTL3 in sustaining aberrant translation in chronic myeloid leukemia

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm caused by the presence of tyrosine kinase BCR-ABL1 fusion protein, which deregulate transcription and mRNA translation. Tyrosine kinase inhibitors (TKIs) are the first-choice treatment. However, resistance to TKIs remains a challenge to cure CML patients. Here, we reveal that the m(6)A methyltransferase complex METTL3/METTL14 is upregulated in CML patients and that is required for proliferation of primary CML cells and CML cell lines sensitive and resistant to the TKI imatinib. We demonstrate that depletion of METTL3 strongly impairs global translation efficiency. In particular, our data show that METTL3 is crucial for the expression of genes involved in ribosome biogenesis and translation. Specifically, we found that METTL3 directly regulates the level of PES1 protein identified as an oncogene in several tumors. We propose a model in which nuclear METTL3/METTL14 methyltransferase complex modified nascent transcripts whose translation is enhanced by cytoplasmic localization of METTL3, independently from its catalytic activity. In conclusion, our results point to METTL3 as a novel relevant oncogene in CML and as a promising therapeutic target for TKI resistant CML

Psychometric validity of the strengths and difficulties questionnaire-dysregulation profile

Background: In many severely mentally disordered children, the clinical presentation is complicated by comorbid affective and behavioral dysregulation. Recently, a highly heritable behavioral phenotype of simultaneous deviance on the anxious/depressed, attention problems, and aggressive behavior syndrome scales has been identified on the Child Behavior Checklist Dysregulation Profile (CBCL-DP). The aim of the present pilot study was to determine an equivalent to the CBCL-DP using the Strengths and Difficulties Questionnaire (SDQ). Sampling and Methods: We applied stepwise linear discriminant analyses and receiver operating characteristic (ROC) analysis to data from 543 consecutively referred children and adolescents, aged 5–17 years. The CBCL and the SDQ were completed by parents as part of the diagnostic routine. ICD-10 discharge diagnoses were established in consensus conferences. Results: A combination of five SDQ items (SDQ-Dysregulation Profile, SDQ-DP) yielded the best discrimination of children with and without CBCL-DP and classified 81.0% of the subjects correctly leading to an area under the curve of 0.93. The content of the five SDQ-DP items mirrors well the mixed behavioral phenotype of anxious-depressive, aggressive and attention problems captured by the CBCL-DP. SDQ-DP status was highly correlated with CBCL-DP status and was best defined by a SDQ-DP score ≧5. Conclusions: The psychometric properties of the SDQ-DP have been robustly tested and validated. Based on these results, clinicians may use the SDQ-DP as a useful and economical screening measure to improve the assessment, prevention, and treatment of severe dysregulation in childhood and adolescence. Future investigations should study the longitudinal stability, heritability, and genetic associations of this behavioral phenotype.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich

The complex relationship between self-reported 'personal recovery' and clinical recovery in schizophrenia

Self-reported 'personal recovery' and clinical recovery in schizophrenia (SRPR and CR, respectively) reflect different perspectives in schizophrenia outcome, not necessarily concordant with each other and usually representing the consumer's or the therapist's point of view.By means of a cluster analysis on SRPR-related variables, we identified three clusters. The first and third cluster included subjects with the best and the poorest clinical outcome respectively. The second cluster was characterized by better insight, higher levels of depression and stigma, lowest self-esteem and personal strength, and highest emotional coping. The first cluster showed positive features of recovery, while the third cluster showed negative features. The second cluster, with the most positive insight, showed a more complex pattern, a somewhat 'paradoxical' mixture of positive and negative personal and clinical features of recovery.The present results suggest the need for a characterization of persons with schizophrenia along SRPR and CR dimensions to design individualized and integrated treatment programs aimed to improve insight and coping strategies, reduce stigma, and shape recovery styles

Familial aggregation of MATRICS Consensus Cognitive Battery scores in a large sample of outpatients with schizophrenia and their unaffected relatives

Background: The increased use of the MATRICS Consensus Cognitive Battery (MCCB) to investigate cognitive dysfunctions in schizophrenia fostered interest in its sensitivity in the context of family studies. As various measures of the same cognitive domains may have different power to distinguish between unaffected relatives of patients and controls, the relative sensitivity of MCCB tests for relativeâ\u80\u93control differences has to be established. We compared MCCB scores of 852 outpatients with schizophrenia (SCZ) with those of 342 unaffected relatives (REL) and a normative Italian sample of 774 healthy subjects (HCS). We examined familial aggregation of cognitive impairment by investigating within-family prediction of MCCB scores based on probandsâ\u80\u99 scores. Methods: Multivariate analysis of variance was used to analyze group differences in adjusted MCCB scores. Weighted least-squares analysis was used to investigate whether probandsâ\u80\u99 MCCB scores predicted REL neurocognitive performance. Results: SCZ were significantly impaired on all MCCB domains. REL had intermediate scores between SCZ and HCS, showing a similar pattern of impairment, except for social cognition. Proband's scores significantly predicted REL MCCB scores on all domains except for visual learning. Conclusions: In a large sample of stable patients with schizophrenia, living in the community, and in their unaffected relatives, MCCB demonstrated sensitivity to cognitive deficits in both groups. Our findings of significant within-family prediction of MCCB scores might reflect disease-related genetic or environmental factors