The interplay of Criterion A of the Alternative Model for Personality Disorders, mentalization and resilience during the COVID-19 pandemic

Background and aims: The COVID-19 pandemic has been accompanied by a worsening of mental health levels in some, while others manage to adapt or recover relatively quickly. Transdiagnostic factors such as personality functioning are thought to be involved in determining mental health outcomes. The present study focused on two constructs of personality functioning, Criterion A of the Alternative Model for Personality Disorders (AMPD, DSM-5) and mentalization, as predictors of depressive symptoms and life satisfaction during the COVID-19 pandemic. A second focus of the study was to examine whether this relationship was mediated by resilience. Methods: Linear regression analyses were used to examine the relationship between personality functioning measured by Criterion A (AMPD, DSM-5) and mentalizing abilities as predictors, and depression and life satisfaction as mental health outcomes. To assess the hypothesis that this relationship is mediated by resilience a structural equation modeling approach was conducted. Data from N = 316 individuals from the general population were collected. Results: Linear regression models revealed highly significant associations between Criterion A/mentalization and both outcome measures. Structural equation models showed a significant partial mediation by resilience of these relationships. Conclusion: Our results support the hypothesis that mentalizing serves as a protective function by promoting resilience to the impact of stress and threats. Criterion A and mentalization performed similarly as predictors of mental health outcomes, providing empirically overlapping operationalizations of personality functioning. This finding emphasizes the importance of personality functioning in positive and negative mental health outcomes. Furthermore, our results are consistent with a mediating role of resilience

Cognitions in antisocial personality and their association with “dark” traits

Unlike those associated with depressive symptoms, little is known about cognitions associated with antisocial personality and with its related traits (“dark traits”). Using the Scrambled Sentences Task, an instrument from depression research, we investigated cognitions such as justifications (external blaming for one’s behavior) and harm to others (based on the notion that some of these individuals enjoy harming or humiliating others) that we hypothesized may be prevalent in antisocial personality. Confirming our hypothesis, these cognitions were associated with ratings in different antisocial personality scales and with antisocial and detachment scores in the Alternative Model of Personality Disorders of the DSM-5 (AMPD) in three non-clinical samples, but not with depressive symptoms or neuroticism. Cognitions including harm to others were differentially associated with high sadism. These findings characterize empirically cognitions classes that are shared by all individuals with antisocial tendencies, and that differ from those associated with depressiveness

The interaction between eukaryotic initiation factor 1A and eIF5 retains eIF1 within scanning preinitiation complexes

Scanning of the mRNA transcript by the preinitiation complex (PIC) requires a panel of eukaryotic initiation factors including eIF1 and eIF1A, the main transducers of stringent AUG selection. eIF1A plays an important role in start codon recognition; however, its molecular contacts with eIF5 are unknown. Using NMR, we unveil eIF1A’s binding surface on the carboxyl-terminal domain of eIF5 (eIF5-CTD). We validated this interaction by observing that eIF1A does not bind to an eIF5-CTD mutant, altering the revealed eIF1A-interaction site. We also found that the interaction between eIF1A:eIF5-CTD is conserved between human and yeast. Using GST pull down assays of purified proteins, we showed that the N-terminal tail (NTT) of eIF1A mediates the interaction with eIF5-CTD and eIF1. Genetic evidence indicates that overexpressing eIF1 or eIF5 suppresses the slow growth phenotype of eIF1A-NTT mutants. These results suggest that the eIF1A:eIF5-CTD interaction during scanning PICs contributes to the maintenance of eIF1 within the open PIC

Translational initiation factor eIF5 replaces eIF1 on the 40S ribosomal subunit to promote start-codon recognition

33 páginas, 10 figuras, 5 tablasIn eukaryotic translation initiation, AUG recognition of the mRNA requires accommodation of Met-tRNAi in a 'PIN' state, which is antagonized by the factor eIF1. eIF5 is a GTPase activating protein (GAP) of eIF2 that additionally promotes stringent AUG selection, but the molecular basis of its dual function was unknown. We present a cryo-electron microscopy (cryo-EM) reconstruction of a yeast 48S pre-initiation complex (PIC), at an overall resolution of 3.0 Å, featuring the N-terminal domain (NTD) of eIF5 bound to the 40S subunit at the location vacated by eIF1. eIF5 interacts with and allows a more accommodated orientation of Met-tRNAi. Substitutions of eIF5 residues involved in the eIF5-NTD/tRNAi interaction influenced initiation at near-cognate UUG codonsin vivo, and the closed/open PIC conformation in vitro, consistent with direct stabilization of the codon:anticodon duplex by the wild-type eIF5-NTD. The present structure reveals the basis for a key role of eIF5 in start-codon selection.We are grateful to CG Savva, G McMullan for technical support with cryo-EM, T Darling and J Grimmett for help with computing and J Brasa for help with figures/movies. JL was supported by a FEBS postdoctoral fellowship. TH acknowledges start-up funds from the Indian Institute of Science. This work was funded by grants to from the UK Medical Research Council (MC_U105184332), Wellcome Trust Senior Investigator award (WT096570), the Agouron Institute and the Jeantet Foundation to VR; by the Department of Science and Technology, Government of India Grant [Int/NZ/P-2/13] to AKS; from the NIH (GM62128) formerly to JRL; the Human Frontiers in Science Program (RGP-0028/ 2009) to AGH, JRL and VR; and by the Intramural Research Program of the NIH (AGH, JRL).Peer reviewe