Beliefs are multidimensional and vary in stability over time - psychometric properties of the Beliefs and Values Inventory (BVI)

The cognitive processes underlying belief are still obscure. Understanding these processes may lead to more targeted treatment to better address functional impairment, such as occurs with delusions. One way in which this might be accomplished is to understand healthy, everyday beliefs, and how these may relate to characteristics observed in delusions. As yet, no such measure exists to accurately measure belief across a range of themes and dimensions. This paper outlines two studies documenting the creation and psychometric properties of a novel measure assessing three different dimensions of belief across themes of politics, science, the paranormal, religion, and morality in UK samples (n = 1, 673 total). Reliability estimates suggested good to excellent consistency (alpha > 0.8 per theme) with moderate to excellent reliability at 48 h (ICC = 0.61 –0.96) and 3.5 months (ICC = 0.61 –0.89). Factor analyses suggested good support for our five chosen themes of belief, suggesting they are distinct topic areas. Correlations across theme and dimension suggested dissociable characteristics within themes. These results have implications for 1. understanding the stability and relationship between themes of belief in a population and, 2. exploring how beliefs may change over time or as a result of an intervention. Full analysis code and data are available from the Open Science Framework (https://osf.io/hzvwr/)

Probenecid Blocks Human P2X7 Receptor-Induced Dye Uptake via a Pannexin-1 Independent Mechanism

P2X7 is a ligand-gated ion channel which is activated by ATP and displays secondary permeability characteristics. The mechanism of development of the secondary permeability pathway is currently unclear, although a role for the hemichannel protein pannexin-1 has been suggested. In this study we investigated the role of pannexin-1 in P2X7-induced dye uptake and ATP-induced IL-1β secretion from human monocytes. We found no pharmacological evidence for involvement of pannexin-1 in P2X7-mediated dye uptake in transfected HEK-293 cells with no inhibition seen for carbenoxolone and the pannexin-1 mimetic inhibitory peptide, 10Panx1. However, we found that probenecid inhibited P2X7-induced cationic and anionic dye uptake in stably transfected human P2X7 HEK-293 cells. An IC50 value of 203 μM was calculated for blockade of ATP-induced responses at human P2X7. Probenecid also reduced dye uptake and IL-1β secretion from human CD14+ monocytes whereas carbenoxolone and 10Panx1 showed no inhibitory effect. Patch clamp and calcium indicator experiments revealed that probenecid directly blocks the human P2X7 receptor

Amygdala Engagement in Response to Subthreshold Presentations of Anxious Face Stimuli in Adults with Autism Spectrum Disorders: Preliminary Insights

Current theoretical models of autism spectrum disorders (ASD) have proposed that impairments in the processing of social/emotional information may be linked to amygdala dysfunction. However, the extent to which amygdala functions are compromised in ASD has become a topic of debate in recent years. In a jittered functional magnetic resonance imaging study, sub-threshold presentations of anxious faces permitted an examination of amygdala recruitment in 12 high functioning adult males with ASD and 12 matched controls. We found heightened neural activation of the amygdala in both high functioning adults with ASD and matched controls. Neither the intensity nor the time-course of amygdala activation differed between the groups. However, the adults with ASD showed significantly lower levels of fusiform activation during the trials compared to controls. Our findings suggest that in ASD, the transmission of socially salient information along sub-cortical pathways is intact: and yet the signaling of this information to structures downstream may be impoverished, and the pathways that facilitate subsequent processing deficient

Asymmetric Switching in a Homodimeric ABC Transporter: A Simulation Study

ABC transporters are a large family of membrane proteins involved in a variety of cellular processes, including multidrug and tumor resistance and ion channel regulation. Advances in the structural and functional understanding of ABC transporters have revealed that hydrolysis at the two canonical nucleotide-binding sites (NBSs) is co-operative and non-simultaneous. A conserved core architecture of bacterial and eukaryotic ABC exporters has been established, as exemplified by the crystal structure of the homodimeric multidrug exporter Sav1866. Currently, it is unclear how sequential ATP hydrolysis arises in a symmetric homodimeric transporter, since it implies at least transient asymmetry at the NBSs. We show by molecular dynamics simulation that the initially symmetric structure of Sav1866 readily undergoes asymmetric transitions at its NBSs in a pre-hydrolytic nucleotide configuration. MgATP-binding residues and a network of charged residues at the dimer interface are shown to form a sequence of putative molecular switches that allow ATP hydrolysis only at one NBS. We extend our findings to eukaryotic ABC exporters which often consist of two non-identical half-transporters, frequently with degeneracy substitutions at one of their two NBSs. Interestingly, many residues involved in asymmetric conformational switching in Sav1866 are substituted in degenerate eukaryotic NBS. This finding strengthens recent suggestions that the interplay of a consensus and a degenerate NBS in eukaroytic ABC proteins pre-determines the sequence of hydrolysis at the two NBSs

Suicidality among adolescents engaging in nonsuicidal self-injury (NSSI) and firesetting: The role of psychosocial characteristics and reasons for living

Background: Co-occurrence of problem behaviors, particularly across internalizing and externalizing spectra, increases the risk of suicidality (i.e., suicidal ideation and attempt) among youth. Methods: We examined differences in psychosocial risk factors across levels of suicidality in a sample of 77 school-based adolescents engaging in both nonsuicidal self-injury (NSSI) and repeated firesetting. Participants completed questionnaires assessing engagement in problem behaviors, mental health difficulties, negative life events, poor coping, impulsivity, and suicidality. Results: Adolescents endorsing suicidal ideation reported greater psychological distress, physical and sexual abuse, and less problem solving/goal pursuit than those with no history of suicidality; adolescents who had attempted suicide reported more severe NSSI, higher rates of victimization and exposure to suicide, relative to those with suicidal ideation but no history of attempt. Additional analyses suggested the importance of coping beliefs in protecting against suicidality. Conclusions: Clinical implications and suggestions for future research relating to suicide prevention are discussed

Dopamine manipulations modulate paranoid social inferences in healthy people

Altered dopamine transmission is thought to influence the formation of persecutory delusions. However, despite extensive evidence from clinical studies there is little experimental evidence on how modulating the dopamine system changes social attributions related to paranoia, and the salience of beliefs more generally. Twenty seven healthy male participants received 150mg L-DOPA, 3 mg haloperidol, or placebo in a double-blind, randomised, placebo-controlled study, over three within-subject sessions. Participants completed a multi-round Dictator Game modified to measure social attributions, and a measure of belief salience spanning themes of politics, religion, science, morality, and the paranormal. We preregistered predictions that altering dopamine function would affect (i) attributions of harmful intent and (ii) salience of paranormal beliefs. As predicted, haloperidol reduced attributions of harmful intent across all conditions compared to placebo. L-DOPA reduced attributions of harmful intent in fair conditions compared to placebo. Unexpectedly, haloperidol increased attributions of self-interest about opponents’ decisions. There was no change in belief salience within any theme. These results could not be explained by scepticism or subjective mood. Our findings demonstrate the selective involvement of dopamine in social inferences related to paranoia in healthy individuals