Chronic Stress Is Associated with Reduced Mindful Acceptance Skills but Not with Mindful Attention Monitoring: A Cross-Sectional Study.

Mindfulness-based interventions (MBIs) are effective in reducing chronic stress, but their therapeutic mechanisms are unclear. One possibility is that MBIs act by re-training attention monitoring and acceptance skills that have been impaired by chronic stress exposure. However, little research has investigated the association between chronic stress, monitoring, and acceptance. In this cross-sectional study we hypothesised observing correlations between stress, and (impaired) monitoring and acceptance. Moreover, we exploratively compared the magnitude of the correlations between chronic stress and four acceptance measures. Finally, we explored whether the association between stress and monitoring is moderated by acceptance. Eighty-five adults participated in the study and completed self-reported chronic stress and acceptance questionnaires and a mindful attention behavioural task. The results revealed that chronic stress was associated with reduced acceptance (all ps < 0.01) but not with monitoring. Exploratory analyses revealed no differences in the magnitude of the correlations between stress and each acceptance measure, except for the combined facets of mindfulness acceptance subscales and nonreactivity subscale (p = 0.023). Further analyses revealed a significant negative association between stress and the interaction between acceptance and the target detection component of monitoring (p = 0.044). Surprisingly, these results show that stress is associated with reduced monitoring at higher levels of acceptance. Theory-driven intervention studies are warranted to complement our results.

The effects of psilocybin on cognitive and emotional functions in healthy participants: Results from a phase 1, randomised, placebo-controlled trial involving simultaneous psilocybin administration and preparation.

BACKGROUND: Psilocybin, a psychoactive serotonin receptor partial agonist, has been reported to acutely reduce clinical symptoms of depressive disorders. Psilocybin's effects on cognitive function have not been widely or systematically studied. AIM: The aim of this study was to explore the safety of simultaneous administration of psilocybin to healthy participants in the largest randomised controlled trial of psilocybin to date. Primary and secondary endpoints assessed the short- and longer-term change in cognitive functioning, as assessed by a Cambridge Neuropsychological Test Automated Battery (CANTAB) Panel, and emotional processing scales. Safety was assessed via endpoints which included cognitive function, assessed by CANTAB global composite score, and treatment-emergent adverse event (TEAE) monitoring. METHODS: In this phase 1, randomised, double-blind, placebo-controlled study, healthy participants (n = 89; mean age 36.1 years; 41 females, 48 males) were randomised to receive a single oral dose of 10 or 25 mg psilocybin, or placebo, administered simultaneously to up to six participants, with one-to-one psychological support - each participant having an assigned, dedicated therapist available throughout the session. RESULTS: In total, 511 TEAEs were reported, with a median duration of 1.0 day; 67% of all TEAEs started and resolved on the day of administration. There were no serious TEAEs, and none led to study withdrawal. There were no clinically relevant between-group differences in CANTAB global composite score, CANTAB cognitive domain scores, or emotional processing scale scores. CONCLUSIONS: These results indicate that 10 mg and 25 mg doses of psilocybin were generally well tolerated when given to up to six participants simultaneously and did not have any detrimental short- or long-term effects on cognitive functioning or emotional processing. CLINICAL TRIAL REGISTRATION: EudraCT (https://www.clinicaltrialsregister.eu/) number: 2018-000978-30.

Neural correlates of working memory function in euthymic people with bipolar disorder compared to healthy controls: A systematic review and meta-analysis.

BACKGROUND: Bipolar disorders (BD) are serious mental health disorders that impacts on cognitive and social functioning. We aimed to systematically review and conduct a meta-analysis of fMRI correlates of working memory in euthymic people with BD compared to healthy participants. METHOD: Web of Science, Embase and PubMed databases were systematically searched to identify studies which examined the fMRI correlates of working memory function in euthymic people with BD and healthy participants. Relevant demographic, behavioral and functional MRI (fMRI) data was qualitatively and quantitatively assessed, and the quality of the included studies evaluated. Comparable studies which used the same working memory task were included in a meta-analysis using Seed-Based D Mapping software (SDM). RESULTS: Twenty-four studies were included in this systematic review. Consistent brain fMRI activity differences were found in key brain areas of the working memory network in euthymic people with BD compared to healthy participants including the ventromedial and dorsolateral prefrontal cortices. Cognitive performance was not significantly different between the two groups. Six studies were suitable to be included in the meta-analysis. There was no significant overlap in areas of brain activation after family-wise correction for multiple comparisons. LIMITATIONS: Heterogeneity of task paradigms, small sample sizes and inherent difficulty in the interpretation of functional brain activity due to variations between studies were all limitations. CONCLUSION: The differences in working memory related fMRI activity identified by this study between people with BD and healthy participants are consistent with existing literature reporting impaired working memory performance in BD. This was not accompanied by significant differences in cognitive performance in the reviewed studies, likely due to small sample sizes. Further studies are needed to investigate the relationship between differential brain activity and working memory performance in people with BD.

Inflammatory biomarkers and cognitive functioning in individuals with euthymic bipolar disorder: exploratory study.

BACKGROUND: Neurobiological research frequently implicates inflammatory and neurogenic components with core aspects of bipolar disorder. Even in periods of symptom remission (euthymia), individuals with bipolar disorder experience cognitive impairments, which are increasingly being proposed as an outcome for interventions; identifying biomarkers associated with cognitive impairment in people with bipolar disorder could advance progress in this therapeutic field through identifying biological treatment targets. AIMS: We aimed to identify proteomic biomarker correlates of cognitive impairment in individuals with euthymic bipolar disorder. METHOD: Forty-four adults with a bipolar disorder diagnosis in euthymia underwent a battery of cognitive assessments and provided blood for biomarkers. We examined a comprehensive panel of inflammatory and trophic proteins as putative cross-sectional predictors of cognition, conceptualised according to recommended definitions of clinically significant cognitive impairment (binary construct) and global cognitive performance (continuous measure). RESULTS: A total of 48% of the sample met the criteria for cognitive impairment. Adjusting for potentially important covariates, regression analyses identified lower levels of three proteins as significantly and independently associated with cognitive deficits, according to both binary and continuous definitions (interleukin-7, vascular endothelial growth factor C and placental growth factor), and one positively correlated with (continuous) global cognitive performance (basic fibroblast growth factor). CONCLUSIONS: This study identifies four candidate markers of cognitive impairment in bipolar disorder, none of which have been previously compared with cognitive function in participants with bipolar disorder. Pending replication in larger samples and support from longitudinal studies, these markers could have implications for treating cognitive dysfunction in this patient population.

The role of threat level and intolerance of uncertainty in extinction.

Recent evidence suggests that individual differences in intolerance of uncertainty (IUS) are associated with disrupted threat extinction. However, it is unknown what maintains the learned threat association in high IUS individuals: is it the experienced uncertainty during extinction or the combination of experienced uncertainty with potential threat during extinction? Here we addressed this question by running two independent experiments with uncertain auditory stimuli that varied in threat level (Experiment 1, aversive human scream (n = 30); Experiment 2, neutral tone (n = 47) and mildly aversive tone (n = 49)). During the experiments, we recorded skin conductance responses and subjective ratings to the learned cues during acquisition and extinction. In experiment 1, high IUS was associated with heightened skin conductance responding to the learned threat vs. safe cue during extinction. In experiment 2, high IUS was associated only with larger skin conductance responding to the learned cues with more threatening properties during extinction i.e. mildly aversive tone. These findings suggest that uncertainty in combination with threat, even when mild, disrupts extinction in high IUS individuals. Such findings help us understand the link between IUS and threat extinction, and its relevance to anxiety disorder pathology.