Responding to uncertain threat:A potential mediator for the effect of mindfulness on anxiety

Mindfulness-based interventions have gained extensive support for their application in the treatment of anxiety. However, their mechanisms remain largely unexplored. Excessive reactivity to uncertainty plays a central role in anxiety, and may represent a mechanism for the effect of mindfulness on anxiety, as mindfulness training fosters an open and accepting stance towards all aspects of experience. The present study sought to investigate both (i) self-reported intolerance of uncertainty (IU) as well as (ii) physiological and subjective responding to uncertain threat in a threat-of-shock paradigm, the NPU-threat test, as mediators for the relationship between mindfulness and anxiety in a cross-sectional study of healthy participants (N = 53). The results indicated that IU mediated the effect of mindfulness on some anxiety symptoms. In contrast, scores of physiological as well as subjective responses to uncertain threat from the NPU-threat test were largely unrelated to mindfulness, anxiety, or the IU self-report measure. The results provide initial evidence that reactions to uncertainty may play a role in the mindfulness-anxiety relationship and suggest that studies are needed to address how methodological variations of the NPU-threat test affect perceived levels of uncertainty and uncertainty-related anxiety

ENIGMA-anxiety working group : Rationale for and organization of large-scale neuroimaging studies of anxiety disorders

Altres ajuts: Anxiety Disorders Research Network European College of Neuropsychopharmacology; Claude Leon Postdoctoral Fellowship; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, 44541416-TRR58); EU7th Frame Work Marie Curie Actions International Staff Exchange Scheme grant 'European and South African Research Network in Anxiety Disorders' (EUSARNAD); Geestkracht programme of the Netherlands Organization for Health Research and Development (ZonMw, 10-000-1002); Intramural Research Training Award (IRTA) program within the National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, MH002781); National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, ZIA-MH-002782); SA Medical Research Council; U.S. National Institutes of Health grants (P01 AG026572, P01 AG055367, P41 EB015922, R01 AG060610, R56 AG058854, RF1 AG051710, U54 EB020403).Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA-Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA-Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA-Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders

Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the enigma-anxiety working group

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5–90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology

The effect of threat on novelty evoked amygdala responses.

A number of recent papers have suggested that the amygdala plays a role in the brain's novelty detection circuit. In a recent study, we showed that this role may be specific to certain classes of biologically-relevant stimuli, such as human faces. The purpose of the present experiment was to determine whether other biologically-relevant stimuli also evoke novelty specific amygdala responses. To test this idea, we presented novel and repeated images of snakes and flowers while measuring BOLD. Surprisingly, we found that novel images of snakes and flowers evoke more amygdala activity than repeated images of snakes and flowers. Our results further confirm the robustness of the novelty evoked amygdala responses, even when compared with effects more traditionally associated with the amygdala. In addition, our results suggest that threatening stimuli may prime the amygdala to respond to other types of stimuli as well

IAPS Normative Ratings.

<p>IAPS Normative Ratings.</p

Novel snakes and novel flowers drive BOLD activity in the amygdala and hippocampus.

<p>(<b>a,c</b>) Line graphs represent BOLD timecourse in the amygdala (<b>a</b>) and hippocampus (<b>c</b>). (<b>b,d</b>) Bar graphs represent the percent signal change in the amygdala (<b>b</b>) and hippocampus (<b>d</b>) during the last two seconds of the stimulus period. All data points represent mean±SEM. (NS = novel snake, RS = repeated snake, NF = novel flower, RF = repeated flower).</p