Metacognitive awareness, insight into one’s abilities, is thought to be disrupted in depression and posttraumatic stress disorder (PTSD), with more negative metacognitive biases and reduced awareness, respectively. However, studies have rarely examined global aspects of metacognitive awareness in depression and PTSD, instead using task-specific measures. In 467 trauma-exposed post-9/11 veterans, we administered assessments of PTSD and depression, self-report and objective measures of cognitive functioning (neuropsychological battery of memory, attention, and executive function measures), and self-report and objective measures of general health (index of five cardiometabolic factors). We used self-report/objective correlations to measure metacognitive sensitivity and 'self-report minus objective' scores to measure bias. We also examined associations between changes in metacognitive awareness and changes in PTSD and depression over time. Metacognitive sensitivity was comparable between individuals with and without PTSD and depression. However, metacognitive bias was significantly more negative in those with greater depressive symptoms (i.e., underconfidence) across cognition and health, independent of PTSD symptoms. Notably, metacognitive bias changes covaried with depressive and PTSD symptom changes two years later. This shows that, in trauma-exposed veterans, negative metacognitive biases are specifically related to depressive symptoms and these biases may be relatively domain general. Further, our longitudinal results suggest that, rather than being a stable trait, metacognitive biases change with PTSD/depressive symptoms over time.
Background
The multicomponent drug Neurexan (Nx4) was shown to reduce the neural stress network activation. We now investigated its effects on stress-induced resting state functional connectivity (RSFC) in dependence of trait anxiety (TA), an acknowledged vulnerability factor for stress-induced psychopathologies.
Methods
Nx4 was tested in a randomized placebo-controlled crossover trial. Resting state fMRI scans were performed before and after a psychosocial stress task and exploratively analyzed for amygdala centered RSFC. Effects of Nx4 on stress-induced RSFC changes were evaluated and correlated to TA levels. A subgroup analysis based on TA scores was performed.
Results
Multiple linear regression analysis revealed a significant correlation between TA and Nx4 effect on stress-induced RSFC changes between right amygdala and pregenual anterior cingulate cortex (pgACC) and ventro-medial prefrontal cortex (vmPFC). For participants with above average TA, a significant amelioration of the stress-induced RSFC changes was observed.
Conclusions
The data add evidence to the hypothesis that Nx4’s clinical efficacy is based on a dampened activation of the neural stress network, with a greater neural response in subjects with anxious personality traits. Further studies assessing clinically relevant outcome measures in parallel to fMRI are encouraged to evaluate the real-world benefit of Nx4.
Trial registration NCT02602275.
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