Trait anxiety is related to Nx4's efficacy on stress-induced changes in amygdala-centered resting state functional connectivity: a placebo-controlled cross-over trial in mildly to moderately stressed healthy volunteers

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. 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. 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. 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.