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

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.