Yan Fan

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 registrationNCT02602275.

Background: The basic functional organization of the resting brain, assessed as resting-state functional connectivity (rsFC), can be affected by previous stress experience and it represents the basis on which subsequent stress experience develops. Notably, the rsFC between the amygdala and the cortical regions associated with emotion regulation and anxiety are affected during stress. The multicomponent drug Neurexan ^® (Nx4) has previously demonstrated a reduction in amygdala activation in an emotional face matching task and it ameliorated stress-related symptoms. We, thus, investigated the effect of Nx4 on rsFC of the amygdala before stress induction compared with baseline in mildly to moderately stressed participants. Methods: In a randomized, placebo-controlled, double-blind, crossover trial 39 participants received a single dose of placebo or Nx4. Resting-state functional magnetic resonance imaging scans were performed pre-dose and 40 to 60 min post-dose, before any stress induction. First, highly connected functional hubs were identified by global functional connectivity density (gFCD) analysis. Second, by using a seed-based approach, rsFC maps of the left centromedial amygdala (CeMA) were created. The effect of Nx4 on both was evaluated. Results: The medial prefrontal cortex was identified as a relevant functional hub affected by Nx4 in an explorative whole brain gFCD analysis. Using the seed-based approach, we then demonstrated that Nx4 significantly enhanced the negative connectivity between the left CeMA and two cortical regions: the dorsolateral and medial prefrontal cortices. Conclusions: In a resting-state condition, Nx4 reduced the prefrontal cortex gFCD and strengthened the functional coupling between the amygdala and the prefrontal cortex that is relevant for emotion regulation and the stress response. Further studies should elaborate whether this mechanism represents enhanced regulatory control of the amygdala at rest and, consequently, to a diminished susceptibility to stress. ClinicalTrials.gov ID: NCT02602275.

During the COVID-19 pandemic, many employees were asked to start working from home for an extended time. The current study investigated how well employees worked and felt in this novel situation by following n = 199 German employees—56% of them female, 24% with childcare duties—over the course of two working weeks in which they reported once daily on their well-being (PANAS-20, detachment) and motivation (work engagement, flow). Participants reported on organizational and personal resources (emotional exhaustion, emotion regulation, segmentation preference, role clarity, job control, social support). Importantly, they indicated how well their work-related basic needs, i.e., autonomy, competence, and relatedness, were met when working from home and how these needs had been met in the office. Multilevel models of growth showed that work engagement, flow, affect and detachment were on average positive and improving over the two weeks in study. Higher competence need satisfaction predicted better daily work engagement, flow, and affect. In a network model, we explored associations and dynamics between daily variables. Overall, the results suggest that people adapted well to the novel situation, with their motivation and well-being indicators showing adequate levels and increasing trajectories. Avenues for improving work from home are job control and social support.

Early life stress is an important factor in later psychopathology, including symptoms of posttraumatic stress disorder (PTSD), depression, and anxiety. The purpose of the present study was to investigate the effect of early life stress on psychiatric symptoms within a sample of Syrian refugees. In this model, the use of cognitive emotion regulation strategies was assessed as a potential mediator of the relationship between early life stress and current symptoms of PTSD, depression, and anxiety. Bootstrap analyses were generated to test the indirect effect of emotion regulation (Cognitive Emotion Regulation Questionnaire) on the relationship between early life stress (Childhood Trauma Questionnaire), PTSD (Harvard Trauma Questionnaire), depressive (PHQ-9) and anxiety (GAD-7) symptoms in eighty-nine Syrian refugees resided in Germany (n = 49) and Jordan (n = 40). The indirect effect of maladaptive strategies was significant between early life stress and psychopathology, whereas the mediation effect of adaptive strategies was not significant. The findings provide an evidence that emotional dysregulation is an underlying factor affecting psychological symptoms in refugees with adverse childhood experiences. These results suggest targeting cognitive emotion regulation in prospective prevention and treatment strategies.

Social stress contributes to major societal health burdens, such as anxiety disorders and nervousness. Nx4 has been found to modulate stress responses. We investigated whether dampening of such responses is associated with neuronal correlates in brain regions involved in stress and anxiety. In a randomized, placebo-controlled, double-blind, cross-over trial, 39 healthy males took a single dose (three tablets) of either placebo or Nx4, 40 to 60 minutes before an fMRI scan session. We here report on drug effects on amygdala responses during a face-matching task, which was performed during a complex test battery further including resting-state brain connectivity and a social stress experiment. The first of the Primary Outcomes, defined in a hierarchical order, concerned reduced amygdala effects after intake of verum compared to placebo. We found a statistically significant reduction in differential activations in the left amygdala for the contrast negative faces versus forms during verum versus placebo condition. Our results indicate that effects of Nx4 can be monitored in the brain. Previously noted effects on stress responses may thus be modulated by affective brain regions including the amygdala.

Background: Across psychopathologies, trauma-exposed individuals suffer from difficulties in inhibiting emotions and regulating attention. In trauma-exposed individuals without psychopathology, only subtle alterations of neural activity involved in regulating emotions have been reported. It remains unclear how these neural systems react to demanding environments, when acute (non-traumatic but ordinary) stress serves to perturbate the system. Moreover, associations with subthreshold clinical symptoms are poorly understood.Methods: The present fMRI study investigated response inhibition of emotional faces before and after psychosocial stress situations. Specifically, it compared 25 women (mean age 31.5 ± 9.7 years) who had suffered severe early life trauma but who did not have a history of or current psychiatric disorder, with 25 age- and education-matched trauma-naïve women.Results: Under stress, response inhibition related to fearful faces was reduced in both groups. Compared to controls, trauma-exposed women showed decreased left inferior frontal gyrus (IFG) activation under stress when inhibiting responses to fearful faces, while activation of the right anterior insula was slightly increased. Also, groups differed in brain–behaviour correlations. Whereas stress-induced false alarm rates on fearful stimuli negatively correlated with stress-induced IFG signal in controls, in trauma-exposed participants, they positively correlated with stress-induced insula activation.Conclusion: Neural facilitation of emotion inhibition during stress appears to be altered in trauma-exposed women, even without a history of or current psychopathology. Decreased activation of the IFG in concert with heightened bottom-up salience of fear related cues may increase vulnerability to stress-related diseases.

Major depressive disorder (MDD) is associated with abnormal functional interactions among large-scale brain networks. Here we report findings from a randomized, active-controlled trial examining whether mindfulness-based therapy can regulate specific patterns of resting-state functional connectivity in clinically depressed patients. We show that a brief, clinically effective mindfulness intervention functionally decouples top-down control regions from brain areas implicated in sensory, affective, and attentional processing. While previous work has demonstrated the clinical impact of mindfulness training, the present findings shed light on the precise neural targets, providing new insight into the specificity of this therapeutic approach.