Neural mechanisms of mindfulness: reduced neural reactivity to social-evaluative threat accounts for mindfulness intervention effects on inflammatory gene expression.

Mindful awareness redirects attention toward the present moment, which may reduce threat-related neural activity and downstream inflammation in response to stress. Social-evaluative threat, where the self is negatively judged by others, is a stressor with potent inflammatory consequences. As part of a randomized controlled trial (NCT05304052), the current study tested whether a mindfulness intervention reduced neural reactivity to social-evaluative threat and reduced downstream pro-inflammatory signaling. Healthy young adults were randomly assigned to a waitlist control group (n = 23) or a 6-week mindfulness intervention (Mindful Awareness Practices; MAPs; n = 26) that has previously been shown to reduce stress and inflammation. Pre- and post-intervention, we collected blood samples and BOLD neuroimaging data during a social-evaluative threat task (modified Montreal Imaging Stress Task; MIST), focusing on activity in three threat-related neural regions: amygdala, dorsal anterior cingulate cortex, and anterior insula. Leukocyte genome-wide RNA profiles were analyzed using promoter-based bioinformatic analyses to infer NF-κB transcription factor activity, a canonical pro-inflammatory signaling pathway. Relative to waitlist control, the MAPs intervention led to reductions in neural threat reactivity. MAPs also reduced NF-κB activity relative to the control condition, and this effect was no longer significant when controlling for changes in neural threat reactivity. Results suggest that reductions in threat-related neural activity may contribute to the beneficial effects of mindfulness on inflammation.