From Brain Structure to Stress Response: COVID-Specific Anxiety Links Pre-Pandemic Gray Matter Volume to Changes in Life Satisfaction

The COVID-19 pandemic severely threatened mental well-being, potentially impacting individual life satisfaction (LS); thus, this study sought to identify pre-pandemic brain structural markers associated with subsequent LS changes and explore the role of COVID-specific anxiety in this relationship. We utilized structural magnetic resonance imaging (MRI) and behavioral data (including the LS scale) collected before the pandemic (T1) from 115 general university students, followed up 1 year after the outbreak (T2) for LS and COVID-anxiety measures. Employing whole-brain voxel-based morphometry (VBM) and confirmatory prediction analyses, we identified brain regions where pre-pandemic gray matter volume (GMV) correlated with subsequent LS changes (ΔLS from T1 to T2), followed by mediation analysis to assess the indirect effect of COVID-anxiety. While group-level ΔLS was stable, individual variability showed a significant negative correlation with pre-pandemic GMV in the pregenual anterior cingulate cortex (pgACC) and left superior temporal gyrus (STG), and a positive correlation with GMV in right precuneus. Furthermore, COVID-anxiety correlated with ΔLS, and mediation analysis revealed a significant negative indirect effect of COVID-anxiety on the link between pgACC GMV and ΔLS, such that greater pre-pandemic pgACC GMV was associated with higher COVID-specific anxiety, which in turn was associated with a decrease in LS. This mediation effect was partial, as the direct path from pgACC GMV to ΔLS remained significant. Crucially, these results were independent of socioeconomic status, stressful life events, and general mental health. Overall, our study indicates that pre-pandemic brain structure can prospectively predict individual LS changes during the pandemic, and this relationship was mediated by COVID-specific anxiety. These findings shed light on the neuroanatomical basis of LS and could have implications for targeted interventions during public health crises and similar challenges.