Stress-Related Brain Activity Partly Explains the Link between Depression, Anxiety, and Cardiac Events

Depression and anxiety were each associated with a higher risk of major adverse cardiac events, with the greatest risk observed when both conditions co-occurred, and these associations were partly mediated by heightened stress-related neural activity and downstream autonomic and inflammatory dysregulation. In more than 85,000 participants from the Mass General Brigham Biobank (2010–2020) followed for a median of 3.4 years, depression increased the risk of major adverse cardiac events (hazard ratio, 1.24), an effect that was stronger for individuals with concurrent anxiety and depression (hazard ratio, 1.35) and remained significant after extensive adjustment for confounders. In subgroups with imaging and biomarker data, depression and anxiety were linked to higher amygdala-to-prefrontal cortex activity, reduced heart rate variability, and elevated C-reactive protein levels, all markers of stress-related autonomic and immune activation. Mediation analyses confirmed that these neural and physiological pathways partially explained the relationship between depression, anxiety and cardiac risk, highlighting shared stress-related mechanisms. Source: https://www.ahajournals.org/