Depression and Anxiety Associate With Adverse Cardiovascular Events via Neural, Autonomic, and Inflammatory Pathways.

Area of Science:

• Cardiology
• Psychiatry
• Neuroscience

Background:

• Depression is a known risk factor for major adverse cardiac events (MACE).
• The specific mechanisms linking depression, anxiety, and MACE, particularly the role of stress-related neural activity, are not fully understood.
• Anxiety and depression often co-occur and share underlying neurobiological pathways.

Purpose of the Study:

• To investigate if stress-related neural activity and autonomic-immune mechanisms mediate the association between depression, anxiety, and MACE.
• To examine the combined effect of depression and anxiety on MACE risk.
• To explore the shared pathophysiology between mental health conditions and cardiovascular outcomes.

Main Methods:

• Utilized data from the Mass General Brigham Biobank (2010-2020) with over 85,000 participants.
• Assessed stress-related neural activity using 18F-FDG PET/CT imaging (amygdala to prefrontal cortex activity ratio).
• Measured autonomic activity (heart rate variability) and systemic inflammation (CRP), and analyzed depression, anxiety, and MACE incidence.

Main Results:

• Depression was significantly associated with increased MACE risk (HR 1.24), with a stronger association for concurrent depression and anxiety (HR 1.35).
• Depression correlated with higher amygdala-to-cortex activity ratio, lower heart rate variability, and higher CRP levels.
• Mediation analyses confirmed that amygdala-to-cortex activity, heart rate variability, and CRP partially explained the link between depression and MACE.

Conclusions:

• Depression and anxiety independently increase MACE risk.
• Heightened stress-related neural activity and autonomic-immune dysregulation partially mediate this increased cardiovascular risk.
• The highest MACE risk is observed in individuals with both depression and anxiety, suggesting a common stress-related pathophysiology.