Depression, MACE Link Mediated by Stress-Related Neural Activity

TUESDAY, Dec. 23, 2025 (HealthDay News) — The association between depression and anxiety and major adverse cardiac events (MACE) is partly mediated by increased stress-related neural activity, according to a study published online Dec. 17 in Circulation: Cardiovascular Imaging.

Shady Abohashem, M.D., M.P.H., from Massachusetts General Hospital in Boston, and colleagues obtained data from participants enrolled in the Mass General Brigham Biobank to examine whether the relationship between depression, anxiety, and their cooccurrence with MACE is mediated by stress-related neural activity and related autonomic-immune mechanisms. To assess stress-related neural activity, a subset of participants underwent ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography imaging.

Over a median 3.4 years of follow-up, 3,078 (3.6 percent) of 85,551 participants developed MACE. The researchers found that depression was associated with higher MACE risk (hazard ratio, 1.24) and stronger associations were seen for concurrent anxiety plus depression (hazard ratio, 1.35); after adjustment for demographics, lifestyle, cardiovascular, and socioeconomic factors, the associations remained significant. Depression was linked to higher amygdala-to-cortex activity ratio, lower heart rate variability, and higher C-reactive protein (CRP) in subsamples with available imaging or biomarkers. Indirect effects were seen for amygdala-to-cortex activity ratio, heart rate variability, and CRP on the depression-MACE relationship in mediation analyses. For anxiety or concurrent anxiety plus depression, similar associations were observed.

“Together, these changes seem to form a biological chain linking emotional stress to cardiovascular risk,” Abohashem said in a statement. “When the brain”s stress circuits are overactive, they can chronically trigger the body”s “fight or flight” system, leading to increased heart rate, blood pressure, and chronic inflammation. Over time, these changes can damage blood vessels and accelerate heart disease.”

Two authors disclosed ties to industry.

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