# Pathophysiological mechanisms underlying the link between major depressive disorder and atherosclerotic cardiovascular disease

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- Page title: Pathophysiological mechanisms underlying the link between major depressive disorder and atherosclerotic cardiovascular disease | WCP 2026 Summary

> Immunometabolic dysregulation plays a role in the co-occurrence of major depressive disorder and atherosclerotic cardiovascular disease, while symptom-based su…

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# Pathophysiological mechanisms underlying the link between major depressive disorder and atherosclerotic cardiovascular disease

Pathophysiological mechanisms underlying the link between major depressive disorder and atherosclerotic cardiovascular disease

Sunan: Jacob Bergstedt

Ülke: Sweden

Oturum: 4340 - DECIPHERING THE HEART-MIND CONNECTION: LEVERAGING NORDIC GENEALOGY AND GLOBAL COHORTS TO MAP PSYCHIATRIC AND CARDIOMETABOLIC COMORBIDITY

Tarih: Sat, 26.09.2026, 09:15 - 09:15

Salon: Hall A7

Immunometabolic dysregulation plays a role in the co-occurrence of major depressive disorder and atherosclerotic cardiovascular disease, while symptom-based subtyping captures some of the cardiovascular heterogeneity in depression.

The study investigated whether the co-occurrence of atherosclerotic cardiovascular disease (ASCVD), which contributes to reduced life expectancy in individuals with major depressive disorder (MDD), reflects a shared pathophysiology and which pathways are involved. Swedish national registry data were integrated with genomic analyses of circulating metabolites and proteins and within-pair analyses of metabolites measured in 14,500 twins. Among 2,619,213 individuals, clinically diagnosed MDD was associated with incident ischemic heart disease and cerebrovascular disease (hazard ratios of 1.73 and 1.93, respectively). Metabolite analyses identified an immunometabolic signature characterized by triglyceride-rich lipoproteins, increased fatty acid saturation, and inflammation; low-density lipoprotein cholesterol was not part of this signature. Genetic analyses at the protein level highlighted fibroblast growth factor 21, hepatocyte growth factor, and carboxylesterase 1, proteins involved in endothelial function and atherosclerosis; conditioning on these proteins reduced the genetic correlation between MDD and ischemic heart disease by 50%. To address MDD heterogeneity, genome-wide association studies were conducted for MDD with atypical energy-related symptoms (AERS+; increased weight and appetite, hypersomnia), MDD with the opposite symptom pattern (AERS), and a latent factor reflecting shared MDD–ASCVD susceptibility; genetic correlations with triglyceride-rich lipoproteins, glycoprotein acetyls, and C-reactive protein increased progressively from AERS through MDD and AERS+ to shared susceptibility (from 0.08 to 0.35 for triglycerides and from 0.04 to 0.32 for C-reactive protein), whereas correlations with lipoprotein particle size decreased. The findings point to opportunities for more targeted cardiovascular prevention.

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APA 7: Bergstedt, J., et al. (2026, September 26). Pathophysiological mechanisms underlying the link between major depressive disorder and atherosclerotic cardiovascular disease [Oral presentation]. 26th WPA World Congress of Psychiatry (WCP 2026), Stockholm, Sweden.

Vancouver: Bergstedt J, et al. Pathophysiological mechanisms underlying the link between major depressive disorder and atherosclerotic cardiovascular disease [oral presentation]. 26th WPA World Congress of Psychiatry (WCP 2026); 2026 Sep 23-26; Stockholm, Sweden.

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