A young Asian boy holding a red heart in both hands to symbolize heart shape and links with congenital heart defect (CHD)
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Coronary artery disease and major depression may be genetically interconnected via inflammatory pathways, according to researchers at the Vanderbilt University Medical Center (VUMC) and the Massachusetts General Hospital (MGH). They used transcriptome-wide association scans to map single nucleotide polymorphisms involved in regulating the expression of genes associated with both CAD and depression.

Their study suggests that drugs prescribed for coronary artery disease and depression, when used in combination, could reduce inflammation and prevent the development of cardiomyopathy, or damage to heart muscle.

“This work suggests that chronic low-level inflammation may be a significant contributor to both depression and cardiovascular disease,” said Lea Davis, PhD, the paper’s corresponding author is Lea Davis, PhD, and associate professor of Medicine in the Division of Genetic Medicine and Vanderbilt Genetics Institute.

This team’s report was published April 5 in Nature Mental Health. Kritika Singh, PhD, is the paper’s first author. He is a former graduate student in the Davis lab who is now a postdoctoral Innovation Fellow at Novartis in Cambridge, Massachusetts.

The connection between depression and other serious health conditions is well known. As many as 44% of patients with Coronary artery disease (CAD), the most common form of cardiovascular disease, also have a diagnosis of major depression. Yet the biological relationship between the two conditions remains poorly understood.

Since changes in the levels of inflammatory markers have been observed in both conditions there may be a common biological pathway linking neuroinflammation in depression with atherosclerotic inflammation in CAD.

In the current study, the researchers mapped known variants to genes, then identified genes, followed by pathways, associated with both depression and CAD. They investigated the phenotypic consequences of the shared pathways in an electronic health record (EHR)-based setting. They identified 185 genes significantly associated with both depression and CAD, which were “enriched” for biological roles in inflammation and cardiomyopathy. This suggests that predisposition to both depression and CAD, which the researchers called (major) depressive CAD, or (m)dCAD, may further predispose individuals to cardiomyopathy.

However, when the researchers scanned large electronic health record databases at VUMC, MGH, and the National Institutes of Health’s All of Us Research Program, they found the actual incidence of cardiomyopathy in patients with the enriched genes for (m)dCAD was lower than in patients with CAD alone.

One possible explanation is that medications prescribed for CAD and depression, such as statins and antidepressants, may prevent development of cardiomyopathy by reducing inflammation, the researchers concluded.

They write, “We observed an increased rate of prevalent cardiomyopathy cases in individuals with comorbid depression—CAD compared with those with CAD alone in three large EHR datasets. The results of our study implicate genetically regulated inflammatory mechanisms in depression—CAD. Our results also raise the hypothesis that depression-associated CAD may be enriched for cardiomyopathy.”

“More research is needed to investigate optimal treatment mechanisms,” Davis added, “but at a minimum this work suggests that patient heart and brain health should be considered together when developing management plans to treat depression or cardiovascular disease.”

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