Summary: A new study uncovered a genetic connection between coronary artery disease, major depression, and an increased risk for cardiomyopathy, mediated through inflammatory pathways. The study highlights that medications used for treating coronary artery disease and depression could synergistically reduce inflammation, potentially preventing cardiomyopathy.
By analyzing genetic data and electronic health records, the researchers identified 185 genes associated with both depression and coronary artery disease, suggesting a shared biological pathway involving inflammation. This discovery emphasizes the importance of integrated treatment plans that address both cardiovascular and mental health, paving the way for future research on optimal treatment strategies.
Key Facts:
- Genetic analysis revealed 185 genes linked to both major depression and coronary artery disease, indicating a shared inflammatory pathway that may lead to cardiomyopathy.
- Medications for coronary artery disease and depression may jointly reduce inflammation, suggesting a potential preventative approach to cardiomyopathy.
- The study’s findings advocate for a holistic treatment approach, considering both heart and brain health in managing depression and cardiovascular disease.
Source: Vanderbilt University
Coronary artery disease and major depression may be genetically linked via inflammatory pathways to an increased risk for cardiomyopathy, a degenerative heart muscle disease, researchers at Vanderbilt University Medical Center and Massachusetts General Hospital have found.
Their report, published April 5 in the journal Nature Mental Health, suggests that drugs prescribed for coronary artery disease and depression, when used in combination, potentially may reduce inflammation and prevent the development of cardiomyopathy.
“This work suggests that chronic low-level inflammation may be a significant contributor to both depression and cardiovascular disease,” said the paper’s corresponding author, Lea Davis, PhD, associate professor of Medicine in the Division of Genetic Medicine and Vanderbilt Genetics Institute.
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.
A possible connection is inflammation. Changes in the levels of inflammatory markers have been observed in both conditions, suggesting that there may be a common biological pathway linking neuroinflammation in depression with atherosclerotic inflammation in CAD.
In the current study, the researchers used a technique called transcriptome-wide association scans to map single nucleotide polymorphisms (genetic variations) involved in regulating the expression of genes associated with both CAD and depression.
The technique identified 185 genes that were significantly associated with both depression and CAD, and 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, Mass General, 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.
“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.”
Kritika Singh, PhD, the paper’s first author, is a former graduate student in the Davis lab who is now a postdoctoral Innovation Fellow at Novartis in Cambridge, Massachusetts.
Other VUMC co-authors are Tyne Miller-Fleming, PhD, Peter Straub, MS, Nancy Cox, PhD, founding director of the Vanderbilt Genetics Institute, and institute members Quinn Wells, MD, PharmD, MSCI, associate professor of Medicine in the Division of the Cardiovascular Medicine, and Emily Hodges, PhD, assistant professor of Biochemistry.
Funding: The research was supported by National Institutes of Health grants R56MH120736, R01H118233, 1F31MH124306, and 1R01HL140074, and an American Heart Association Fellowship.
About this depression, genetics, and inflammation research news
Author: Craig Boerner
Source: Vanderbilt University
Contact: Craig Boerner – Vanderbilt University
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“Genes associated with depression and coronary artery disease are enriched for cardiomyopathy and inflammatory phenotypes” by Lea Davis et al. Nature Mental Health
Abstract
Genes associated with depression and coronary artery disease are enriched for cardiomyopathy and inflammatory phenotypes
Depression and coronary artery disease (CAD) are highly comorbid conditions. Approximately 40% of individuals who have one diagnosis will also develop the other within their lifetime. Despite the high prevalence of the comorbidity, the specific genes and pathways remain unknown.
Here, by mapping known variants to genes, we identified genes, followed by pathways, that are associated with both depression and CAD.
Next, we investigated the phenotypic consequences of the shared pathways in an electronic health record (EHR)-based setting.
We identified 185 genes that were significantly associated with both depression and CAD and were enriched for inflammatory and cardiomyopathy phenotypes.
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.
