Link between depression and cardiovascular disease finally explained: partly developed from the same gene module

Editorial Medicalfacts / Janine Budding April 26, 2024 – 5:30 PM

Array

Blood gene expression analysis reveals functional module of genes involved in both depression and cardiovascular disease

It has long been known that depression and cardiovascular disease are linked in some way, although the precise link has remained a mystery. Now researchers have identified a ‘gene module’ consisting of 256 functionally related, co-expressed genes, which are part of the developmental program of both diseases. These genes can now be used as biomarkers for both depression and cardiovascular disease, and could ultimately help find new drugs to tackle both.

Depression and CVD

Depression and cardiovascular disease (CVD) are serious public health concerns. Worldwide, approximately 280 million people have depression, while 620 million people have CVD. Since the 1990s it has been known that the two diseases are related in some way. For example, people with depression are at greater risk of CVD, while effective early treatment of depression reduces the risk of developing CVD later by half. Conversely, people with CVD often also have depression. For these reasons, the American Heart Association (AHA) recommends monitoring teens with depression for CVD.

What was not yet known is what causes this apparent relationship between the two diseases. Part of the answer likely lies in lifestyle factors that are common in patients with depression and that increase the risk of CVD, such as smoking, alcohol abuse, lack of exercise and poor diet. But it is also possible that the two diseases are related on a deeper level, through shared developmental pathways.

Gene module

Now scientists have shown that depression and CVD do indeed share part of their developmental program, with at least one functional ‘gene module’ in common. This result, published in Frontiers in Psychiatry, provides new markers for depression and CVD, and could ultimately help find drugs to tackle both diseases.

“We looked at the gene expression profile in the blood of people with depression and CVD and found 256 genes in a single gene module whose expression at higher or lower levels than average puts people at greater risk for both diseases,” said first author Dr. Binisha H Mishra, a postdoctoral researcher at the University of Tampere in Finland.

The authors define a gene module as a group of genes with similar expression patterns under different conditions and thus likely to be functionally related.

Young Finns study

Mishra and colleagues examined gene expression data in the blood of 899 women and men between 34 and 49 years old who were participants in the Young Finns study, one of the largest studies of cardiovascular risk factors from childhood to adulthood to date. The Young Finns study began in 1980 with a cohort of almost 4,000 children and adolescents, aged between three and 18 years old at the time, randomly selected from five cities in Finland. The health of these participants has since been monitored.

Finland has the highest estimated incidence of mental disorders in the EU, and ranks ninth globally for the prevalence of depression. In contrast, the country has a relatively low prevalence of CVD, ranking in the bottom 20% globally for this class of diseases.

In 2011, researchers from the Young Finns study tested participants for symptoms of depression with a proven questionnaire: the Beck Depression Inventory (BDI-II), whose score increases with more severe symptoms. They also tested them for risk of developing CVD via the AHA’s “ideal cardiovascular health” score, on a scale of zero (highest risk) to seven (lowest risk). Mishra et al further analyzed these data for the current study.

It’s all in the blood

Whole blood was also collected from each participant in 2011, and Mishra and colleagues analyzed these samples here using advanced gene expression methods.

They used advanced statistics to identify 22 different gene modules, only one of which was associated with both a high score for depressive symptoms and a low score for cardiovascular health.

“The top three genes from this gene module are known to be associated with neurodegenerative diseases, bipolar disorder and depression. Now we have shown that they are also associated with poor cardiovascular health,” Mishra said.

These genes are involved in biological processes such as inflammation that are involved in the pathogenesis of both depression and cardiovascular disease. This explains why both diseases often occur together.

Other genes in the shared module have been shown to be involved in brain diseases such as Alzheimer’s, Parkinson’s and Huntington’s.

“We can use the genes in this module as biomarkers for depression and cardiovascular disease. Ultimately, these biomarkers may facilitate the development of preventive strategies for both diseases,” Mishra said.

Source: Tampere University, Tampere, Finland