Scientists Finally Explain Puzzling Link Between Depression and Cardiovascular Disease

Depression and cardiovascular disease (CVD) are intricately linked, as both share certain lifestyle risks and genetic pathways, including a gene module identified in a Finnish study that correlates with both conditions. This discovery provides new biomarkers for both diseases and may aid in the development of treatments targeting them simultaneously.

Gene expression analysis of blood identifies a functional group of genes linked to both depression and cardiovascular disease.

Depression and cardiovascular disease (CVD) pose significant challenges to global health. An estimated 280 million individuals globally suffer from depression, and around 620 million are affected by CVD. Research since the 1990s has highlighted a connection between these two conditions. For instance, individuals with depression are at a higher risk of developing CVD, and early and effective treatment of depression can reduce the risk of CVD by 50%. Similarly, those diagnosed with CVD often experience depression. For these reasons, the American Heart Association (AHA) advises to monitor teenagers with depression for CVD.

What wasn’t yet known is what causes this apparent relatedness between the two diseases. Part of the answer probably lies in lifestyle factors common in patients with depression and which increase the risk of CVD, such as smoking, alcohol abuse, lack of exercise, and a poor diet. But it’s also possible that both diseases might be related at a deeper level, through shared developmental pathways.

Now, scientists have shown that depression and CVD do indeed share part of their developmental programs, having 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 to find drugs to target both diseases.

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

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

Young Finns study

Mishra and colleagues studied 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 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, then between three and 18 years old, randomly selected from five cities in Finland. The health of these participants has been followed ever since.

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

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

It’s all in the blood

In 2011, whole blood had also been taken from each participant, and Mishra and colleagues here analyzed these samples with state-of-the-art gene expression methods.

They used advanced statistics to identify 22 distinct gene modules, of which just one 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 associated with poor cardiovascular health as well,” said Mishra.

These genes are involved in biological processes such as inflammation that are involved in pathogenesis of both depression and cardiovascular disease. This helps to explain 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 disease.

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

Reference: “Identification of gene networks jointly associated with depressive symptoms and cardiovascular health metrics using whole blood transcriptome in the Young Finns Study” by Binisha H. Mishra, Emma Raitoharju, Nina Mononen, Aino Saarinen, Jorma Viikari, Markus Juonala, Nina Hutri-Kähönen, Mika Kähönen, Olli T. Raitakari, Terho Lehtimäki and Pashupati P. Mishra, 12 February 2024, Frontiers in Psychiatry.
DOI: 10.3389/fpsyt.2024.1345159

The Young Finns Study has been financially supported by the Academy of Finland: grants 356405, 322098, 286284, 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117797 (Gendi), and 141071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (grant 755320 for TAXINOMISIS and grant 848146 for To Aition); European Research Council (grant 742927 for MULTIEPIGEN project); Tampere University Hospital Supporting Foundation; Finnish Society of Clinical Chemistry; the Cancer Foundation Finland; pBETTER4U_EU (Preventing obesity through Biologically and bEhaviorally Tailored inTERventions for you; project number: 101080117); and the Jane and Aatos Erkko Foundation. Pashupati P. Mishra was supported by the Academy of Finland (Grant number: 349708) and Emma Raitoharju (grants: 330809, 338395)

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