Link between depression and cardiovascular diseases due to epigenomics and proteomics: Focus on energy metabolism

doi:10.1016/j.pnpbp.2018.09.004

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Volume 89, 8 March 2019, Pages 146-157

https://doi.org/10.1016/j.pnpbp.2018.09.004 Get rights and content

Highlights

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Major depression and cardiovascular diseases share several pathophysiological pathways.
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These include lifestyle factors, stress system activation, immune dysregulation, epigenomic and metabolomics alterations.
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Both disorders share genes involved in energy metabolism, stress system, circadian rhythm, inflammation, neurotransmission.
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Central metabolic pathways for ATP production are disturbed in major depression and cardiovascular disease.
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This points to the role of mitochondrial dysfunction and dysfunction of glucose transporter proteins.
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These results are promising factors to stimulate further research in energy metabolism dysfunction in both disorders.

Absract

Major depression is the most common mental disorder and a leading cause of years lived with disability. In addition to the burden attributed to depressive symptoms and reduced daily life functioning, people with major depression are at increased risk of premature mortality, particularly due to cardiovascular diseases. Several studies point to a bi-directional relation between major depression and cardiovascular diseases, thereby indicating that both diseases may share common pathophysiological pathways. These include lifestyle factors (e.g. physical activity, smoking behavior), dysfunctions of endocrine systems (e.g. hypothalamus-pituitary adrenal axis), and a dysbalance of pro- and anti-inflammatory factors. Furthermore, recent research point to the role of epigenomic and proteomic factors, that are reviewed here with a particular focus on the mitochondrial energy metabolism.

Introduction

Depression is the most common mental disorder and one of the leading cause of disability worldwide, affecting >300 million people (DALYs G, Collaborators H, 2017). Major depressive disorder (MDD) is characterized by sadness or anhedonia and a wide array of symptoms including depressed mood, loss of interest, appetite, and enjoyment, reduced energy, hopelessness, sleep disturbances, and suicidal ideation. Moreover, there is a well-known bidirectional relationship between MDD and cardiovascular diseases (CVD) including coronary heart disease, atherosclerosis, hypertension and stroke (Colton and Manderscheid, 2006; Dhar and Barton, 2016; Davidson and Korin, 2010).

CVD is the leading cause of mortality worldwide (Collaborators GBDM, 2017). Depression can multiply the risk of developing cardiovascular disease 1,5-fold in average (Lippi et al., 2009), so that WHO and the American Heart Association consider depression as a major risk factor for coronary heart disease, similar to hyperlipidemia, diabetes, hypertension, and smoking (Lichtman et al., 2014; Chaddha et al., 2016). On the other hand, cardiovascular diseases enhance the risk for depression - the prevalence of depression in patients with cardiovascular disease is threefold higher than in the general population (Lippi et al., 2009; Chaddha et al., 2016). More than every third patient with coronary artery disease, unstable angina, or myocardial infarction suffer from clinically significant depressive symptoms (Huffman et al., 2013). Moreover, a meta-analyses of 25 years of research showed that depression is an independent risk factor of a worse outcome after a cardiovascular event (Meijer et al., 2011). In conclusion, both disorders place a heavy burden on society and health system and also a profound impact on the quality of life of afflicted people.

The purpose of this review is to highlight the association between CVD and MDD due to epigenetic modulations and alterations in gene expressions or in other words due to epigenomics and proteomics with a focus on energy metabolisms. Better understanding of this relationship may provide new insights and innovative ways for the treatment of comorbid depression und cardiovascular diseases.

Section snippets

Methods

A literature search was done in PubMed, and search results were limited to English language papers published between January 2000 and January 2018. The searched MeSH terms were (depression AND/OR cardiovascular diseases) AND epigenetic OR DNA methylation OR microRNA OR long non-coding RNA OR proteomic) along with various combinations of the following terms: MDD, depressive, atherosclerosis, heart failure, infarction, coronary syndrome, thrombosis, biomarker, histone or DNA modification. Next,

Conclusion

In order to create a new research concept for defining links between MDD and CV which are of future therapeutic use we propose the energetic metabolism of mitochondria. The results we review here from epigenetic and proteomic alterations in patients with MDD or CVD together with our results from the regulation of GLUT1-transporter gene in the brain are promising factors to stimulate further research in energy metabolism dysfunction. We hope to discover some more links between CVD and MDD

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¹: Both first authors made equal contribution to the manuscript.

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Link between depression and cardiovascular diseases due to epigenomics and proteomics: Focus on energy metabolism

Highlights

Absract

Introduction

Section snippets

Methods

Conclusion

J. Thorac. Cardiovasc. Surg.

Gene

Prog. Neuro-Psychopharmacol. Biol. Psychiatry

Eur. Neuropsychopharmacol.

J. Psychiatr. Res.

Cell

Trends Genet.

Appetite

Psychoneuroendocrinology

J. Affect. Disord.

Neurobiol. Dis.

Am. J. Med.

J. Clin. Neurosci.

FEBS Lett.

J. Am. Coll. Cardiol.

J. Am. Coll. Cardiol.

Neurosci. Biobehav. Rev.

Prog. Mol. Biol. Transl. Sci.

Biol. Psychiatry

J. Am. Coll. Cardiol.

Biol. Psychiatry

Psychiatry Res.

Metabolism

Prog. Neuro-Psychopharmacol. Biol. Psychiatry

J. Affect. Disord.

J. Psychiatr. Res.

Mitochondrion

Lancet Public Health

Neuroscience

Neuron

J. Pharm. Sci.

J. Psychiatr. Res.

Vasc. Pharmacol.

Trends Mol. Med.

Global DNA methylation analysis of human atherosclerotic plaques reveals extensive genomic hypomethylation and reactivation at imprinted locus 14q32 involving induction of a miRNA cluster

Eur. Heart J.

Microbiome, inflammation, epigenetic alterations, and mental diseases

Am. J. Med. Genet. B Neuropsychiatr. Genet.

BDNFVal66met polymorphism: a potential bridge between depression and thrombosis

Eur. Heart J.

The genetic overlap between mood disorders and cardiometabolic diseases: a systematic review of genome wide and candidate gene studies

Transl. Psychiatry

HTR1A a novel type 1 diabetes susceptibility gene on chromosome 5p13-q13

PLoS One

Does the MTHFR C677T gene polymorphism indicate cardiovascular disease risk in type 2 diabetes mellitus patients?

Anatol. J. Cardiol.

Proteomic analysis of the anterior cingulate cortex in the major psychiatric disorders: evidence for disease-associated changes

Proteomics

Neuroanatomical pattern of mitochondrial complex I pathology varies between schizophrenia, bipolar disorder and major depression

PLoS One

The repressor element 1-silencing transcription factor regulates heart-specific gene expression using multiple chromatin-modifying complexes

Mol. Cell. Biol.

Epigenetic regulation of toll-like receptor signaling: implications for cancer development

Med. Epigenetics

Association study of CREB1 polymorphisms and suicidality in MDD: results from a European multicenter study on treatment resistant depression

Int. J. Neurosci.

The mitochondrial side of epigenetics

Physiol. Genomics

DNA methylation indicates susceptibility to isoproterenol-induced cardiac pathology and is associated with chromatin states

Circ. Res.

Brain-heart interaction: cardiac complications after stroke

Circ. Res.

Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution

Science

The role of epigenetic mechanisms in the regulation of gene expression in the nervous system

J. Neurosci.