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Is there a common genetic link for depression and cardiovascular disease?

Molecular Psychiatry

A large body of evidence has emerged over several years for an association between depressive disorder and cardiovascular disease. Although many studies have shown that depression increases the risk for coronary artery disease and the mortality rates after myocardial infarction, there is recent support for the assumption that the relation between both disorders may be bi-directional. The mechanisms of this interaction are at present uncertain and several factors, including stress with its multiple actions on brain and peripheral organs, acute inflammatory reactions with altered immune function as well as a genetically driven susceptibility to develop the disorders are under debate.

Regarding the genetic contribution, variants in two genes were repeatedly discussed as important predisposing factor for cardiovascular function and disease. The gene coding for the angiotensin-converting-enzyme (ACE), an enzyme which is involved in the development of hypertension and other cardiovascular distress, has a common mutation (allele-D) which results in increased ACE concentration (consequently, ACE inhibitors are used as antihypertensive agents). Several studies have shown an association between this allele-D and cardiovascular disorders, supporting the hypothesis of a genetic contribution. However, not only the actual concentration of ACE but also other factors are relevant for cardiovascular function and the development of diseases. Among those is the transduction of nervous signals, which is regulated by various components, including G-proteins. G-proteins are located within the cellular membranes and are thus key elements for the signal transduction, as they induce a cascade of cell reactions after the incoming signal. Thus alterations in the function of these G-proteins could have tremendous effects upon rapidity and quality of the nervous signal transmission. And recently a mutation in one subtype of these G-protein genes, the G-ß3 subunit allele-T was observed not only in obesity but also in patients with hypertension. Moreover, the combination of these two variants of the ACE and G-ß3 genes have recently been shown to increase the risk for myocardial infarction. Interestingly, both proteins and their genes are not only relevant in periphery for cardiovascular disorders, but have also impact on many aspects of brain function and for the development of psychiatric disorders, including depression. Thus, in a previous investigation study the authors had shown, that the G-ß3-T allele was more frequent among depressive patients, although they were not hypertensive.

The aim of the present study was to figure out whether a combination of both gene variants might be important also in depression and could thus be a link between both disorders. Researchers in Germany have carried out a combined analysis of the allelic variants of the ACE and G-ß3 genes in a cohort of 201 patients with severe depression and 161 healthy controls. Their data revealed an increased frequency of the combined ACE-D and the G-ß3-T alleles in depressive patients, as 17% of the depressed patients, but only 3% of the controls, had the same allelic combination of those two genes, that were previously shown to increase the risk for myocardial infarction. As these combined alleles are present only in a subset of patients, one might argue that this combination represents a special group of depression, maybe one of older patients with already obvious cardiovascular disturbances. However, this was not the case, as this patient group did not distinguish concerning age, cardiovascular morbidity, depressive symptomatology or other risk factors, such as smoking, cholesterol, blood lipids or the body mass index. Although the authors are presently unable to predict whether this group of patients will develop severe cardiovascular disease or is at increased risk for myocardial infarction, their data do suggest that the increased rates of cardiovascular disease in patients with major depression may at least partly be the result of a gene-gene interaction which is thus predisposing to depression, cardiovascular disease or to both.


Citation source: Molecular Psychiatry 2002 Volume 7, number 10, pages 1120-1126.

Article: Combined action of the ACE D- and G-protein ß3 T-allele in major depression: a possible link to cardiovascular disease?

Authors; Brigitta Bondy, Thomas C. Baghai, Petr Zill, Ronald Bottlender, Markus Jaeger, Cornelius Schuele, Peter Zwanzger, Rainer Rupprecht, Rolf R. Engel

Psychiatry Department, Munich University, Munich, Germany

For further information on this work, please contact Prof. Dr. Brigitta Bondy, Psychiatric Hospital of University Munich, Nussbaumstraße 7, D-80336 Munich, Germany; Phone. 49-89-5160-2737; Fax: 0049-89-5160-4741; e-mail:

Molecular Psychiatry is published by the Nature Publishing Group.

Editor: Julio Licinio, M.D.; phone: 310-825-7113; FAX: 310-206-6715; e-mail:

For a copy of this article and accompanying editorial, please contact Aimee Midei, editorial assistant, e-mail:


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