Link between Heart Disease and Depression: Involvement of ACE Gene
Scientists of the Ludwig Maximilian University Munich arrived at this conclusion in a project of the German Federal Ministry for Education and Research (BMBF), funded in the framework of the National Genome Research Network (NGFN).
In recent years there have been increasing indications that genetic mutations are involved in the development of depression. The ACE gene has emerged as a promising candidate. It was already known that mutations in the ACE gene increase the risk for coronary heart disease, which in turn can promote major depression. The new results now reveal that genetic mutations in the ACE gene also have a direct influence on the development of depression. ACE occurs in the whole organism – even in the central nervous system. Here it is found in substance P-containing neurons, in the basal ganglia and to a lesser extent also in the hypothalamus and other regions of the brain. As in vitro experiments on rodents revealed, ACE not only influences blood pressure, but also the release of hypophysis hormones such as corticotropin.
Interestingly, most patients with major depression have elevated blood plasma concentrations of corticotropin.
A research group of Dr. Thomas Baghai from the Department of Psychiatry and Psychotherapy at Ludwig Maximilian University Munich has now more closely investigated the role of mutations of the ACE gene in the development of major depression. Baghai and his team explored to what extent a genetic relationship exists between 35 single nucleotide polymorphisms or SNPs – in which a nucleotide in the DNA molecule is altered – and the probability of developing major depression. Baghai examined a total of 843 depressive patients and compared their data with those of 1479 healthy control persons. The found associations were confirmed in an additional random test.
In the first screening two SNPs on the ACE gene were significantly associated with major depression. For one of the two SNPs, Baghai and his team could show that this also has functional consequences: It increases the activity of ACE. The data of the Munich scientists indicate very strongly that mutations of the ACE gene promote the development of major depression. “This SNP may represent a pathophysiological connection between depression and cardiovascular disease“, according to Baghai. That would explain the sinister link between mental and cardiac disorders.
