Chronic immune stimulation may link ischemic heart disease with depression.

Content Provider	Semantic Scholar
Author	Murr, Christian Ledochowski, Maximilian Fuchs, Dietmar
Copyright Year	2002
Abstract	Heart Disease With Depression To the Editor: Carney et al1 reported that greater autonomic heart dysfunction, as reflected by decreased heart rate variability, is a plausible mechanism linking depression to increased cardiac mortality in post–myocardial infarction patients. We want to discuss another possible pathomechanism that might contribute to the fact that depression is an independent risk factor for increased mortality and morbidity after myocardial infarction: from several studies, it is evident that atherosclerotic disease is associated with continuous activation of immunological pathways. Among other markers of immune activation and inflammation, elevated concentrations of neopterin, an indicator of Th1-type immune activation, C-reactive protein, or serum amyloid A are found in plasma of patients with acute or chronic coronary syndromes, indicating the inflammatory nature and correlating with the severity of atherosclerotic disease.2 Increased formation of interferonduring Th1-type immune response is associated with activation of the enzyme indoleamine (2,3)-dioxygenase (IDO) in a variety of cells including monocytes/macrophages.3 IDO converts the essential amino acid tryptophan to kynurenine within the biosynthetic pathway of nicotinamide-adenine dinucleotide. Because tryptophan is a precursor for the biosynthesis of the neurotransmitter 5-hydroxytryptamine ( serotonin), low tryptophan concentration is associated with decreased availability of serotonin, which finally increases the susceptibility for the development of mood disturbances and depression in the patients.3,4 Increased production of neopterin concomitant with activation of IDO resulting in lower serum tryptophan and higher kynurenine concentrations was found in patients with various immunopathological conditions3 and also in patients with hypertrophic and dilated cardiomyopathy, the changes correlating with left ventricular function tests.5 With this background, decreased plasma tryptophan concentrations should parallel the changes of immune activation markers also in atherosclerotic disease; then the development of depression in patients with ischemic heart disease could easily result from chronic immune stimulation and concomitant depletion of tryptophan. We conclude, in patients with ischemic heart disease, a more severe atherosclerotic disease will be associated with a more drastic challenge of the immune system, which is responsible for worse outcome. A higher susceptibility for depression will then result form a parallel depletion of tryptophan and neurotransmitter disturbances.
Starting Page	e83
Ending Page	e83
Page Count	1
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://circ.ahajournals.org/content/circulationaha/105/14/e83.full.pdf?download=true
PubMed reference number	11940560v1
Volume Number	105
Issue Number	14
Journal	Circulation
Language	English
Access Restriction	Open
Subject Keyword	Adenine Amino Acids Amino Acids, Essential Anabolism Atherosclerosis Biosynthetic Pathways Bradycardia C-reactive protein Cardiomyopathies Cardiomyopathy, Dilated Depressive disorder Dinucleoside Phosphates Flavin-Adenine Dinucleotide Heart Diseases Heart failure Hypertrophy Immune system Inflammation Kynurenine Left Ventricular Function Mood Disorders Morbidity - disease rate Myocardial Infarction Myocardial Ischemia Neopterin Neurotransmitters Niacin Paget's Disease, Mammary Parkinson Disease Patients Serotonin Serum amyloid A protein Syndrome Tryptophan
Content Type	Text
Resource Type	Article