Association between increased tryptophan degradation and depression in cancer patients

Abstract

A high percentage of patients with malignant disease develops mood disorders or even depression. This review provides an overview, how immune activation and tryptophan degradation might contribute to the development of depression. Neurobiochemical changes caused by immune activation are supposed to be involved in the development of mood disorders, especially depression, in cancer patients. Within Th1-type immune response the enzyme indoleamine 2,3-dioxygenase (IDO) is induced, which degrades the essential amino acid tryptophan to form kynurenine derivatives. Enhanced immune-mediated tryptophan degradation is reflected by decreased plasma tryptophan levels and increased kynurenine concentrations in parallel with elevated concentrations of Th1-type immune activation marker neopterin. IDO activation has been demonstrated in patients with various kinds of cancer, and it has also been shown to predict a worse outcome of patients. Recent data also indicate strongly, that immune-mediated tryptophan degradation is crucially involved in the development of depression: IDO activation leads to the accumulation of neurotoxic metabolites, which are supposed to induce depressive-like behaviour. Furthermore immune-mediated tryptophan deprivation might also impair serotonin synthesis, as tryptophan is the precursor of this important neurotransmitter. Immune-mediated tryptophan degradation appears to be crucially involved in the development of depression.