Vicious Circle in the Brain

22. August 2007

In the course of a malignant tumor ailment 25 percent of the patients develop a depression. Several studies proved this. Now it turns out that the psychological pressure of the disease is not the actual trigger. It's the neurotransmitters that are out of balance.

For a long time a pessimistic attitude was assumed to influence the process of a malignant negatively. Researches now have shown that organic reasons are behind it. A disturbance of the neurotransmitter balance is the main reason for the development of a depression. Mainly the lack of availability of the protein module Tryptophan is associated with a tendency to depression: A lack of Tryptophan influences the generation of the happiness hormone Serotonin.

The tricks of the immune system

The discovery was more coincidentally: "The immune system does all sorts of things to block the growths of malignant cells", explains Univ.-Prof. Mag. Dr. phil. Dietmar Fuchs of the institute for biological chemistry at the medical university of Innsbruck.

For years his working group is studying the connection between immune reaction, Tryptophan metabolism and psychology. "A large part of the mechanisms is targeting to block the growth of the cells – one of it is the withdrawal of Tryptophan. The synthesis of Serotonin proceeds from the amino acid Tryptophan: the enzyme Tryptophan-(5)-Hydroxylase metabolizes it to Serotonin, aside with a metabolization of Tryptophan via the kynurenine. The group was able to identify low concentrations of Tryptophan and high ones of kynurenine in the plasma of patients suffering from malignant tumors, in particular on patients in an advanced stage of the disease.

During a study made on adults suffering from T-cell leukemia the scientists observed that lower Tryptophan levels went along with a lower probability to survive. Similar results showed in patients with colon carcinoma and outside tumor diseases in for example HIV infections and various autoimmune diseases.Here patients with a better prognosis display a lower consumption of Tryptophan.

The more aggressive the tumor, the stronger the depression

"A tumor develops if the immune system is too weak to ward it off", explains Fuchs. "In tumor patients, the immune system reduces the availability of Tryptophan by cutting the amino acid to stop the tumor from growing." Due to the mutual immunological background physicians found an increased level of Neoptrin but also decreased Tryptophan- and Serotonin concentrations in the plasma in patients with malignant tumors. The reduction of Tryptophan as well as the Neoptrin production seem even stronger the more aggressive the tumor. "The strain on the immune system is heavier", says Fuchs.

This results in a stronger impoverishment in Tryptophan. We presume that lower Tryptophan levels and higher Neoptrin levels appear before the actual diagnosis since those changes are detectable in the plasma during the diagnosis and before a specific tumor therapy. This would mean that an existing, but clinically not manifested tumor activity leads to an intensified Tryptophan reduction at a point of time when the tumor is not detectable yet by clinical means.

Tumor unleashes mood swings

"We cannot say for sure whether the prognosis for a tumor could be improved by evening up the Tryptophan", explains Fuchs. "The basic disease for sure has to be treated with established therapies". But Fuchs' main concern is the understanding of depressed tumor patients. "It does make a difference for the patient to know that the depression is caused by the disease and not by a psychological weakness – which often is insinuated."

The results show that a malignant process can be triggered by a stimulation of the immune system and the related increased reduction of Tryptophan, thus causing mood swings. The patient handles bad news less good than a healthy person. It is not the tendency for depression which is responsible for the developing of malignant tumor – it is the tumor that is responsible for the development of a pessimistic attitude towards life. "If we succeeded in healing the tumor", says Fuchs, "the Tryptophan household would balance and heal the depressions all by itself and long-term."

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