Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy.
Mol Psychiatry. 2002-06-01; 7(5): 468-473
DOI: 10.1038/sj.mp.4000995
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1. Mol Psychiatry. 2002;7(5):468-73.
Association between decreased serum tryptophan concentrations and depressive
symptoms in cancer patients undergoing cytokine therapy.
Capuron L(1), Ravaud A, Neveu PJ, Miller AH, Maes M, Dantzer R.
Author information:
(1)INSERM-INRA, Integrative Neurobiology, Institut François Magendie, 33077
Bordeaux, France.
Comment in
Mol Psychiatry. 2002;7(5):429.
Cytokine therapy for cancer or viral diseases is accompanied by the development
of depressive symptoms in a significant proportion of patients. Despite the
increasing number of studies on the neurotoxic effects of cytokines, the
mechanisms by which cytokines induce depressive symptoms remain largely unknown.
In view of the relationship between neurotransmitter precursors and mood, the
present study aimed at assessing the relationship between serum concentrations of
the amino acids tryptophan and tyrosine, major precursors of serotonin and
norepinephrine respectively, and depressive symptoms in cancer patients
undergoing cytokine therapy. Sixteen cancer patients eligible to receive
immunotherapy with interleukin-2 and/or interferon-alpha participated in the
study. At baseline and after one week and one month of therapy, depressive
symptoms were assessed using the Montgomery-Asberg Depression Rating Scale
(MADRS), and blood samples were collected for the determination of the large
neutral amino acids (LNAA) (tryptophan, tyrosine, valine, leucine, isoleucine,
phenylalanine) which compete for transport across the blood-brain barrier. Serum
concentrations of tryptophan as well as the tryptophan/LNAA ratio significantly
decreased between baseline, one week and one month of therapy. The development
and severity of depressive symptoms, especially anorexia, pessimistic thoughts,
suicidal ideation and loss of concentration were positively correlated with the
magnitude of the decreases in tryptophan concentrations during treatment. These
findings indicate that the development of depressive symptoms in patients
undergoing cytokine therapy could be mediated by a reduced availability of the
serotonin relevant amino acid precursor, tryptophan.
DOI: 10.1038/sj.mp.4000995
PMID: 12082564 [Indexed for MEDLINE]