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.