Serotonin-immune interactions in major depression: Lower serum tryptophan as a marker of an immune-inflammatory response

Serum total tryptophan and the five competing amino acids (CAA), i.e., valine, leucine, tyrosine, phenylalanine, and isoleucine were determined in 35 major depressed subjects of whom 27 with treatment resistant depression (TRD), and 15 normal controls. Twenty-five of the depressed subjects had repeated measurements of the amino acids both before and after antidepressive treatment. The following immune-inflammatory variables were assayed in the above subjects: serum zinc (Zn), total serum protein (TSP), albumin (Alb), transferrin (Tf), iron (Fe), high-density lipoprotein cholesterol (HDL-C), number of peripheral blood leukocytes, and the CD4(+)/CD8(+) T cell (T-helper/T-suppressor) ratio. Serum tryptophan and the tryptophan/CAA ratio were significantly lower in major depressed subjects than in normal controls. The tryptophan/CAA ratio was significantly lower in patients with TRD than in patients without TRD and normal controls. There were no significant alterations in any of the amino acids upon successful therapy. There were significant correlations between serum tryptophan and serum Zn, TSP, Alb, Tf, Fe, and HDL-C (all positive), and number of leukocytes and the CD4(+)/CD8(+) T-cell ratio (all negative). The tryptophan/CAA ratio was significantly and negatively related to the number of leukocytes and the CD4(+)/CD8(+) T-cell ratio. The results suggest that (a) TRD is characterized by lower availability of serum tryptophan; (b) the availability of tryptophan may remain decreased despite clinical recovery; and (c) the lower availability of tryptophan is probably a marker of the immune-inflammatory response during major depression.