5-Hydroxytryptamine (5-HT) in the whole-blood of patients with depressive illness.

Introduction Many, but not all, investigations point to a decrease in 5-hydroxytryptamine (5-HT) synthesis in depressive illness (Coppen, 1972; Lapin and Oxenkrug, 1969). Thus, the concentration of brain 5-hydroxyindole acetic acid (5-HIAA) has been reported decreased in the brains of depressive suicides (Shaw, Camps and Eccleston, 1967; Boume et al., 1966; Pare etal., 1969). The concentration of5-HIAA in lumbar cerebrospinal fluid in depressive patients has been reported decreased both before and after the administration of probenecid (Coppen et al., 1972; Ashcroft et al., 1966; Van Praag, Korf and Puite, 1970; Sjostr6m, 1974). The value ofmany of these investigations is limited by the difficulties in providing well controlled experiments because of the obvious difficulties in obtaining a random sample of healthy subjects of comparable age and sex for either the post-mortem studies or the cerebrospinal fluid studies. More recently the authors have been examining the concentration of free plasma-tryptophan which is an important factor in determining the concentration of brain tryptophan (Tagliamonte, Biggio and Gessa, 1971). The concentration of brain tryptophan is an important factor in determining the rate of brain 5-HT synthesis as the enzyme tryptophan hydroxylase is not normally saturated in the mammalian brain (Tagliamonte et al., 1973; Fernstrom and Wurtman, 1971). In an initial investigation (Coppen, Eccleston and Peet, 1973) free plasma-tryptophan was found to be significantly decreased in female depressive patients, although this returned towards normal after clinical recovery. These findings have been confirmed (unpublished) in a further group of female depressives, and the findings have also been independently confirmed by Aylward (1973), who also reported a correlation between free plasma-tryptophan concentration and clinical improvement. If there is a decrease in free plasma-tryptophan, other organs than the brain synthesizing 5-HT should show a decreased synthesis of this compound; 5-HT is produced in many other organs, including the gut, kidney, liver, lungs. Most 5-HT that reaches the blood stream is transported by the blood platelets, and little 5-HT is detectable in the blood outside the platelets. Whole-blood estimates of blood 5-HT are essentially measures of platelet 5-HT. A study of whole blood 5-HT was undertaken to see if any change in whole body 5-HT synthesis rates would be reflected in a change in blood 5-HT of patients suffering from a depressive illness.