Eighteen unmedicated patients suffering from
major depressive disorder with
melancholia (DSM-III) were examined for abnormalities in peripheral
serotonin (5-HT) and related metabolites.
Serotonin in platelet-free plasma and in platelets from melancholics was significantly reduced to 30% and 60% of their respective control values. Plasma 5-hydroxyindoleacetic
acid was also found to be reduced, but not significantly. Other plasma compounds related to
5-HT (
indoleacetic acid, total
tryptophan, and free
tryptophan) were found to be unchanged in these patients. Of all variables, only platelet
5-HT was affected while patients were on
clomipramine (CIM) treatment. After 2 weeks on CIM (100-150 mg/day, orally), platelet
5-HT was reduced to 8% of pretreatment values, but plasma
5-HT did not change and continued to be reduced upon clinical recovery. The existence of a distinct pool of plasma
5-HT that is clearly independent of the platelet pool is indicated by the differences observed in plasma and platelet
5-HT during CIM treatment, as well as by previous data from this laboratory. The very marked decrease in plasma
5-HT levels may be in accord with the central nervous system changes reported in depression and suggests the possibility of using plasma
5-HT as a peripheral
indicator of abnormal
serotonin function in
melancholia.