Serotonin receptor sensitivity in major depression

Abstract

Research on the role of serotonin (5-hydroxytryptamine, 5HT) in depression spans well over two decades. The most consistc~t finding is that the cerebrospinal fluid (CSF) concentration of the 5HT metabolite, 5-hydroxyindoleacetic acid (SHIAA) is lowered in about ,..10% of patients with major depression (MD) (review: Kalus et al. 1989). The fall of CSF 5HIAA levels suggests a decrease of 5HT metabolism in the CNS, which may be the result of, or lead to, increased 5HT receptor sensitivity. Studies examining 5HT receptor sensitivity, however, have provided conflirting results. One study reported increased 5HT receptor sensitivity in MD, using the 5HT precursor, 5-hy&'oxytryptophan (5HTP) as a 5HT challenger (Meltzer etal. 1984). However, Westenberg et al. (1982), using the same oral dose of 5HTP in combination with a decarboxylase inhibitor, found normal responses in depressed subjects..qty.!dies using tryptophan and fenfluramine as 5HT challenge agents found decreased (Heninger et al. 1984; Siever et al, 1984; Coctaro et al. 1989) or normal (Asnis et al. 1988) 5HT receptor sensitivity in depressed patients. The conflicting findings may be the result of the nonselectivity of these agents and their indirect stimuiation of 5HT receptors (van Praag et al. 1987). in contrast to the studies reviewed above, the