Postmortem Investigation of Serotonergic and Peptidergic Hypotheses of Affective Illness

Abstract

Some pharmacological^1,2 and neuroendocrinological³ data support the notion that in depression there is an increase in postsynaptic serotonin (5-hydroxytryptamine, 5-HT) receptor function consequent to a diminished presynaptic availability of 5-HT. Each of these lines of evidence has been criticized, and all are indirect. An alternative approach has been to examine parameters of serotonergic function in postmortem tissue. Studies to date have largely involved suicide cases. Conflicting results on 5-hydroxyindoleacetic acid (5-HIAA) levels and 5-HT receptors have been reported.⁴ Mann et al.⁵ reported a significant increase in the number of 5-HT sites in drug-free suicides compared with matched controls, but this was not replicated in another study.⁶ Such discrepancies may arise from the use of data from suicide patients, a heterogeneous group for whom clinical documentation is often lacking and of whom fewer than half may have a history of affective disorder.⁴