ABSTRACT

The serotonergic system has been shown to be affected in a number of psychiatric illnesses in the last 50 years. A large body of work has focused on serotonin (5-HT) de”cits in major depressive disorder (MDD) and suicide. A great deal has been learned about the anatomy, development, and functional organization of the 5-HT system and the alterations in this system that are present within the suicide brain. Historically, evidence for the involvement of 5-HT in suicide stemmed from ”ndings of low cerebral spinal ›uid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) in depressed suicide attempters and in the brain stems of completed suicides (Åsberg 1976; Åsberg et al. 1976; Banki et al. 1984; Carlsson et al. 1980; Mann and Malone 1997; Placidi et al. 2001; Roy et al. 1986; Träskman et al. 1981). Suicide attempters also exhibit a blunted release of prolactin in response to administration of fen›uramine, a measure of 5-HT activity (Dulchin et al. 2001; Duval et al. 2001; Malone et al. 1996; Mann et al. 1995; Pandey 1997; Weiss and Coccaro 1997). These studies provided evidence for de”cits in serotonergic neurotransmission in the brain stem or serotonergic targets in the forebrain of suicidal individuals. 5-HT is produced by neurons embedded in the midline raphe nuclei in the brain stem with widespread targets that appear to be topographically organized. In this chapter, we will discuss data that shed light into the contribution of these serotonergic neurons to brain diseases such as MDD and suicide.