Suicide and depression are associated with reduced serotonergic neurotransmission. In suicides, there is a reduction in serotonin transporter (SERT) sites and an increase in postsynaptic 5-HTReduced serotonergic function in the brain of suicide victims is suggested based on findings of lower brainstem levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), as well as fewer serotonin transporter (SERT) binding sites and more post-synaptic 5-HT 1A receptors in prefrontal cortex in suicide victims (see Mann et al. 2000 for review). In suicide victims, the changes in SERT and 5-HT 1A binding are NO . 6 Serotonin Transporter in the DRN of Suicides 893 localized to the ventral PFC (Arango et al. 1995), an area involved in behavioral inhibition (Damasio et al. 1994) and, therefore, the potential location of a diathesis for suicidal behavior. Studies in depressed suicide attempters compared to psychiatric controls have found lower cerebrospinal levels of 5-HIAA (Mann and Malone 1997). In vivo studies have employed pharmacological challenges that activate brain serotonin receptors invoking release of prolactin that can be measured in the blood Malone et al. 1996) or a change in regional glucose metabolism in the brain that can be measured by positron emission tomography (Malone et al. 2000). Results of these studies indicate blunted responses to 5-HT and support the notion of serotonin deficiency in depressed suicidal patients. Importantly, the relationship of serotonin hypofunction to suicidal acts is independent of psychiatric diagnosis (Mann et al. 1989;Stanley et al. 2000;Coccaro et al. 1989).The most widely reported serotonergic abnormality in major depression involves fewer platelet serotonin transporter sites (Owens and Nemeroff 1994). In vivo imaging (Malison et al. 1998;Willeit et al. 2000) and postmortem brain studies (Perry et al. 1983;Arango et al. 1995;Mann et al. 2000) conducted in depressed patients suggest that less SERT binding is more widespread in the brain compared with suicides, and includes the brainstem. One potential cause for fewer SERT sites, in the prefrontal cortex and elsewhere, would be a reduction in SERT gene expression. SERT mRNA is expressed in 5-HT neurons in the brainstem.We previously reported (Austin et al. 1994) the first anatomical visualization of human brain serotonin transporter gene expression and described the localization of the SERT mRNA to the serotonergic neurons of the dorsal raphe nucleus (DRN) and median raphe nucleus (MRN). In rodents, non-human primates, and presumably humans, it is the dorsal and median raphe nuclei that provide the serotonergic innervation of the entire forebrain (Wilson and Molliver 1991a,b;Bobillier et al. 1975Bobillier et al. , 1976Sakai et al. 1977).In the DRN, the 5-HT 1A receptor is a somatodendritic inhibitory autoreceptor on 5-HT neurons (Vergé et al. 1985;Middlemiss and Fozard 1983). 5-HT released locally acts on the autoreceptor to inhibit further release of the 5-HT transmitter (Wang and Aghajanian 1977). Altered autoinhib...