Low serotonin (5-hydroxytryptamine, 5-HT) neurotransmission is hypothesized in the pathophysiology of suicide (for review see Bach and Arango, 2012; Mann, 2003; Träskman et al., 1981). Cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA) in depressed suicide attempters is lower compared to controls (Lidberg et al., 2000; Mann et al., 1996; Mann and Malone, 1997; Placidi et al., 2001; Träskman et al., 1981). In four out of five postmortem studies of brainstem (Beskow et al., 1976; Bourne et al., 1968; Lloyd et al., 1974; Pare et al., 1969; Shaw et al., 1967), suicides had less 5-HT or 5-HIAA compared to controls. In contrast, most postmortem studies report no differences in cortical 5-HT or 5-HIAA in suicides compared to controls (Arango and Mann, 1992; Arato et al., 1987; Arranz et al., 1997; Beskow et al., 1976; Cochran et al., 1976; Mahadik et al., 1988).

5-HT in the forebrain is synthesized by brainstem dorsal and median raphe nuclei (DRN and MRN) 5-HT neurons. Tryptophan hydroxylase 2 (TPH2) is the neuron-specific, rate-limiting enzyme for the synthesis of 5-HT (Alenina et al., 2009; Patel et al., 2004; Zhang et al., 2004). We found more 5-HT neurons (Underwood et al., 1999), more TPH2 protein (Boldrini et al., 2005; Underwood et al., 1999) and mRNA (Bach-Mizrachi et al., 2006; Bach-Mizrachi et al., 2008) in DRN and MRN of suicides. We sought to reconcile these three sets of observations in suicides: low 5-HIAA or 5-HT in brainstem, unchanged levels in the cortex and more 5-HT neurons containing more TPH2. We therefore performed a pilot study measuring 5-HT and 5-HIAA by high pressure liquid chromatography (HPLC), sampling the brainstem along the axis of DRN and MRN, and in dorsolateral prefrontal cortex (PFC), in unmedicated controls and depressed suicides, with postmortem intervals of less than 24 hours.