was funded by a Wellcome Trust Oxford Neurosciences M.Sc./D.Phil. diagnosis or suicide. No changes were seen in schizophrenia. == Conclusion == The results show that mood disorders and suicide are associated with differential, limited morphological alterations of the DRN. The contrasting influences of MDD and suicide may explain some of the discrepancies between previous studies, since their design precluded detection of the effect. Keywords:5-HT1A receptor, HTR1A, Morphometry, Serotonin, Tryptophan hydroxylase == 1. Introduction == The 5-hydroxytryptamine (5-HT; serotonin) neurons that innervate the forebrain lie in the rostral raphe nuclei of the brainstem (Hornung, 2003; Molliver, 1987), with the dorsal raphe (DRN) being the largest nucleus (Baker et al., 1991). The DRN provides the main input to the frontal cortex (McQuade and Sharp, 1997) and an enlarged lateral subdivision characterises primates, including man (Hornung, 2003). In the DRN cells projecting to prefrontal cortex are preferentially found in more rostral, medial, and ventral Protodioscin subdivisions, and around half are non-serotonergic (Del Cid-Pellitero and Garzn, 2011; Wilson and Molliver, 1991). Afferent projections to the DRN are primarily from your limbic system (Hornung, 2003) but there is also a reciprocal innervation of the DRN from prefrontal cortex which modulates neuronal activity (Celada et al., 2001). The 5-HT system has been implicated in many psychiatric disorders, including mood disorders (Barton et al., 2008; Deakin, 1998; Jans et al., 2007; Mahmood and Silverstone, 2001), and in suicide (Ernst et al., 2009; Mann et al., 1989; Placidi et al., 2001). The evidence is diverse, and includes alterations in 5-HT metabolism, 5-HT receptors and transporters, and associations with serotonergic gene polymorphisms. There is also evidence of decreased neuronal density and serotonergic abnormalities in prefrontal cortex of stressed out suicides (Underwood et al., 2011). In contrast, the morphology and cytoarchitecture of the DRN in these disorders have received limited attention. The existing studies have utilised standard staining (Baumann et al., 2002; Underwood et al., 1999), or antibodies detecting tryptophan hydroxylase (TPH) to identify 5-HT neurons (Hendricksen et al., 2004; Syed et al., 2005; Underwood et al., 1999); there are also studies which have used other 5-HT markers (e.g. 5-HT1Aautoreceptors;Arango et al., 2001; Boldrini et al., 2008; Stockmeier et al., 1998), or a marker of raphe neuron activation (Bielau et al., 2005). The studies have produced variable results, likely reflecting both methodological and clinical factors. For example, as well as measuring different parameters, and using numerous DRN sampling strategies, the studies are small, and differ in the subjects age, polarity of mood Protodioscin disorder, and presence of comorbid conditions. This investigation was performed to help shed some further light around the involvement of the Protodioscin DRN in MGC18216 the neuropathology of mood disorder and suicide. It has a larger sample size than existing studies; it includes patients from three diagnostic groups (major depressive disorder [MDD], bipolar disorder, and schizophrenia, as well as suicides and non-suicides within each group), and uses three complementary techniques: NeuN to assess all neurons, and TPH immunohistochemistry and 5-HT1AR mRNA in situ hybridization (ISH) as markers of serotonergic neurons. == Protodioscin 2. Materials and methods == == 2.1. Subject and tissue characteristics == Unfixed frozen 14 m sections of brainstem Protodioscin were provided by the Stanley Neuropathology Consortium from their series of 60 subjects diagnosed (by DSM-IV criteria) with schizophrenia, bipolar disorder or MDD, and controls (Torrey et al., 2000). In each diagnostic group some subjects died by suicide. The sections provided were quite rostral, and tissue from ten subjects did not contain sufficient clearly discernible DRN to be included.Table 1summarises the details of the resulting 50 subjects. Adjacent sections were taken for NeuN and PH8 immunostaining every 1 mm, and 1 section every 500 m for 5-HT1AR ISH. The experiments described here, were carried out with ethical approval from Oxfordshire Research Ethics Committee B (#O02.040). All material was coded by the Stanley Medical Research Institute, and.