Research report Differences in activation of the dorsal raphe nucleus depending on performance of suicide Hendrik Bielau a, T ,1 , Christian Mawrin b,1 , Dieter Krell a , Marcus W. Agelink c , Kurt Trqbner d , Richard Davis e , Tomasz Gos a,f , Bernhard Bogerts a , Hans-Gert Bernstein a , Bruno Baumann a a Department of Psychiatry, Otto-von-Guericke-University, Leipziger Strasse 44, 39120 Magdeburg, Germany b Department of Neuropathology, Otto-von-Guericke-University, Magdeburg, Germany c Research Institute of Biological Psychiatry and Neuroscience, Ruhr-University of Bochum, Germany d Institute of Legal Medicine, University of Essen, Germany e Department of Pathology, SUNY Upstate Medical University, Syracuse, NY 13210, USA f Institute of Forensic Medicine, Medical University of Gdansk, Poland Accepted 12 January 2005 Abstract The serotonergic system has been implicated in the pathogenesis of mood disorders as well as in suicidal behavior. It is unknown, however, whether raphe neurons, which are mostly serotonergic, show altered activity in patients with mood disorders who complete suicide as compared to those without suicidal behavior. In order to measure cellular markers of serotonergic activity in the dorsal raphe nucleus in brains of 12 people with mood disorders and of 12 controls (C), stereological measurements were carried out of nucleolar organizer regions (AgNORs) and of serotonergic neuron numbers. Six patients died from suicide (S) and the other six patients died from natural causes (NS). Results were assessed using ANOVA and post hoc Tukey–HSD tests looking for effects of diagnostic group (S, NS, C). Results show that in the rostral subnuclei of the dorsal raphe there was a significant effect of diagnostic group on the ratios of the nucleolar organizer regions to nuclear area (NOR ratio) and a nearly significant effect on numbers of serotonergic neurons. Post hoc tests revealed larger values for those dependent variables in S compared to NS. Dose equivalents of antidepressants correlated positively with NOR ratios and numbers of serotonergic neurons in the rostral part of the dorsal raphe. In conclusion, the present data suggest that there are functional differences in the dorsal raphe of patients with mood disorders depending on suicidal behavior. Antidepressants appear to contribute to cellular activation in the rostral part of the dorsal raphe. D 2005 Elsevier B.V. All rights reserved. Theme: Disorders of the nervous system Topic: Neuropsychiatric disorders Keywords: Nucleolar organizer region; Suicide; Major depression; Neuromorphometry; Dorsal raphe nucleus 1. Introduction Suicide is a major public health problem, accounting for 1–2% of all deaths worldwide [66]. At the time of death, at least 50% of these individuals fulfil the clinical criteria for a depressive disorder [4,18,44]. Several studies have suggested that, especially in patients with mood disorders, suicidal behavior seems to be associated with a deficit in brain serotonergic (5-HT) neurotransmission. Starting in the early 1970s, a number of reports have demonstrated a reduced cerebrospinal fluid concentration of the 5-HT metabolite 5-hydroxyindoleacetic acid in suicide victims [5,8,16,37,51,57]. The impact of the serotonergic neuro- 0006-8993/$ - see front matter D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2005.01.055 T Corresponding author. Fax: +49 391 67 15223. E-mail address: bielau@med.uni-magdeburg.de (H. Bielau). 1 Both authors contributed equally to the work. Brain Research 1039 (2005) 43 – 52 www.elsevier.com/locate/brainres