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INTRODUCTION: An involvement of the central serotonergic system has been reported in the pathogenesis of suicide. The dorsal raphe nucleus (DRN) is the main source of serotonergic innervation of forebrain limbic structures disturbed in suicidal behavior, in which an abnormal reaction of microglial cells seems to play an important role. AIM(S): In our present study, the densities of microglial cells immunostained for the HLA-DR antigen were evaluated in the DRN. METHOD(S): These analyses were carried out on paraffin-embedded brains from 24 suicidal patients and 21 non-suicidal patients; among them 27 depressed patients (15 major depressive disorder and 12 bipolar disorder), 18 schizophrenia patients (9 residual, 9 paranoid), and 22 matched healthy control subjects. RESULTS: Only the non-suicidal depressed subgroup revealed a significantly lower microglial reaction. This means that we found a decreased density of HLA-DR immunopositive microglia compared with those of both depressed suicide victims and healthy control subjects. This effect was not related to antidepressant or antipsychotic medication, as the former correlated positively with microglial density in non-suicidal depressed patients, and the latter had no effect. CONCLUSIONS: Moreover, the comparison of these results with previously published data from our workgroup in the same cohort suggested a positive impact of microglia on ribosomal DNA transcription in DRN neurons in the non-suicidal depressed subgroup, but not in depressed suicidal cases. Therefore, the interaction between microglia and neurons in the DRN may be potentially involved in opposite ways regarding suicide facilitation and prevention in the tested subgroups of depressed patients. FINANCIAL SUPPORT: This research was funded by the Otto-von-Guericke-University of Magdeburg and the Medical University of Gdansk.