Abstract
An involvement of the central serotonergic system has been implicated in the pathogenesis of suicide. The dorsal raphe nucleus (DRN) is the main source of serotonergic innervation of forebrain limbic structures disturbed in suicidal behaviour. The study was carried out on paraffin-embedded brainstem blocks containing the DRN obtained from 27 suicide completers (predominantly violent) with unknown psychiatric diagnosis and 30 non-suicidal controls. The transcriptional activity of ribosomal DNA (rDNA) in DRN neurons as a surrogate marker of protein biosynthesis was evaluated by the AgNOR silver staining method. Significant decreases in AgNOR parameters suggestive of attenuated rDNA activity were found in the cumulative analysis of all DRN subnuclei in suicide victims versus controls (U test P values < 0.00001). Our findings suggest that the decreased activity of rDNA transcription in DRN neurons plays an important role in suicide pathogenesis. The method accuracy represented by the area under receiver operating characteristic curve (>80 %) suggests a diagnostic value of the observed effect. However, the possible application of the method in forensic differentiation diagnostics between suicidal and non-suicidal death needs further research.Electronic supplementary materialThe online version of this article (doi:10.1007/s00406-015-0655-4) contains supplementary material, which is available to authorized users.
Highlights
Disturbances of the central serotonergic system are implicated in a multifaceted way in suicidal behaviour, which has been proposed to be an independent mental disorder in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders—DSM V [3] in accordance with numerous neurobiological research data.As revealed by neuropathological research on suicide, abnormalities in the serotonergic system may be structurally restricted to a specific brain region, the dorsal raphe nucleus (DRN), which affects brain circuits
The majority of investigated cases (17 suicide victims and 28 controls, see Supplementary Table) revealed the blood alcohol concentration (BAC) below the limit of quantification (LOQ), i.e.
The differences in AgNOR parameters were beyond qualitative evaluation, and they could only be captured by means of quantitative measurements
Summary
As revealed by neuropathological research on suicide, abnormalities in the serotonergic system may be structurally restricted to a specific brain region, the dorsal raphe nucleus (DRN), which affects brain circuits (for a review see: [4]). Limbic regions of the PFC (i.e. the anterior cingulate cortex and the orbitofrontal cortex) in turn may reciprocally regulate DRN function through direct pyramidal input [8, 9] modulated by serotonergic receptors in the PFC (for reviews see: [10,11,12,13]). A number of post-mortem studies revealed changes in the DRN of suicide victims [14,15,16,17,18,19,20,21,22,23,24,25,26,27,28]. Inconsistencies regarding psychiatric diagnosis, treatment, cause of death, the delineation of investigated areas, Eur Arch Psychiatry Clin Neurosci (2016) 266:217–224 methodical issues and small sample sizes seem to be the most significant [29]
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