Reduced ribosomal DNA transcription in the prefrontal cortex of suicide victims: consistence of new molecular RT-qPCR findings with previous morphometric data from AgNOR-stained pyramidal neurons.

Prefrontal cortical regions play a key role in behavioural regulation, which is profoundly disturbed in suicide. The study was carried out on frozen cortical samples from the anterior cingulate cortex (dorsal and ventral parts, ACd and ACv), the orbitofrontal cortex (OFC), and the dorsolateral cortex (DLC) obtained from 20 suicide completers (predominantly violent) with unknown psychiatric diagnosis and 21 non-suicidal controls. The relative level of ribosomal RNA (rRNA) as a marker of the transcriptional activity of ribosomal DNA (rDNA) was evaluated bilaterally in prefrontal regions mentioned above (i.e. in eight regions of interest, ROIs) by reverse transcription and quantitative polymerase chain reaction (RT-qPCR). The overall statistical analysis revealed a decrease in rDNA activity in suicide victims versus controls, particularly in male subjects. Further ROI-specific post hoc analyses revealed a significant decrease in this activity in suicides compared to non-suicides in five ROIs. This effect was accentuated in the ACv, where it was observed bilaterally. Our findings suggest that decreased rDNA transcription in the prefrontal cortex plays an important role in suicide pathogenesis and corresponds with our previous morphometric analyses of AgNOR-stained neurons.

Ribosomal DNA transcription in prefrontal pyramidal neurons is decreased in suicide.

Prefrontal cortical regions, which are crucial for the regulation of emotionally influenced behaviour, play most probably a dominant role in the pathogenesis of suicide. The study was carried out on paraffin-embedded brain tissue blocks containing specimens from the anterior cingulate cortex (dorsal and ventral parts), the orbitofrontal cortex, and the dorsolateral cortex obtained from 23 suicide completers (predominantly violent) with unknown psychiatric diagnosis and 25 non-suicidal controls. The transcriptional activity of ribosomal DNA (rDNA) as a surrogate marker of protein biosynthesis was evaluated separately in layers III and V pyramidal neurons in regions of interest (ROIs) mentioned above by the AgNOR silver staining method bilaterally. The overall statistical analysis revealed a decrease of AgNOR area suggestive of attenuated rDNA activity in suicide victims versus controls, particularly in male subjects. Further ROI-specific post-hoc analyses revealed decreases of the median AgNOR area in suicides compared to non-suicides in all 16 ROIs. However, this effect was only significant in the layer V pyramidal neurons of the right ventral anterior cingulate cortex. Our findings suggest that decreased rDNA transcription in prefrontal pyramidal neurons plays possibly an important role in suicide pathogenesis.