Ribosomal DNA transcription in the anterior cingulate cortex is decreased in unipolar but not bipolar I depression

The anterior cingulate cortex (AC) is consistently implicated in the pathophysiology of depression. However, it is not clear whether unipolar and bipolar depression display distinct neuropathological features. Therefore, the objective of this post-mortem study was to re-evaluate this important issue. Brains from 9 patients with major depressive disorder (MDD) and 11 patients with bipolar disorder (BD) subtype I depression as well as 24 matched controls were analysed. The argyrophilic nucleolar organiser region (AgNOR) silver-staining method was applied on paraffin-embedded brain sections in order to assess the transcriptional activity of ribosomal DNA (rDNA) in layer III and V pyramidal neurons of the dorsal and ventral AC in both hemispheres. An AgNOR area decrease suggestive of a diminished transcriptional activity of rDNA was found in the MDD group both versus controls and versus the BD group. The effect was specific for the right hemisphere and dorsal AC and was restricted to layer V pyramidal neurons. The results suggest that only patients with MDD display region-specific chronic hypoactivity of these output neurons, which are critical for mood regulation. Furthermore, in our cohort, unipolar and bipolar I depression could be differentiated relative to the presumed AC hypoactivity and psychotropic medication did not counteract the observed effect.