Though we did not see any differences in miR-34a expression in PFC nor ACC of BD patients compared to control individuals, we note that a recent study on the PFC from 15 BD patient samples and 15 non-psychiatric controls reported a modest 0.84-fold downregulation of miR-34a in PFC of BD patients relative to controls73, and another study reported no difference74. Such discrepancies in gene expression between post-mortem brain cohorts may be due to disease heterogeneity and possible methodological reasons. Future studies with additional cohorts are needed to replicate our findings and to determine whether miR-34a alterations in BD are widespread in the brain or limited to specific brain regions as we observed. Addressing these questions will benefit from access to high-quality post-mortem brain tissue collections of sizes commensurate with the known phenotypic genetic heterogeneity of the disorder, along with sub-regional and ideally cell subtype specific. Being able to generate defined neuronal subtypes (e.g. cerebellar neurons) with authentic patterning of the human brain, will allow explicit test of the correlation between in vitro cellular models and post-mortem observations, the absence of which is a limitation of our current study.
