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Chunk #39 — Discussion

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Transcriptome alterations are enriched for synapse-associated genes in the striatum of subjects with obsessive-compulsive disorder.
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DEG in the OFC alone. Notably, on a gene-by-gene basis, the normalized qPCR expression from36 and the RNAseq gene expression levels reported here were significantly positively correlated as expected (r = 0.340, p < 0.0001, Table S11). It is therefore likely that there are changes in transcript levels in the OFC of our OCD subjects relative to unaffected comparison subjects, but our small sample size and multiple comparison correction limited our ability to detect them. This interpretation is bolstered by our global analysis demonstrating many more significant differentially expressed transcripts in the global condition (OFC and striatum) than in the striatum alone. Fourth, using the metric of cell type fractions, we cannot currently distinguish changes in cellular and anatomical structure (e.g., reduced medium spiny neuron number) from reductions in synaptic transcripts expressed within those cells. Future experiments will seek to differentiate these possibilities. Despite these limitations, the utility of performing unbiased transcriptomic analysis is clear as it provides a more complete picture of dysfunction across regions and allows for the identification of novel transcripts and signaling pathways that would not otherwise be detected. Furthermore, we demonstrate striking consistency with a previous RNA-sequencing study in disrupted molecular pathways and specific striatal