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Chunk #30 — 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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Compared to synaptic enrichment (cluster 1), which included mostly downregulated DEG, cluster 4 pathways associated with circulatory and cardiovascular system development, transmembrane tyrosine kinase activity (RTK), and components of the plasma membrane, mostly consisted of upregulated DEG (Table S3). These upregulated gene sets are consistent with the increased vascular cell expression profile observed in our cell type deconvolution (Fig. 3A), and increased angiogenesis in these regions may play a role in the elevated blood-oxygen level dependent (BOLD) signal observed in functional imaging studies of OCD subjects. While previous studies of RTK alterations in OCD have identified an association between tropomyosin receptor kinase B/neurotrophic tyrosine kinase receptor type 2 (TRKB/NTRK2) and OCD54, our data suggest a role for other kinases, including Janus kinase 3 (JAK3) and protein kinase C beta (PRKCB1), though their precise functions remain to be determined.