To investigate which biological processes underlie sex-specific changes in OUD, we performed pathway analyses using female-biased and male-biased DEGs. In female individuals with OUD, pathways were primarily associated with the upregulation of DNA repair processes, particularly in MSNs, accompanied by upregulation of interferon response signaling in glial cells, along with the upregulation of synaptic-related functions in astrocytes (Fig. 6b; Supplementary Data 1–S13, S15). We then investigated significant key sex-specific factors in specific cell types of individuals with OUD. We identified the FK506 binding protein 5, FKBP5, as a potential factor in the role for sex in opioid use.
