Brexanolone, a formulation of the
neurosteroid allopregnanolone (ALLO), is approved for treating
postpartum depression (
PPD) and is being investigated for therapeutic efficacy across numerous neuropsychiatric disorders. Given ALLO's beneficial effects on mood in women with
PPD compared to healthy control women, we sought to characterize and compare the cellular response to ALLO in women with (n = 9) or without (n = 10, i.e., Controls) past
PPD, utilizing our previously established patient-derived lymphoblastoid cell lines (LCLs). To mimic in vivo
PPD ALLO-treatment, LCLs were exposed to ALLO or
DMSO vehicle for 60 h and
RNA-sequenced to detect differentially expressed genes (DEGs, pnominal < 0.05). Between ALLO-treated Control and
PPD LCLs, 269 DEGs were identified, including
Glutamate Decarboxylase 1 (GAD1), which was decreased 2-fold in
PPD. Network analysis of
PPD:ALLO DEGs revealed enriched terms related to synaptic activity and
cholesterol biosynthesis. Within-diagnosis analyses (i.e.,
DMSO vs. ALLO) detected 265 ALLO-induced DEGs in Control LCLs compared to only 98 within
PPD LCLs, with just 11 DEGs overlapping. Likewise, the gene ontologies underlying ALLO-induced DEGs in
PPD and Control LCLs were divergent. These data suggest that ALLO may activate unique and opposing molecular pathways in women with
PPD, which may be tied to its
antidepressant mechanism.