Gene Expression between PMD and Control LCLs at Baseline, E2, and E2 Withdrawal

In this study, lymphoblastoid cell lines (LCLs) derived from women with past perimenopausal depression (PMD) (n = 8) and asymptomatic controls (n = 9) were compared via poly(A)-selected transcriptome sequencing (RNA-seq). LCLs were cultured in three experimental conditions: at vehicle baseline (ovarian steroid-free), during estradiol (E2) treatment, and following E2-withdrawal. Transcriptomic analysis revealed significant differences in transcript expression in PMD LCLs compared to controls in all experimental conditions, and significant overlap in genes that were changed in PMD regardless of experimental condition. Among these, chemokine CXCL10 was upregulated in women with PMD, but most so after E2-WD and CYP7B1, an enzyme intrinsic to DHEA metabolism, was upregulated in PMD across experimental conditions. Finally, this in vitro model identified gene networks dysregulated in PMD which included inflammatory response, early/late E2-response, and cholesterol homeostasis. Data available will include the normalized counts for each subject in the study.
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The NIH IRB approved the study protocol, and all women provided written informed consent. Women were aged 45 to 65 years, postmenopausal, and in good health; none had current clinically significant mood symptoms. We recruited women with past perimenopausal depression who reported a history of major or minor depression at midlife in association with menstrual cycle irregularity, with remission of this depression after HT (i.e., "past PMD") and matched asymptomatic women who were either currently receiving HT or had previously received HT and who had no past depression (i.e., controls). Within the 8 women with past PMD in the RNA-seq cohort, 6 experienced a past major depressive episode, and 2 experienced a past minor depressive episode during the perimenopause. The asymptomatic control group consisted of women without PMD based on absence of symptoms throughout the same protocol. There were no significant differences in age, STRAW Stage, ethnicity, and years since last menstrual period of the women the RNA-seq LCLs were derived from (at the time of the clinical study). ]]>