Whole transcriptome expression profiles in lymphoblastoid cells from women with PMDD and controls: diagnostic differences and differential response to ovarian steroids

Tuesday, September 23, 2014 — Poster Session III
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NIMH	CLIN-8

Authors

• J.F. Hoffman
• N. Dubey
• K. Schuebel
• C. Marietta
• Q. Yuan
• P.E. Martinez
• L.K. Nieman
• D.R. Rubinow
• P.J. Schmidt
• D. Goldman

Abstract

Premenstrual dysphoric disorder (PMDD) is a mood disorder linked with the menstrual cycle. A lack of consistent diagnosis-related differences in reproductive hormones, remission of symptoms during suppression of ovarian steroid secretion, and recurrence after re-exposure to physiologic levels of steroids in women with PMDD suggests the behavioral differences reflect an abnormal cellular response to ovarian steroids. We used lymphoblastoid cell cultures from women who underwent a hormonal intervention paradigm and confirmed presence (PMDD) or absence (asymptomatic controls) of an ovarian-triggered mood disorder. Cells were exposed to vehicle or steroids (estradiol or progesterone) and examined for changes in gene expression and protein levels. Whole transcriptome RNA analysis revealed genome-wide RNA expression changes between women with PMDD and asymptomatic controls, as well as several molecular pathways that appear to be altered in women with PMDD. We found significant effects of diagnosis (MTF2, PHF19, SIRT1, p<0.05) and diagnosis x treatment interactions (EED, EZH2, MTF2, p<0.05) in several genes from the ESC/E(z) complex, which is a known modulator of steroid signaling and involved in gene silencing. These data could identify the cellular basis for the differential behavioral sensitivity observed in PMDD and other reproductive endocrine-related depressions.

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