PMID- 30356121
OWN - NLM
STAT- MEDLINE
DCOM- 20210114
LR  - 20220420
IS  - 1476-5578 (Electronic)
IS  - 1359-4184 (Print)
IS  - 1359-4184 (Linking)
VI  - 25
IP  - 3
DP  - 2020 Mar
TI  - Epigenetic intersection of BDNF Val66Met genotype with premenstrual dysphoric 
      disorder transcriptome in a cross-species model of estradiol add-back.
PG  - 572-583
LID - 10.1038/s41380-018-0274-3 [doi]
AB  - Premenstrual dysphoric disorder (PMDD) affects over 5% of women, with symptoms 
      similar to anxiety and major depression, and is associated with differential 
      sensitivity to circulating ovarian hormones. Little is known about the genetic 
      and epigenetic factors that increase the risk to develop PMDD. We report that 
      17beta-estradiol (E2) affects the behavior and the epigenome in a mouse model 
      carrying a single-nucleotide polymorphism of the brain-derived neurotrophic 
      factor gene (BDNF Val66Met), in a way that recapitulates the hallmarks of PMDD. 
      Ovariectomized mice heterozygous for the BDNF Met allele (Het-Met) and their 
      matched wild-type (WT) mice were administered estradiol or vehicle in drinking 
      water for 6 weeks. Using the open field and the splash test, we show that E2 
      add-back induces anxiety-like and depression-like behavior in Het-Met mice, but 
      not in WT mice. RNA-seq of the ventral hippocampus (vHpc) highlights that 
      E2-dependent gene expression is markedly different between WT mice and Het-Met 
      mice. Through a comparative whole-genome RNA-seq analysis between mouse vHpc and 
      lymphoblastoid cell line cultures from control women and women with PMDD, we 
      discovered common epigenetic biomarkers that transcend species and cell types. 
      Those genes include epigenetic modifiers of the ESC/E(Z) complex, an effector of 
      response to ovarian steroids. Although the BDNF Met genotype intersects the 
      behavioral and transcriptional traits of women with PMDD, we suggest that these 
      similarities speak to the epigenetic factors by which ovarian steroids produce 
      negative behavioral effects.
FAU - Marrocco, Jordan
AU  - Marrocco J
AD  - Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, USA.
FAU - Einhorn, Nathan R
AU  - Einhorn NR
AD  - Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, USA.
FAU - Petty, Gordon H
AU  - Petty GH
AD  - Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, USA.
FAU - Li, Howard
AU  - Li H
AD  - Behavioral Endocrinology Branch, National Institute of Mental Health, Bethesda, 
      MD, USA.
FAU - Dubey, Neelima
AU  - Dubey N
AD  - Dr. D. Y. Patil Biotechnology & Bioinformatics Institute, Pune, India.
FAU - Hoffman, Jessica
AU  - Hoffman J
AD  - Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
FAU - Berman, Karen F
AU  - Berman KF
AD  - Section on Integrative Neuroimaging, National Institute of Mental Health, 
      Bethesda, MD, USA.
FAU - Goldman, David
AU  - Goldman D
AD  - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, 
      Bethesda, MD, USA.
FAU - Lee, Francis S
AU  - Lee FS
AD  - Department of Psychiatry, Sackler Institute for Developmental Psychobiology, 
      Weill Cornell Medical College, New York, NY, USA.
FAU - Schmidt, Peter J
AU  - Schmidt PJ
AD  - Behavioral Endocrinology Branch, National Institute of Mental Health, Bethesda, 
      MD, USA.
FAU - McEwen, Bruce S
AU  - McEwen BS
AD  - Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, USA. 
      mcewen@rockefeller.edu.
LA  - eng
GR  - K24 AA000301/AA/NIAAA NIH HHS/United States
GR  - Z01 AA000301/ImNIH/Intramural NIH HHS/United States
GR  - Z01 MH002865/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20181024
PL  - England
TA  - Mol Psychiatry
JT  - Molecular psychiatry
JID - 9607835
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Estrogens)
RN  - 4TI98Z838E (Estradiol)
RN  - 7171WSG8A2 (BDNF protein, human)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Anxiety/genetics
MH  - Brain-Derived Neurotrophic Factor/*genetics/metabolism
MH  - Epigenesis, Genetic/genetics
MH  - Epigenomics/methods
MH  - Estradiol/pharmacology
MH  - Estrogens
MH  - Female
MH  - Gene Expression Profiling/methods
MH  - Gene Knock-In Techniques
MH  - Genotype
MH  - Hippocampus/metabolism
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Ovary/metabolism
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Premenstrual Dysphoric Disorder/*drug therapy/*genetics/physiopathology
MH  - Transcriptome/genetics
PMC - PMC7042769
COIS- The authors declare that they have no conflict of interest.
EDAT- 2018/10/26 06:00
MHDA- 2021/01/15 06:00
PMCR- 2018/10/24
CRDT- 2018/10/26 06:00
PHST- 2018/05/22 00:00 [received]
PHST- 2018/09/11 00:00 [accepted]
PHST- 2018/10/26 06:00 [pubmed]
PHST- 2021/01/15 06:00 [medline]
PHST- 2018/10/26 06:00 [entrez]
PHST- 2018/10/24 00:00 [pmc-release]
AID - 10.1038/s41380-018-0274-3 [pii]
AID - 274 [pii]
AID - 10.1038/s41380-018-0274-3 [doi]
PST - ppublish
SO  - Mol Psychiatry. 2020 Mar;25(3):572-583. doi: 10.1038/s41380-018-0274-3. Epub 2018 
      Oct 24.