PMID- 28416813
OWN - NLM
STAT- MEDLINE
DCOM- 20190404
LR  - 20230417
IS  - 1476-5578 (Electronic)
IS  - 1359-4184 (Print)
IS  - 1359-4184 (Linking)
VI  - 23
IP  - 4
DP  - 2018 Apr
TI  - Brain-derived neurotrophic factor Val(66)Met genotype and ovarian steroids 
      interactively modulate working memory-related hippocampal function in women: a 
      multimodal neuroimaging study.
PG  - 1066-1075
LID - 10.1038/mp.2017.72 [doi]
AB  - Preclinical evidence suggests that the actions of ovarian steroid hormones and 
      brain-derived neurotrophic factor (BDNF) are highly convergent on brain function. 
      Studies in humanized mice document an interaction between estrus cycle-related 
      changes in estradiol secretion and BDNF Val(66)Met genotype on measures of 
      hippocampal function and anxiety-like behavior. We believe our multimodal imaging 
      data provide the first demonstration in women that the effects of the BDNF 
      Val/Met polymorphism on hippocampal function are selectively modulated by 
      estradiol. In a 6-month pharmacological hormone manipulation protocol, healthy, 
      regularly menstruating, asymptomatic women completed positron emission tomography 
      (PET) and functional magnetic resonance imaging (fMRI) scans while performing the 
      n-back working memory task during three hormone conditions: ovarian suppression 
      induced by the gonadotropin-releasing hormone agonist, leuprolide acetate; 
      leuprolide plus estradiol; and leuprolide plus progesterone. For each of the 
      three hormone conditions, a discovery data set was obtained with oxygen-15 water 
      regional cerebral blood flow PET in 39 healthy women genotyped for BDNF 
      Val(66)Met, and a confirmatory data set was obtained with fMRI in 27 women. Our 
      results, in close agreement across the two imaging platforms, demonstrate an 
      ovarian hormone-by-BDNF interaction on working memory-related hippocampal 
      function (PET: F(2,37)=9.11, P=0.00026 uncorrected, P=0.05, familywise error 
      corrected with small volume correction; fMRI: F(2,25)=5.43, P=0.01, uncorrected) 
      that reflects differential hippocampal recruitment in Met carriers but only in 
      the presence of estradiol. These findings have clinical relevance for 
      understanding the neurobiological basis of individual differences in the 
      cognitive and behavioral effects of ovarian steroids in women, and may provide a 
      neurogenetic framework for understanding neuropsychiatric disorders related to 
      reproductive hormones as well as illnesses with sex differences in disease 
      expression and course.
FAU - Wei, S-M
AU  - Wei SM
AD  - Section on Integrative Neuroimaging, National Institute of Mental Health 
      Intramural Research Programs, National Institutes of Health, Bethesda, MD, USA.
AD  - Clinical and Translational Neuroscience Branch, National Institute of Mental 
      Health Intramural Research Programs, National Institutes of Health, Bethesda, MD, 
      USA.
FAU - Baller, E B
AU  - Baller EB
AD  - Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
FAU - Kohn, P D
AU  - Kohn PD
AD  - Section on Integrative Neuroimaging, National Institute of Mental Health 
      Intramural Research Programs, National Institutes of Health, Bethesda, MD, USA.
AD  - Clinical and Translational Neuroscience Branch, National Institute of Mental 
      Health Intramural Research Programs, National Institutes of Health, Bethesda, MD, 
      USA.
FAU - Kippenhan, J S
AU  - Kippenhan JS
AD  - Section on Integrative Neuroimaging, National Institute of Mental Health 
      Intramural Research Programs, National Institutes of Health, Bethesda, MD, USA.
AD  - Clinical and Translational Neuroscience Branch, National Institute of Mental 
      Health Intramural Research Programs, National Institutes of Health, Bethesda, MD, 
      USA.
FAU - Kolachana, B
AU  - Kolachana B
AD  - Clinical and Translational Neuroscience Branch, National Institute of Mental 
      Health Intramural Research Programs, National Institutes of Health, Bethesda, MD, 
      USA.
FAU - Soldin, S J
AU  - Soldin SJ
AD  - Department of Laboratory Medicine, Clinical Center, National Institutes of 
      Health, Bethesda, MD, USA.
FAU - Rubinow, D R
AU  - Rubinow DR
AD  - Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel 
      Hill, NC, USA.
FAU - Schmidt, P J
AU  - Schmidt PJ
AD  - Section on Behavioral Endocrinology, National Institute of Mental Health 
      Intramural Research Programs, National Institutes of Health, Bethesda, MD, USA.
FAU - Berman, K F
AU  - Berman KF
AD  - Section on Integrative Neuroimaging, National Institute of Mental Health 
      Intramural Research Programs, National Institutes of Health, Bethesda, MD, USA.
AD  - Clinical and Translational Neuroscience Branch, National Institute of Mental 
      Health Intramural Research Programs, National Institutes of Health, Bethesda, MD, 
      USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT00004571
SI  - ClinicalTrials.gov/NCT00001258
SI  - ClinicalTrials.gov/NCT00001322
GR  - ZIA MH002717/ImNIH/Intramural NIH HHS/United States
GR  - ZIA MH002717/MH/NIMH NIH HHS/United States
GR  - Z01 MH002865/ImNIH/Intramural NIH HHS/United States
GR  - ZIA MH002874/ImNIH/Intramural NIH HHS/United States
GR  - ZIA MH002874/MH/NIMH NIH HHS/United States
GR  - Z01 MH002874/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
DEP - 20170418
PL  - England
TA  - Mol Psychiatry
JT  - Molecular psychiatry
JID - 9607835
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Gonadal Steroid Hormones)
RN  - 0 (Suppositories)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - 4TI98Z838E (Estradiol)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - AE28F7PNPL (Methionine)
RN  - EFY6W0M8TG (Leuprolide)
RN  - HG18B9YRS7 (Valine)
SB  - IM
MH  - Adult
MH  - Brain-Derived Neurotrophic Factor/*genetics/*metabolism
MH  - Cerebrovascular Circulation
MH  - Double-Blind Method
MH  - Estradiol/administration & dosage/blood
MH  - Female
MH  - Gonadal Steroid Hormones/*metabolism
MH  - Hippocampus/diagnostic imaging/*metabolism
MH  - Humans
MH  - Leuprolide/pharmacology
MH  - Magnetic Resonance Imaging
MH  - Memory, Short-Term/*physiology
MH  - Methionine/genetics
MH  - Middle Aged
MH  - Multimodal Imaging/methods
MH  - Neuroimaging/methods
MH  - Neuropsychological Tests
MH  - Ovary/metabolism
MH  - Polymorphism, Single Nucleotide
MH  - Positron-Emission Tomography
MH  - Progesterone/administration & dosage/blood
MH  - Random Allocation
MH  - Suppositories
MH  - Valine/genetics
PMC - PMC10103851
MID - NIHMS1887138
COIS- CONFLICT OF INTEREST The authors declare no conflict of interest.
EDAT- 2017/04/19 06:00
MHDA- 2019/04/05 06:00
PMCR- 2023/04/14
CRDT- 2017/04/19 06:00
PHST- 2016/08/30 00:00 [received]
PHST- 2017/01/25 00:00 [revised]
PHST- 2017/02/15 00:00 [accepted]
PHST- 2017/04/19 06:00 [pubmed]
PHST- 2019/04/05 06:00 [medline]
PHST- 2017/04/19 06:00 [entrez]
PHST- 2023/04/14 00:00 [pmc-release]
AID - mp201772 [pii]
AID - 10.1038/mp.2017.72 [doi]
PST - ppublish
SO  - Mol Psychiatry. 2018 Apr;23(4):1066-1075. doi: 10.1038/mp.2017.72. Epub 2017 Apr 
      18.