Abstract

Substantial evidence suggests that circulating ovarian steroids modulate behavior differently in women with PMDD than in those without this condition. However, hormonal state-related abnormalities of neural functioning in PMDD remain to be better characterized. In addition, while altered neural function in PMDD likely co-exists with alterations in intrinsic cellular function, such a relationship has not been explored. Here, we investigated the effects of ovarian steroids on basal, resting regional cerebral blood flow (rCBF) in PMDD, and, in an exploratory analysis, we tested whether the rCBF findings were linked to the expression of ESC/E(Z) genes, which form an essential ovarian steroid-regulated gene-silencing complex. Resting rCBF was measured with oxygen-15 water PET (189 PET sessions in 43 healthy women and 20 women with PMDD) during three self-as-own-control conditions: GnRH agonist (Lupron)-induced ovarian suppression, estradiol add-back, and progesterone add-back. ESC/E(Z) gene expression data were obtained from RNA-sequencing of lymphoblastoid cell lines performed in a previous study and were examined in relation to hormone-induced changes in rCBF. In the rCBF PET data, there was a significant diagnosis-by-hormone interaction in the subgenual cingulate (PFDR = 0.05), an important neuroanatomical hub for regulating affective state. Whereas control women showed no hormonally-related changes in resting rCBF, those with PMDD showed decreased resting rCBF during both estradiol (P = 0.02) and progesterone (P = 0.0002) add-back conditions. In addition, in PMDD, ESC/E(Z) gene expression correlated with the change in resting rCBF between Lupron-alone and progesterone conditions (Pearson r = −0.807, P = 0.016). This work offers a formulation of PMDD that integrates behavioral, neural circuit, and cellular mechanisms, and may provide new targets for future therapeutic interventions.

Details

Title
Subgenual cingulate resting regional cerebral blood flow in premenstrual dysphoric disorder: differential regulation by ovarian steroids and preliminary evidence for an association with expression of ESC/E(Z) complex genes
Author
Shau-Ming, Wei 1 ; Baller, Erica B 2   VIAFID ORCID Logo  ; Martinez, Pedro E 3 ; Goff, Allison C 4   VIAFID ORCID Logo  ; Li, Howard J 4 ; Kohn, Philip D 2 ; Shane, Kippenhan J 2 ; Soldin, Steven J 5 ; Rubinow, David R 6 ; Goldman, David 4   VIAFID ORCID Logo  ; Schmidt, Peter J 3 ; Berman, Karen F 2 

1  Clinical and Translational Neuroscience Branch, NIMH IRP, NIH, Section on Integrative Neuroimaging, Bethesda, USA (GRID:grid.420086.8) (ISNI:0000 0001 2237 2479); Behavioral Endocrinology Branch; NIMH IRP, NIH, Bethesda, USA (GRID:grid.420086.8) (ISNI:0000 0001 2237 2479) 
2  Clinical and Translational Neuroscience Branch, NIMH IRP, NIH, Section on Integrative Neuroimaging, Bethesda, USA (GRID:grid.420086.8) (ISNI:0000 0001 2237 2479) 
3  Behavioral Endocrinology Branch; NIMH IRP, NIH, Bethesda, USA (GRID:grid.420086.8) (ISNI:0000 0001 2237 2479) 
4  Laboratory of Neurogenetics, NIAAA, Bethesda, USA (GRID:grid.420085.b) (ISNI:0000 0004 0481 4802) 
5  NIH Clinical Center, Department of Laboratory Medicine, Bethesda, USA (GRID:grid.410305.3) (ISNI:0000 0001 2194 5650) 
6  University of North Carolina, Department of Psychiatry, Chapel Hill, USA (GRID:grid.410711.2) (ISNI:0000 0001 1034 1720) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
21583188
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41398-021-01328-4
ProQuest document ID
2509905468
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.