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Estradiol modulates resting-state connectivity in perimenopausal depression.
- Source :
-
Journal of affective disorders [J Affect Disord] 2025 Feb 15; Vol. 371, pp. 253-260. Date of Electronic Publication: 2024 Nov 22. - Publication Year :
- 2025
-
Abstract
- The perimenopausal transition is marked by an increased risk for affective dysregulation and major depressive disorder (MDD), with hormone replacement therapy using estradiol (E2) showing promise for alleviating symptoms of perimenopausal-onset MDD (PO-MDD). Although E2's effectiveness is recognized, its mechanisms underlying mood symptom modulation remain to be fully elucidated. Building on previous research suggesting that E2 may influence mood by altering cortico-subcortical connectivity, this study investigated the effects of transdermal E2 on resting-state functional connectivity (rsFC) in perimenopausal women with and without PO-MDD, focusing on rsFC changes using seed regions within reward and emotion processing networks. In this pharmaco-fMRI study, 16 participants with PO-MDD and 18 controls underwent rsFC analysis before and after three weeks of transdermal E2 administration. Pre-E2 results showed that the PO-MDD group, compared to controls, exhibited increased connectivity between the right amygdala (seed) and medial prefrontal cortex and anterior cingulate cortex, and decreased connectivity with the supplementary motor area. Comparing groups on change from pre-E2 to post-E2 revealed several significant E2-induced changes in connectivity between the PO-MDD and control groups: PO-MDD showed increased connectivity between the right caudate nucleus (seed) and left insula, and decreased connectivity between the right putamen (seed) and left hippocampus, and the right amygdala (seed) and left ventromedial prefrontal cortex. Notably, changes in connectivity were predictive of symptom trajectories across anhedonia, depressive mood, somatic, and vasomotor domains in the PO-MDD group. These findings enrich our understanding of PO-MDD by highlighting distinct rsFC patterns characteristic of the disorder and their shifts in response to E2 treatment, suggesting potential neural mechanisms underlying E2's mood-modulating effects.<br />Competing Interests: Declaration of competing interest The authors declare no competing interests.<br /> (Published by Elsevier B.V.)
- Subjects :
- Humans
Female
Middle Aged
Gyrus Cinguli physiopathology
Gyrus Cinguli drug effects
Gyrus Cinguli diagnostic imaging
Adult
Putamen physiopathology
Putamen drug effects
Putamen diagnostic imaging
Caudate Nucleus physiopathology
Caudate Nucleus drug effects
Caudate Nucleus diagnostic imaging
Reward
Administration, Cutaneous
Brain drug effects
Brain physiopathology
Brain diagnostic imaging
Perimenopause drug effects
Perimenopause physiology
Estradiol pharmacology
Magnetic Resonance Imaging
Depressive Disorder, Major physiopathology
Depressive Disorder, Major drug therapy
Amygdala physiopathology
Amygdala drug effects
Amygdala diagnostic imaging
Prefrontal Cortex physiopathology
Prefrontal Cortex drug effects
Prefrontal Cortex diagnostic imaging
Subjects
Details
- Language :
- English
- ISSN :
- 1573-2517
- Volume :
- 371
- Database :
- MEDLINE
- Journal :
- Journal of affective disorders
- Publication Type :
- Academic Journal
- Accession number :
- 39581384
- Full Text :
- https://doi.org/10.1016/j.jad.2024.11.068