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Emotion-induced brain activation across the menstrual cycle in individuals with premenstrual dysphoric disorder and associations to serum levels of progesterone-derived neurosteroids
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
Department of Women's and Children's Health, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Department of Women's and Children's Health, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
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2023 (English)In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 13, no 1, article id 124Article in journal (Refereed) Published
Abstract [en]

Premenstrual dysphoric disorder (PMDD) is a debilitating disorder characterized by severe mood symptoms in the luteal phase of the menstrual cycle. PMDD symptoms are hypothesized to be linked to an altered sensitivity to normal luteal phase levels of allopregnanolone (ALLO), a GABAA-modulating progesterone metabolite. Moreover, the endogenous 3β-epimer of ALLO, isoallopregnanolone (ISO), has been shown to alleviate PMDD symptoms through its selective and dose-dependent antagonism of the ALLO effect. There is preliminary evidence showing altered recruitment of brain regions during emotion processing in PMDD, but whether this is associated to serum levels of ALLO, ISO or their relative concentration is unknown. In the present study, subjects with PMDD and asymptomatic controls underwent functional magnetic resonance imaging (fMRI) in the mid-follicular and the late-luteal phase of the menstrual cycle. Brain responses to emotional stimuli were investigated and related to serum levels of ovarian steroids, the neurosteroids ALLO, ISO, and their ratio ISO/ALLO. Participants with PMDD exhibited greater activity in brain regions which are part of emotion-processing networks during the late-luteal phase of the menstrual cycle. Furthermore, activity in key regions of emotion processing networks - the parahippocampal gyrus and amygdala - was differentially associated to the ratio of ISO/ALLO levels in PMDD subjects and controls. Specifically, a positive relationship between ISO/ALLO levels and brain activity was found in PMDD subjects, while the opposite was observed in controls. In conclusion, individuals with PMDD show altered emotion-induced brain responses in the late-luteal phase of the menstrual cycle which may be related to an abnormal response to physiological levels of GABAA-active neurosteroids.

Place, publisher, year, edition, pages
Springer Nature, 2023. Vol. 13, no 1, article id 124
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Psychiatry
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URN: urn:nbn:se:umu:diva-206958DOI: 10.1038/s41398-023-02424-3ISI: 000968319200001PubMedID: 37055419Scopus ID: 2-s2.0-85152386545OAI: oai:DiVA.org:umu-206958DiVA, id: diva2:1753359
Available from: 2023-04-26 Created: 2023-04-26 Last updated: 2024-03-18Bibliographically approved

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Stiernman, LouiseBoraxbekk, Carl-JohanJohansson, Inga-MajBixo, Marie

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