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- Kaltsouni, Elisavet
(författare)
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Neuroimaging progesterone receptor modulation in patients with premenstrual dysphoric disorder : Is it just in your head?
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Premenstrual dysphoric disorder (PMDD) is a menstrually related mood disorder affecting about 5% of women during their reproductive years. The disorder is cyclic, with the symptomatology namely occurring at the luteal phase of a menstrual cycle, for most ovulatory menstrual cycles and entails a series of mood and physical symptoms. A neural susceptibility to regular hormonal fluctuations is hypothesized as the neuropathophysiological mechanism. While treatment options, such as selective serotonin reuptake inhibitors and hormonal interventions, are available, the neural mechanisms underlying symptom relief remain largely unclear. In this series of studies, a multimodal neuroimaging design was approach was used to reveal the neural correlates of three-month, low-dose selective progesterone receptor modulator (SPRM) treatment in comparison to a placebo. This treatment has been demonstrated to be effective in alleviating psychological symptoms associated with PMDD. Thirty-five women with fulfilling the criteria of a PMDD diagnosis were randomized to treatment with SPRM or placebo, with structural and functional MRI scans conducted before and after randomization. Findings indicated enhanced fronto-cingulate activity during a reactive aggression task in the SPRM treatment group compared to placebo, along with a negative association between aggressive responding and brain activity in the placebo group. Resting state functional connectivity was additionally altered after treatment with SPRM in fronto-visual, temporo-insular, and temporo-cerebellar regions. Additionally, a positive correlation was observed between the reduction in cortisol levels and the decrease in temporo-insular connectivity. No treatment effects were observed on brain structure, including grey and white matter volume, as well as cortical surface architecture. Lastly, White matter microstructure integrity did not differ longitudinally but showed cross-sectional differences. In conclusion, the effects of SPRM treatment were primarily observed in brain function, specifically in terms of enhanced cognitive control processing in the context of reactive aggression and resting state functional connectivity in regions relevant to cognitive and sensorimotor processing, with no significant structural alterations noted. Taken together, these findings confirm that the fluctuations rather than absolute levels of ovarian hormones are primary contributing to premenstrual symptomatology, potentially through hormonal-state dependent functional correlates.
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| 2. |
- Kaltsouni, Elisavet, et al.
(författare)
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White matter volume and treatment with selective progesterone receptor modulator in patients with premenstrual dysphoric disorder
- 2024
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Ingår i: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 163
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Tidskriftsartikel (refereegranskat)abstract
- Premenstrual dysphoric disorder (PMDD) is a mood disorder for which selective progesterone receptor modulator (SPRM) treatment has been demonstrated to be beneficial. The neural signatures of this treatment have been so far identified as greater fronto-cingulate reactivity during aggressive response to provocation, but no changes in terms of gray matter structure. White matter has recently been found to differ between patients with PMDD and healthy controls. The present study thus sought to investigate the relationship between white matter volume and SPRM treatment in patients with PMDD. A pharmaco-neuroimaging study was conducted on patients with PMDD participating in a randomized controlled trial. Participants underwent magnetic resonance imaging before and after treatment randomization to ulipristal acetate (an SPRM), or placebo, for three months. The interaction effect of treatment by time on white matter volume (WMV) was assessed. Voxel based morphometry analyses were performed on both a whole brain exploratory level and on regions of interest. No treatment effect was observed on WMV in any region, including the anterior thalamic radiations, cingulum, forceps minor, fornix, inferior fronto-occipital fasciculus, superior cerebellar peduncle, superior longitudinal fasciculus, and uncinate fasciculus. This is the first finding to indicate that no white matter volume alterations follow three-month progesterone antagonism, suggesting that white matter volume does not participate in symptom relief upon SPRM treatment for PMDD.
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