经前烦躁障碍患者孕酮拮抗作用下的白质完整性：一项随机安慰剂对照弥散张量成像研究

White matter integrity upon progesterone antagonism in individuals with premenstrual dysphoric disorder: A randomized placebo-controlled diffusion tensor imaging study.

作者信息

Kaltsouni Elisavet, Gu Xuan, Wikström Johan, Hahn Andreas, Lanzenberger Rupert, Sundström-Poromaa Inger, Comasco Erika

机构信息

Department of Women's and Children's Health, Science for Life Laboratory, Uppsala University, Sweden.

Department of Surgical Sciences, Neuroradiology, Uppsala University, Uppsala, Sweden.

出版信息

Prog Neuropsychopharmacol Biol Psychiatry. 2025 Jan 10;136:111179. doi: 10.1016/j.pnpbp.2024.111179. Epub 2024 Oct 23.

DOI:10.1016/j.pnpbp.2024.111179

PMID:39454851

Abstract

BACKGROUND

Premenstrual dysphoric disorder (PMDD) is a depressive disorder triggered by fluctuations of progesterone and estradiol during the luteal phase of the menstrual cycle. Selective progesterone receptor modulation (SPRM), while exerting an antagonistic effect on progesterone and maintaining estradiol on moderate levels, has shown beneficial effects on the mental symptoms of PMDD. Progesterone is also known for its neuroprotective effects, while synthetic progestins have been suggested to promote myelination. However, the impact of SPRM treatment on white matter microstructure is unexplored.

METHODS

Diffusion tensor imaging was employed to collect data on white matter integrity in patients with PMDD, before and after treatment with ulipristal acetate (an SPRM) or placebo, as part of a double-blind randomized controlled-trial. Tract based spatial statistics were performed to investigate SPRM treatment vs. placebo longitudinal effects on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), on the whole white matter skeleton.

RESULTS

Voxel-wise analyses indicated no change over time in any white matter microstructure metrics in individuals treated with SPRM versus placebo. Improvement in PMDD symptoms did not correlate with changes in white matter microstructure. In secondary, exploratory, cross-sectional comparisons during treatment, the SPRM group displayed lower FA and higher MD, RD, and AD than the placebo group in several tracts.

CONCLUSION

The main findings suggest that SPRM treatment did not impact white matter microstructure compared with placebo. However, secondary exploratory analyses yielded between-group differences after treatment, which call for further investigation on the tracts potentially impacted by progesterone antagonism.

CLINICAL TRIAL REGISTRATION

EUDRA-CT 2016-001719-19; "Selective progesterone receptor modulators for treatment of premenstrual dysphoric disorder. A randomized, double-blind, placebo-controlled study."; https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001719-19/SE.

摘要

背景

经前烦躁障碍（PMDD）是一种在月经周期黄体期由孕酮和雌二醇波动引发的抑郁障碍。选择性孕酮受体调节剂（SPRM）在对孕酮发挥拮抗作用并将雌二醇维持在适度水平时，已显示出对PMDD精神症状的有益效果。孕酮还以其神经保护作用而闻名，而合成孕激素则被认为可促进髓鞘形成。然而，SPRM治疗对白质微观结构的影响尚未得到探索。

方法

作为一项双盲随机对照试验的一部分，采用扩散张量成像收集PMDD患者在接受醋酸乌利司他（一种SPRM）或安慰剂治疗前后的白质完整性数据。进行基于体素的空间统计学分析，以研究SPRM治疗与安慰剂对整个白质骨架上的分数各向异性（FA）、平均扩散率（MD）、径向扩散率（RD）和轴向扩散率（AD）的纵向影响。