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

IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Progress in Neuro-Psychopharmacology & Biological Psychiatry Pub Date : 2024-10-23 DOI:10.1016/j.pnpbp.2024.111179
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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
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黄体酮拮抗剂对经前性欲障碍患者白质完整性的影响:随机安慰剂对照弥散张量成像研究。
背景:经前期情感障碍(PMDD)是一种由月经周期黄体期的孕酮和雌二醇波动引发的抑郁障碍。选择性黄体酮受体调节(SPRM)可对黄体酮产生拮抗作用,并将雌二醇维持在适度水平,从而对 PMDD 的精神症状产生有益影响。孕酮还具有神经保护作用,而合成孕激素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研究:方法:在一项双盲随机对照试验中,采用弥散张量成像技术收集了PMDD患者在接受醋酸乌利司他(一种SPRM)或安慰剂治疗前后白质完整性的数据。对整个白质骨架上的分数各向异性(FA)、平均弥散度(MD)、径向弥散度(RD)和轴向弥散度(AD)进行了基于簇的空间统计,以研究 SPRM 治疗与安慰剂的纵向影响:结果:体素分析表明,接受SPRM治疗的患者与接受安慰剂治疗的患者相比,其白质微观结构指标随时间的推移均无变化。PMDD 症状的改善与白质微结构的变化无关。在治疗期间进行的次要、探索性横断面比较中,SPRM组在几个束中显示出较低的FA和较高的MD、RD和AD:主要研究结果表明,与安慰剂相比,SPRM 治疗不会影响白质微观结构。然而,次要探索性分析得出了治疗后的组间差异,这要求进一步研究可能受孕酮拮抗作用影响的束:临床试验注册:EUDRA-CT 2016-001719-19;"选择性孕酮受体调节剂治疗经前期情感障碍。随机、双盲、安慰剂对照研究";https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001719-19/SE。
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来源期刊
CiteScore
12.00
自引率
1.80%
发文量
153
审稿时长
56 days
期刊介绍: Progress in Neuro-Psychopharmacology & Biological Psychiatry is an international and multidisciplinary journal which aims to ensure the rapid publication of authoritative reviews and research papers dealing with experimental and clinical aspects of neuro-psychopharmacology and biological psychiatry. Issues of the journal are regularly devoted wholly in or in part to a topical subject. Progress in Neuro-Psychopharmacology & Biological Psychiatry does not publish work on the actions of biological extracts unless the pharmacological active molecular substrate and/or specific receptor binding properties of the extract compounds are elucidated.
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