重度抑郁症患者度洛西汀治疗后脑去甲肾上腺素转运体有效性变化的纵向PET研究。

IF 3.7 2区 医学 Q1 CLINICAL NEUROLOGY
Sho Moriguchi, Keisuke Takahata, Harumasa Takano, Hironobu Endo, Kenji Tagai, Soichiro Kitamura, Hiroyuki Uchida, Masaru Mimura, Manabu Kubota, Ming-Rong Zhang, Makoto Higuchi
{"title":"重度抑郁症患者度洛西汀治疗后脑去甲肾上腺素转运体有效性变化的纵向PET研究。","authors":"Sho Moriguchi, Keisuke Takahata, Harumasa Takano, Hironobu Endo, Kenji Tagai, Soichiro Kitamura, Hiroyuki Uchida, Masaru Mimura, Manabu Kubota, Ming-Rong Zhang, Makoto Higuchi","doi":"10.1093/ijnp/pyaf064","DOIUrl":null,"url":null,"abstract":"<p><strong>Importance: </strong>The norepinephrine transporter (NET) plays a crucial role in major depressive disorder (MDD). Serotonin and norepinephrine reuptake inhibitors, such as duloxetine, are first-line treatments for MDD. Duloxetine inhibits the reuptake of both serotonin and norepinephrine. However, its precise mechanism, particularly regarding NET occupancy and changes in transporter availability, remains unclear. Norepinephrine transmission, mediated by NET, may be instrumental in treating MDD. Therefore, NET occupancy could serve as a potential biomarker to evaluate treatment efficacy.</p><p><strong>Objective: </strong>This study evaluated duloxetine's impact on brain NET availability in patients with MDD using positron emission tomography (PET) with (S,S)-[18F]FMeNER-D2 and its correlation with clinical symptoms using the Hamilton Depression Rating Scale (HAM-D).</p><p><strong>Design: </strong>Longitudinal study.</p><p><strong>Setting: </strong>Psychiatric hospitals and clinics.</p><p><strong>Participants: </strong>Fifteen patients with MDD.</p><p><strong>Interventions: </strong>Duloxetine (20-60 mg daily).</p><p><strong>Main outcomes and measures: </strong>Baseline PET examinations were conducted for all patients, followed by treatment with duloxetine (20-60 mg daily). After 4-6 weeks of duloxetine administration, a second PET examination was performed, and plasma concentrations of duloxetine were measured immediately before and after the second examination using gas chromatography-mass spectrometry. Seven patients showing symptom improvement over the course of time discontinued duloxetine and underwent a third PET examination after a 2-month washout period.</p><p><strong>Results: </strong>Norepinephrine transporter occupancy by duloxetine was 30%-40% across the doses studied. A paired t-test comparing NET availability before and after duloxetine treatment showed no significant differences, suggesting that duloxetine did not significantly alter NET availability in the short term. Further analysis revealed a significant positive correlation between the change in NET availability and HAM-D scores after treatment. Patients with greater reductions in HAM-D scores exhibited more pronounced reductions in NET availability.</p><p><strong>Conclusions: </strong>These findings underscore the potential role of NET occupancy by duloxetine in the treatment of MDD and its relationship with clinical outcomes.</p><p><strong>Relevance: </strong>Understanding changes in NET and their implications enhances our comprehension of the complex mechanisms behind antidepressants and may reveal new therapeutic targets for MDD and other neuropsychiatric disorders.</p><p><strong>Clinical trial registration number: </strong>UMIN000008251.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":"28 10","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12489337/pdf/","citationCount":"0","resultStr":"{\"title\":\"A longitudinal PET study on changes in brain norepinephrine transporter availability following duloxetine treatment in major depressive disorder.\",\"authors\":\"Sho Moriguchi, Keisuke Takahata, Harumasa Takano, Hironobu Endo, Kenji Tagai, Soichiro Kitamura, Hiroyuki Uchida, Masaru Mimura, Manabu Kubota, Ming-Rong Zhang, Makoto Higuchi\",\"doi\":\"10.1093/ijnp/pyaf064\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Importance: </strong>The norepinephrine transporter (NET) plays a crucial role in major depressive disorder (MDD). Serotonin and norepinephrine reuptake inhibitors, such as duloxetine, are first-line treatments for MDD. Duloxetine inhibits the reuptake of both serotonin and norepinephrine. However, its precise mechanism, particularly regarding NET occupancy and changes in transporter availability, remains unclear. Norepinephrine transmission, mediated by NET, may be instrumental in treating MDD. Therefore, NET occupancy could serve as a potential biomarker to evaluate treatment efficacy.</p><p><strong>Objective: </strong>This study evaluated duloxetine's impact on brain NET availability in patients with MDD using positron emission tomography (PET) with (S,S)-[18F]FMeNER-D2 and its correlation with clinical symptoms using the Hamilton Depression Rating Scale (HAM-D).</p><p><strong>Design: </strong>Longitudinal study.</p><p><strong>Setting: </strong>Psychiatric hospitals and clinics.</p><p><strong>Participants: </strong>Fifteen patients with MDD.</p><p><strong>Interventions: </strong>Duloxetine (20-60 mg daily).</p><p><strong>Main outcomes and measures: </strong>Baseline PET examinations were conducted for all patients, followed by treatment with duloxetine (20-60 mg daily). After 4-6 weeks of duloxetine administration, a second PET examination was performed, and plasma concentrations of duloxetine were measured immediately before and after the second examination using gas chromatography-mass spectrometry. Seven patients showing symptom improvement over the course of time discontinued duloxetine and underwent a third PET examination after a 2-month washout period.</p><p><strong>Results: </strong>Norepinephrine transporter occupancy by duloxetine was 30%-40% across the doses studied. A paired t-test comparing NET availability before and after duloxetine treatment showed no significant differences, suggesting that duloxetine did not significantly alter NET availability in the short term. Further analysis revealed a significant positive correlation between the change in NET availability and HAM-D scores after treatment. Patients with greater reductions in HAM-D scores exhibited more pronounced reductions in NET availability.</p><p><strong>Conclusions: </strong>These findings underscore the potential role of NET occupancy by duloxetine in the treatment of MDD and its relationship with clinical outcomes.</p><p><strong>Relevance: </strong>Understanding changes in NET and their implications enhances our comprehension of the complex mechanisms behind antidepressants and may reveal new therapeutic targets for MDD and other neuropsychiatric disorders.</p><p><strong>Clinical trial registration number: </strong>UMIN000008251.</p>\",\"PeriodicalId\":14134,\"journal\":{\"name\":\"International Journal of Neuropsychopharmacology\",\"volume\":\"28 10\",\"pages\":\"\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2025-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12489337/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Neuropsychopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/ijnp/pyaf064\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Neuropsychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/ijnp/pyaf064","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0

摘要

重要性:去甲肾上腺素转运蛋白(NET)在重度抑郁症(MDD)中起着至关重要的作用。血清素和去甲肾上腺素再摄取抑制剂,如度洛西汀,是重度抑郁症的一线治疗药物。度洛西汀抑制血清素和去甲肾上腺素的再摄取。然而,其确切的机制,特别是关于净占用和转运体可用性的变化,仍然不清楚。NET介导的去甲肾上腺素传递可能有助于治疗重度抑郁症。因此,NET占用率可以作为评价治疗效果的潜在生物标志物。目的:本研究利用正电子发射断层扫描(PET)和(S,S)-[18F]FMeNER-D2评估度洛西汀对重度抑郁症患者脑NET可用性的影响,并利用汉密尔顿抑郁评定量表(HAM-D)评估度洛西汀与临床症状的相关性。设计:纵向研究。环境:精神病院和诊所。参与者:15例重度抑郁症患者。干预措施:度洛西汀(每天20-60毫克)。主要结局和措施:所有患者进行基线PET检查,随后给予度洛西汀(20- 60mg /天)治疗。在给予度洛西汀4-6周后,进行第二次PET检查,并在第二次检查前后立即使用气相色谱-质谱法测量度洛西汀的血浆浓度。7名症状改善的患者停用度洛西汀,并在2个月的洗脱期后进行了第三次PET检查。结果:在研究的剂量范围内,度洛西汀对去甲肾上腺素转运体的占用率为30%-40%。配对t检验比较度洛西汀治疗前后的NET可用性没有显著差异,表明度洛西汀短期内没有显著改变NET可用性。进一步分析显示,治疗后NET可用性的变化与HAM-D评分之间存在显著的正相关。HAM-D评分下降更大的患者表现出更明显的NET可用性下降。结论:这些发现强调了度洛西汀在治疗重度抑郁症中的潜在作用及其与临床结果的关系。相关性:了解NET的变化及其含义可以增强我们对抗抑郁药物背后复杂机制的理解,并可能揭示重度抑郁症和其他神经精神疾病的新治疗靶点。临床试验注册号:UMIN000008251。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A longitudinal PET study on changes in brain norepinephrine transporter availability following duloxetine treatment in major depressive disorder.

Importance: The norepinephrine transporter (NET) plays a crucial role in major depressive disorder (MDD). Serotonin and norepinephrine reuptake inhibitors, such as duloxetine, are first-line treatments for MDD. Duloxetine inhibits the reuptake of both serotonin and norepinephrine. However, its precise mechanism, particularly regarding NET occupancy and changes in transporter availability, remains unclear. Norepinephrine transmission, mediated by NET, may be instrumental in treating MDD. Therefore, NET occupancy could serve as a potential biomarker to evaluate treatment efficacy.

Objective: This study evaluated duloxetine's impact on brain NET availability in patients with MDD using positron emission tomography (PET) with (S,S)-[18F]FMeNER-D2 and its correlation with clinical symptoms using the Hamilton Depression Rating Scale (HAM-D).

Design: Longitudinal study.

Setting: Psychiatric hospitals and clinics.

Participants: Fifteen patients with MDD.

Interventions: Duloxetine (20-60 mg daily).

Main outcomes and measures: Baseline PET examinations were conducted for all patients, followed by treatment with duloxetine (20-60 mg daily). After 4-6 weeks of duloxetine administration, a second PET examination was performed, and plasma concentrations of duloxetine were measured immediately before and after the second examination using gas chromatography-mass spectrometry. Seven patients showing symptom improvement over the course of time discontinued duloxetine and underwent a third PET examination after a 2-month washout period.

Results: Norepinephrine transporter occupancy by duloxetine was 30%-40% across the doses studied. A paired t-test comparing NET availability before and after duloxetine treatment showed no significant differences, suggesting that duloxetine did not significantly alter NET availability in the short term. Further analysis revealed a significant positive correlation between the change in NET availability and HAM-D scores after treatment. Patients with greater reductions in HAM-D scores exhibited more pronounced reductions in NET availability.

Conclusions: These findings underscore the potential role of NET occupancy by duloxetine in the treatment of MDD and its relationship with clinical outcomes.

Relevance: Understanding changes in NET and their implications enhances our comprehension of the complex mechanisms behind antidepressants and may reveal new therapeutic targets for MDD and other neuropsychiatric disorders.

Clinical trial registration number: UMIN000008251.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
8.40
自引率
2.10%
发文量
230
审稿时长
4-8 weeks
期刊介绍: The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信