氯胺酮和拉莫三嗪在负面情绪处理过程中的功能活动和连接特征:一项双盲随机对照 fMRI 研究。

IF 5.8 1区 医学 Q1 PSYCHIATRY Translational Psychiatry Pub Date : 2024-10-14 DOI:10.1038/s41398-024-03120-6
Marvin S Meiering, David Weigner, Matti Gärtner, Luisa Carstens, Christian Keicher, Rita Hertrampf, Christian F Beckmann, Maarten Mennes, Andreas Wunder, Anne Weigand, Simone Grimm
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引用次数: 0

摘要

氯胺酮是一种高效抗抑郁药(AD),它以谷氨酸能系统为靶点,在负面情绪处理过程中对大脑回路产生深远影响。有趣的是,氯胺酮对大脑测量的影响对拉莫三嗪的预处理调节很敏感,而拉莫三嗪能抑制谷氨酸的释放。通过研究氯胺酮和拉莫三嗪对谷氨酸传递的拮抗作用,有望发现氯胺酮通过谷氨酸能系统变化介导的作用。因此,研究氯胺酮在负面情绪处理过程中对功能活动和连接性的急性和持续影响时的这种调节作用,将能提供新的见解。在一项双盲、单剂量、随机、安慰剂对照、平行组研究中,75 名健康受试者接受了三种治疗条件(氯胺酮、拉莫三嗪预处理、安慰剂)的调查。受试者在氯胺酮输注期间和24小时后完成一项情绪面孔观察任务。在负性情绪处理过程中,急性氯胺酮给药降低了海马和默认模式网络(DMN)的活动,增加了前边缘耦合。此外,虽然拉莫三嗪能消除氯胺酮引起的功能连接性增加,但它对活动没有急性影响。氯胺酮的持续影响(24 小时后)只体现在功能活动上,后部 DMN 的功能活动显著减少。这种效应在使用拉莫三嗪进行预处理后被阻断。我们的研究结果表明,氯胺酮导致的前边缘耦合的急性增加和DMN后部活动的延迟减少,而不是边缘和DMN招募的减弱,是由谷氨酸能传递的改变介导的。
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Functional activity and connectivity signatures of ketamine and lamotrigine during negative emotional processing: a double-blind randomized controlled fMRI study.

Ketamine is a highly effective antidepressant (AD) that targets the glutamatergic system and exerts profound effects on brain circuits during negative emotional processing. Interestingly, the effects of ketamine on brain measures are sensitive to modulation by pretreatment with lamotrigine, which inhibits glutamate release. Examining the antagonistic effects of ketamine and lamotrigine on glutamate transmission holds promise to identify effects of ketamine that are mediated through changes in the glutamatergic system. Investigating this modulation in relation to both the acute and sustained effects of ketamine on functional activity and connectivity during negative emotional processing should therefore provide novel insights. 75 healthy subjects were investigated in a double-blind, single-dose, randomized, placebo-controlled, parallel-group study with three treatment conditions (ketamine, lamotrigine pre-treatment, placebo). Participants completed an emotional face viewing task during ketamine infusion and 24 h later. Acute ketamine administration decreased hippocampal and Default Mode Network (DMN) activity and increased fronto-limbic coupling during negative emotional processing. Furthermore, while lamotrigine abolished the ketamine-induced increase in functional connectivity, it had no acute effect on activity. Sustained (24 h later) effects of ketamine were only found for functional activity, with a significant reduction in the posterior DMN. This effect was blocked by pretreatment with lamotrigine. Our results suggest that both the acute increases in fronto-limbic coupling and the delayed decrease in posterior DMN activity, but not the attenuated limbic and DMN recruitment after ketamine, are mediated by altered glutamatergic transmission.

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来源期刊
CiteScore
11.50
自引率
2.90%
发文量
484
审稿时长
23 weeks
期刊介绍: Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.
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