Rebuilding the atrophied brain: 6-month nasal esketamine therapy expands key frontal and hippocampal regions and reduces serum neurofilament levels in patients with major depressive disorder. A proof-of-concept study of the depTesk (DEPression treatment with ESKetamine) study.

IF 4.6 3区 医学 Q2 CLINICAL NEUROLOGY
Ana Rodríguez Lorente, María Pilar Campos-Navarro, Ángela Gil Montoya, Celia Marín Pérez, María Luisa Maso Navarro, Tomás Orgaz Morales, Nuria López Ramirez, Juan Antonio García-Carmona
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Abstract

Objectives: This proof-of-concept study aimed to assess the impact of intranasal esketamine (ESK-IN) in brain volume and neurofilament light chain (sNfL) over 6-months in patients with treatment resistant depression (TDR).

Methods: Seven TRD patients received ESK-IN while continuing oral antidepressants. Clinical evaluations were conducted at baseline, 1, 3, and 6 months, with MRI scans and blood samples taken at baseline and 6 months. Brain volume was assessed using VolBrain2 and DSI studio.

Results: Compared to controls, TRD patients initially showed lower volumes (mm3) in key cortical regions such as the insula (p = 0.0156), the frontal lobe (p = 0.0228) the superior parietal lobe (p = 0.0402), both superior (p = 0.0216) and inferior (p = 0.0437) temporal lobes and subcortical regions such as the nucleus accumbens (p = 0.0056), putamen (p = 0.0083), thalamus (p = 0.0102) and the hippocampus (p = 0.0001). Brain volume increased in the frontal cortex (p = 0.0295), the anterior cingulate (p = 0.0496), and hippocampus (p = 0.0015), as well as in the volume and fiber tracts associated with emotional regulation, such as the frontoparahippocampal (p = 0.0156 and p = 0.0313, respectively), the frontoparietal (p = 0.0496 and p = 0.0156, respectively) and the frontal aslant tract after 6 months on treatment with ESK-IN. In parallel, sNfL levels decreased post-treatment, indicating potential neuroprotective effects.

Conclusions: ESK-IN may promote structural changes in regions associated with mood regulation and neuroplasticity, while also reducing neuronal damage in TRD patients.

重建萎缩的大脑:艾氯胺酮鼻腔治疗6个月扩大主要额叶和海马区域并降低重性抑郁症患者的神经丝血清水平。深度任务(抑郁症治疗)的概念验证。
目的:这项概念验证研究旨在评估鼻内艾氯胺酮(ESK-IN)对治疗难治性抑郁症(TDR)患者6个月以上脑容量和神经丝轻链(sNfL)的影响。方法:7例TRD患者在继续口服抗抑郁药的同时接受ESK-IN治疗。在基线、1、3和6个月时进行临床评估,并在基线和6个月时进行MRI扫描和采血。使用VolBrain2和DSI studio评估脑容量。结果:与对照组相比,TRD患者最初表现为脑岛(p = 0.0156)、额叶(p = 0.0228)、顶叶上(p = 0.0402)、颞叶上(p = 0.0216)、颞叶下(p = 0.0437)和皮层下如伏隔核(p = 0.0056)、壳核(p = 0.0083)、丘脑(p = 0.0102)、海马(p = 0.0001)等关键皮质区域体积(mm3)降低。在ESK-IN治疗6个月后,额叶皮质(p = 0.0295)、前扣带(p = 0.0496)和海马(p = 0.0015)以及与情绪调节相关的额旁海马(p = 0.0156和p = 0.0313)、额顶叶(p = 0.0496和p = 0.0156)和额斜束等体积和纤维束的脑容量均有所增加。同时,sNfL水平在治疗后下降,表明潜在的神经保护作用。结论:ESK-IN可能促进TRD患者情绪调节和神经可塑性相关区域的结构改变,同时减轻TRD患者的神经元损伤。
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来源期刊
CNS Spectrums
CNS Spectrums 医学-精神病学
CiteScore
6.20
自引率
6.10%
发文量
239
审稿时长
>12 weeks
期刊介绍: CNS Spectrums covers all aspects of the clinical neurosciences, neurotherapeutics, and neuropsychopharmacology, particularly those pertinent to the clinician and clinical investigator. The journal features focused, in-depth reviews, perspectives, and original research articles. New therapeutics of all types in psychiatry, mental health, and neurology are emphasized, especially first in man studies, proof of concept studies, and translational basic neuroscience studies. Subject coverage spans the full spectrum of neuropsychiatry, focusing on those crossing traditional boundaries between neurology and psychiatry.
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