Lack of relationships between ketamine treatment and peripheral neurotrophic and inflammatory factors in a randomized controlled ketamine trial of major depressive disorder

IF 8.8 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity Pub Date : 2025-04-04 DOI:10.1016/j.bbi.2025.04.006

Manivel Rengasamy , Benjamin Panny , Zakary Hutchinson , Anna Marsland , Tessa Kovats , Angela Griffo , Crystal Spotts , Robert H. Howland , Meredith L. Wallace , Sanjay J. Mathew , Shabnam Hossein , Rebecca B. Price

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引用次数: 0

Abstract

Background

Ketamine is a rapid-acting treatment for treatment-resistant depression (TRD), though mechanisms related to ketamine’s effects remain unclear. Blood-based neurotrophic and inflammatory factors (NIFs; e.g., brain-derived neurotrophic factor, interleukin-6) have emerged as markers potentially linked to ketamine and ketamine treatment response.

Methods

In this secondary analysis of a randomized controlled trial (RCT), 133 adults with TRD received a single-dose infusion of ketamine (n = 89; 0.5 mg/kg) or saline (n = 44) and provided measures of peripheral blood NIF levels and depression severity across a five-day post-infusion period. Differences between ketamine and saline groups were examined for (1) NIF levels, (2) associations between NIF trajectories and depression score trajectories, and (3) associations between baseline NIF levels and depression score trajectories. Subgroup sensitivity analyses examined identical relationships within many (n = 28) discrete subgroups of individuals.

Results

No differences were found between ketamine and saline cohorts for NIF trajectories, associations of NIF and depression trajectories, or associations of baseline NIF levels and depression trajectories. On subgroup analyses, in participants with lower BMI (BMI < 25; n = 66), increasing interleukin-1 receptor antagonist (IL-1RA) trajectories post-ketamine were associated with less improvement in depression in the first day post-infusion.

Discussion

Associations between ketamine treatment and peripheral neurotrophic/inflammatory factors were not detected in our RCT of 133 adults with TRD. The sole exception across exhaustive sensitivity analyses was that, in individuals with low BMI, increases in IL-1RA levels may be linked to worse immediate treatment response. Future research investigating CNS-specific NIF activity is needed to more definitively test the posited role of NIFs in ketamine’s antidepressant mechanisms.

查看原文本刊更多论文

背景：氯胺酮是治疗难治性抑郁症（TRD）的一种速效疗法，但氯胺酮的作用机制仍不清楚。血液中的神经营养因子和炎症因子（NIFs；如脑源性神经营养因子、白细胞介素-6）已成为可能与氯胺酮和氯胺酮治疗反应相关的标志物：在这项随机对照试验（RCT）的二次分析中，133名患有TRD的成人接受了氯胺酮（89人，0.5毫克/千克）或生理盐水（44人）的单剂量输注，并在输注后的五天内提供了外周血NIF水平和抑郁严重程度的测量指标。氯胺酮组和生理盐水组之间的差异主要表现在：（1）NIF水平；（2）NIF轨迹与抑郁评分轨迹之间的关联；（3）基线NIF水平与抑郁评分轨迹之间的关联。亚组敏感性分析研究了许多（n = 28）离散亚组中的相同关系：结果：氯胺酮队列和生理盐水队列之间的 NIF 轨迹、NIF 与抑郁轨迹的关联或基线 NIF 水平与抑郁轨迹的关联均未发现差异。在亚组分析中，在体重指数较低的参与者中（体重指数小于25；n = 66），氯胺酮后白细胞介素-1受体拮抗剂（IL-1RA）轨迹的增加与输注后第一天抑郁改善程度较低有关：讨论：在我们对133名患有TRD的成人进行的研究中，未发现氯胺酮治疗与外周神经营养/炎症因子之间存在关联。在详尽的敏感性分析中，唯一的例外是，在体重指数较低的患者中，IL-1RA水平的升高可能与较差的即时治疗反应有关。未来需要对中枢神经系统特异性NIF活性进行调查研究，以便更明确地检验NIF在氯胺酮抗抑郁机制中的假设作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Brain, Behavior, and Immunity 医学-免疫学

CiteScore

29.60

自引率

2.00%

发文量

290

审稿时长

28 days

期刊介绍： Established in 1987, Brain, Behavior, and Immunity proudly serves as the official journal of the Psychoneuroimmunology Research Society (PNIRS). This pioneering journal is dedicated to publishing peer-reviewed basic, experimental, and clinical studies that explore the intricate interactions among behavioral, neural, endocrine, and immune systems in both humans and animals. As an international and interdisciplinary platform, Brain, Behavior, and Immunity focuses on original research spanning neuroscience, immunology, integrative physiology, behavioral biology, psychiatry, psychology, and clinical medicine. The journal is inclusive of research conducted at various levels, including molecular, cellular, social, and whole organism perspectives. With a commitment to efficiency, the journal facilitates online submission and review, ensuring timely publication of experimental results. Manuscripts typically undergo peer review and are returned to authors within 30 days of submission. It's worth noting that Brain, Behavior, and Immunity, published eight times a year, does not impose submission fees or page charges, fostering an open and accessible platform for scientific discourse.