High Baseline Plasma Anthranilic Acid Predicts Remission Upon Acute-Series Ketamine Infusion for Treatment-Resistant Depression

IF 4 Q2 NEUROSCIENCES

Biological psychiatry global open science Pub Date : 2025-04-12 DOI:10.1016/j.bpsgos.2025.100503

Stephen A. Murata , Zachary B. Madaj , Colt D. Capan , Ryan D. Sheldon , Rif S. El-Mallakh , Sagar V. Parikh , William V. Bobo , Fernando S. Goes , Owen M. Wolkowitz , Jennifer L. Vande Voort , Louis J. Nykamp , Balwinder Singh , Gustavo C. Medeiros , Erik B. Nelson , Michael E. Thase , Gregory F. Oxenkrug , Mark A. Frye , John F. Greden , Eric D. Achtyes , Lena C. Brundin

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Abstract

Background

Treatment-resistant depression (TRD) remains a challenge, but intravenous racemic ketamine offers rapid antidepressant effects. Reliable biomarkers are needed. In this study, we examined kynurenine pathway metabolites and inflammatory cytokines as predictors of ketamine response.

Methods

The Bio-K study was a multicenter, open-label trial of 74 patients with TRD who received 3 ketamine infusions over 11 days. Remission (Montgomery–Åsberg Depression Rating Scale [MADRS] score ≤9) was assessed 24 hours post infusion 3, with a subset of study participants continuing weekly infusions. Plasma biomarkers (9 kynurenines, 14 cytokines) were measured at baseline and post infusion. Mixed-effects models and logistic regression analyses were used, adjusting for sex, age, body mass index, benzodiazepine use, and baseline MADRS scores. Second-generation p values were used to determine significance.

Results

Of the 74 participants, 52% (n = 38) achieved remission. Higher baseline anthranilic acid (AA) levels predicted remission (β = −0.93, p = .02). Composite ratios, including AA:intercellular adhesion molecule-1 (ICAM-1) (β = −1.15, p = .002) and AA:tryptophan (TRP) (β = −0.98, p = .007), significantly improved predictive accuracy (area under the receiver operating characteristic curve = 0.75 vs. 0.64, p = .03). The findings were independent of demographic and clinical covariates.

Conclusions

Elevated AA levels and AA-based biomarker ratios predicted ketamine remission in patients with TRD, supporting biomarker-driven personalized treatment. These findings highlight immunometabolic mechanisms in ketamine response.

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高基线血浆邻氨基苯酸预测急性系列氯胺酮输注治疗难治性抑郁症的缓解

背景：难治性抑郁症（TRD）仍然是一个挑战，但静脉外消旋氯胺酮提供了快速的抗抑郁作用。需要可靠的生物标志物。在这项研究中，我们检测了犬尿氨酸途径代谢物和炎症细胞因子作为氯胺酮反应的预测因子。方法Bio-K研究是一项多中心、开放标签的试验，74例TRD患者在11天内接受3次氯胺酮输注。在注射3后24小时评估缓解（Montgomery -Åsberg抑郁评定量表[MADRS]评分≤9），其中一部分研究参与者每周继续注射。血浆生物标志物（9种犬尿氨酸，14种细胞因子）在基线和输注后测量。采用混合效应模型和logistic回归分析，调整性别、年龄、体重指数、苯二氮卓类药物使用和MADRS基线评分。采用第二代p值确定显著性。结果74名参与者中，52% （n = 38）获得缓解。较高的基线邻氨基苯酸（AA）水平预示缓解（β = - 0.93, p = 0.02）。包括AA：细胞间粘附分子-1 (ICAM-1) （β = - 1.15, p = .002）和AA：色氨酸（TRP）（β = - 0.98, p = .007）在内的复合比率显著提高了预测准确性（受试者工作特征曲线下面积= 0.75 vs. 0.64, p = .03）。研究结果独立于人口统计学和临床协变量。结论AA水平升高和基于AA的生物标志物比值预测TRD患者氯胺酮缓解，支持生物标志物驱动的个性化治疗。这些发现强调了氯胺酮反应的免疫代谢机制。

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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