Nan Zhou, Xiaolei Shi, Runhua Wang, Chengyu Wang, Xiaofeng Lan, Guanxi Liu, Weicheng Li, Yanling Zhou, Yuping Ning
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引用次数: 0
Abstract
Background: Major depressive disorder (MDD) is characterized by persistent feelings of sadness and loss of interest. Ketamine has been widely used to treat MDD owing to its rapid effect in relieving depressive symptoms. Importantly, not all patients respond to ketamine treatment. Identifying sub-populations who will benefit from ketamine, as well as those who may not, prior to treatment initiation, would significantly advance precision medicine in patients with MDD.
Methods: Here, we used mass spectrometry-based plasma proteomics to analyze matched pre- and post-ketamine treatment samples from a cohort of 30 MDD patients whose treatment outcomes and demographic and clinical characteristics were considered.
Results: Ketamine responders and non-responders were identified according to their individual outcomes after two weeks of treatment. We analyzed proteomic alterations in post-treatment samples from responders and non-responders and identified a collection of six proteins pivotal to the antidepressive effect of ketamine. Subsequent co-regulation analysis revealed that pathways related to immune response were involved in ketamine response. By comparing the proteomic profiles of samples from the same individuals at the pre- and post-treatment time points, dynamic proteomic rearrangements induced by ketamine revealed that immune-related processes were activated in association with its antidepressive effect. Furthermore, receiver operating characteristic curve analysis of pre-treatment samples revealed three proteins with strong predictive performance in determining the response of patients to ketamine before receiving treatment.
Conclusions: These findings provide valuable knowledge about ketamine response, which will ultimately lead to more personalized and effective treatments for patients.
Trial registration: The study was registered in the Chinese Clinical Trials Registry (ChiCTR-OOC-17012239) on May 26, 2017.
期刊介绍：
Cell Biology and Toxicology (CBT) is an international journal focused on clinical and translational research with an emphasis on molecular and cell biology, genetic and epigenetic heterogeneity, drug discovery and development, and molecular pharmacology and toxicology. CBT has a disease-specific scope prioritizing publications on gene and protein-based regulation, intracellular signaling pathway dysfunction, cell type-specific function, and systems in biomedicine in drug discovery and development. CBT publishes original articles with outstanding, innovative and significant findings, important reviews on recent research advances and issues of high current interest, opinion articles of leading edge science, and rapid communication or reports, on molecular mechanisms and therapies in diseases.
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