Case Control Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Jun 19, 2025; 15(6): 105889
Published online Jun 19, 2025. doi: 10.5498/wjp.v15.i6.105889
Clinical manifestations of anxiety and depression in sepsis-associated encephalopathy and multi-omics identification of cluster of differentiation 38 as an early biomarker
Chun-Rong Wu, Hang-Li Zhu, Yu-Ting Sun, Shi-Hui Shen, Pei-Lin Shi, Yu-Hui Cui, Jian-Guo Tang, Chun-Hui Yang, Shang-Yuan Wang, Xiao-Li Ge, Shu-Ming Pan
Chun-Rong Wu, Shang-Yuan Wang, Shu-Ming Pan, Department of Emergency, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Chun-Rong Wu, Hang-Li Zhu, Yu-Hui Cui, Jian-Guo Tang, Chun-Hui Yang, Department of Trauma-Emergency and Critical Care Medicine Center, Shanghai Fifth People’s Hospital, Fudan University, Shanghai 200240, China
Yu-Ting Sun, Department of Emergency, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
Shi-Hui Shen, Pei-Lin Shi, Joint Center for Translational Medicine, Shanghai Fifth People’s Hospital, Fudan University and School of Life Science, East China Normal University, Shanghai 200011, China
Xiao-Li Ge, Department of Emergency, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
Co-first authors: Chun-Rong Wu and Hang-Li Zhu.
Co-corresponding authors: Xiao-Li Ge and Shu-Ming Pan.
Author contributions: Wu CR and Zhu HL designed the study; Sun YT, Shen SH, and Shi PL performed the experiments and collected data; Cui YH and Tang JG analyzed the data; Yang CH and Wang SY wrote the manuscript; Ge XL and Pan SM provided critical revisions to the manuscript; Wu CR, Zhu HL, Sun YT, Shen SH, Shi PL, Cui YH, Tang JG, Yang CH, Wang SY, Ge XL, and Pan SM reviewed and approved the final version.
Supported by the Shanghai Municipal Health Commission Medical New Technology Research and Translation Seed Program, No. 2024ZZ2052; Scientific Research Project funded by Shanghai Fifth People’s Hospital, Fudan University, No. 2023WYRH03 and No. 2025GZRFY05; Shanghai Putuo District Health System Clinical Medicine Discipline Construction Project, No. 2024tszk01; Shanghai Health System Key Discipline, No. 2024ZDXK0005; and Shanghai Minhang District Health and Family Planning Commission, No. 2024MWDXK01.
Institutional review board statement: This study was approved by the Ethics Committee of Shanghai Fifth People’s Hospital, Fudan University (Approval No. 2023-125).
Informed consent statement: Owing to the retrospective nature of the study, the ethics committee waived the need for obtaining informed consent. Patient data was anonymized and used in compliance with ethical standards to ensure privacy.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
STROBE statement: The authors have read the STROBE Statement—a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-a checklist of items.
Data sharing statement: The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. Owing to privacy and confidentiality concerns, the data will be shared only with researchers who meet the criteria for access to confidential data.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Shu-Ming Pan, PhD, Professor, Department of Emergency, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China. panshuming1103@163.com
Received: February 26, 2025
Revised: March 24, 2025
Accepted: April 27, 2025
Published online: June 19, 2025
Processing time: 92 Days and 2.1 Hours
Abstract
BACKGROUND

Sepsis-associated encephalopathy (SAE) is a common complication of sepsis, characterized by cognitive impairment, altered consciousness, and psychiatric symptoms, including anxiety and depression. These psychiatric symptoms often exacerbate the overall prognosis and quality of life of affected patients. However, the underlying metabolic and proteomic features associated with SAE-induced psychiatric symptoms remain poorly understood.

AIM

To investigate the clinical manifestations of anxiety and depression in patients with sepsis and SAE and to explore their associated metabolic and proteomic characteristics.

METHODS

A total of 88 patients were enrolled, comprising 30 healthy controls, 29 patients with sepsis, and 29 with SAE. Anxiety and depression symptoms were evaluated using the Hamilton anxiety rating scale (HAM-A) and Hamilton depression rating scale (HAM-D) in sepsis and SAE. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), and quality of life was measured using the 36-Item Short Form Health Survey. Plasma samples were analyzed for metabolomic and proteomic profiling. Metabolic alterations were identified through liquid chromatography-mass spectrometry, while protein expression was assessed using Olink targeted proteomics.

RESULTS

Compared to the sepsis group, patients with SAE exhibited significantly higher levels of anxiety (HAM-A: 15.2 ± 4.0 vs 10.4 ± 3.0, P = 0.012) and depression (HAM-D: 16.0 ± 3.5 vs 9.1 ± 2.3, P = 0.003). Cognitive function, as measured by MoCA, was notably impaired in the SAE group (MoCA: 18.5 ± 4.0 vs 24.5 ± 3.2, P = 0.007). Quality of life scores, particularly in physical functioning, emotional well-being, and mental health, were significantly lower in patients with SAE. Metabolomic and proteomic analyses revealed substantial alterations in oxidative stress and nicotinamide adenine dinucleotide (NAD+) metabolism pathways, with cluster of differentiation (CD) 38 emerging as a potential biomarker associated with psychiatric symptoms in SAE. Further validation in an independent cohort confirmed the diagnostic relevance of CD38.

CONCLUSION

This study highlights the significant psychological burden of SAE, manifested as anxiety and depression. Multi-omics analysis identified distinct metabolic alterations, particularly in NAD+ metabolism, that may contribute to psychiatric symptom development and progression. Furthermore, CD38 was identified as a promising biomarker for the early detection of SAE, providing potential avenues for early intervention and therapeutic targeting.

Keywords: Sepsis-associated encephalopathy; Anxiety; Depression; Cluster of differentiation 38; Metabolomics; Proteomics

Core Tip: Sepsis-associated encephalopathy (SAE) is linked to significant psychiatric symptoms, including anxiety and depression, which worsen patient outcomes. This study integrates multi-omics analysis to identify cluster of differentiation (CD) 38 as a key biomarker associated with nicotinamide adenine dinucleotide (NAD+) metabolism dysregulation in SAE. Elevated CD38 levels correlate with increased psychiatric burden and cognitive decline, suggesting its potential as an early diagnostic marker. A composite biomarker model incorporating CD38 improves the accuracy of predicting SAE. Targeting NAD+ metabolism may offer novel therapeutic strategies for mitigating neuropsychiatric symptoms in patients with SAE. These findings emphasize the need for early psychiatric screening and metabolic interventions in the management of SAE.