Depression and anxiety in patients with endometriosis-associated chronic pain: Neuroimmune mechanisms mediated by inflammatory factors

doi:10.5498/wjp.v15.i10.107147

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World Journal of Psychiatry

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Retrospective Cohort Study

World J Psychiatry. Oct 19, 2025; 15(10): 107147
Published online Oct 19, 2025. doi: 10.5498/wjp.v15.i10.107147

Depression and anxiety in patients with endometriosis-associated chronic pain: Neuroimmune mechanisms mediated by inflammatory factors

Fan-Chun Yang, Yang Zhou, Shi-Yun Zhang, Rui Ma

Fan-Chun Yang, Department of Obstetrics and Gynecology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China

Yang Zhou, Shi-Yun Zhang, Department of Gynecologic Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China

Rui Ma, Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China

Co-first authors: Fan-Chun Yang and Yang Zhou.

Author contributions: Yang FC and Zhou Y contributed equally to this article, they are the co-first authors of this manuscript; Yang FC, Zhou Y, and Ma R contributed to the analysis of the manuscript, they were involved in the data analysis and writing of this article; Zhang SY and Yang FC are jointly responsible for data collection, design research, and have made equal contributions to this article; and all authors have read and approved the final manuscript.

Institutional review board statement: This study was approved by the Medical Ethics Committee of Shanghai Tenth People’s Hospital, approval No. SHSY-IEC-6.0/25K132/P01.

Informed consent statement: As this study was a retrospective one, informed consent forms were waived.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.

Data sharing statement: If you need data, please contact the corresponding author.

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: Rui Ma, MD, Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, No. 301 Yanchang Middle Road, Jing’an District, Shanghai 200072, China. ruima127@163.com

Received: May 23, 2025
Revised: June 24, 2025
Accepted: August 19, 2025
Published online: October 19, 2025
Processing time: 125 Days and 23.9 Hours

Abstract

BACKGROUND

Endometriosis affects approximately 10% of reproductive-age women and is frequently associated with chronic pelvic pain. Patients with endometriosis often experience comorbid depression and anxiety, but the underlying mechanisms connecting these conditions are unclear.

AIM

To assess the prevalence of depression and anxiety in endometriosis patients and explore neuroimmune mechanisms mediated via inflammatory biomarkers.

METHODS

A retrospective cohort study was conducted with 200 patients with endometriosis-associated chronic pain from June 2020 to December 2024. Depression and anxiety were assessed using validated psychological instruments. Inflammation biomarkers interleukin (ILs) (IL-6, IL-1β), tumor necrosis factor-alpha, C-reactive protein, and brain-derived neurotrophic factor were measured in serum. Pain severity was assessed using visual analog scales. Correlation and regression analyses were performed to examine relationships between inflammatory markers, pain severity, and psychological outcomes.

RESULTS

Among the 200 patients, 42.5% exhibited clinically significant depression and 51.0% showed anxiety symptoms. Serum levels of IL-6, IL-1β, tumor necrosis factor-alpha, and C-reactive protein were significantly higher in patients with comorbid depression and anxiety compared with those without psychological symptoms (P < 0.001). Brain-derived neurotrophic factor levels were lower in the depression group. Pain severity positively correlated with inflammatory marker levels and with depression and anxiety scores.

CONCLUSION

Overall, the findings suggest that inflammatory factors mediate a neuroimmune mechanism linking endometriosis-associated chronic pain with depression and anxiety. Therapeutic targets for managing psychological comorbidities in patients with endometriosis through anti-inflammatory interventions should be explored, and an integrated treatment approach addressing both physical and psychological symptoms is emphasized.

Keywords: Endometriosis; Chronic pain; Depression; Anxiety; Inflammation; Neuroimmune; Cytokines; Brain-derived neurotrophic factor

Core Tip: Endometriosis-associated chronic pain is frequently accompanied by depression and anxiety, but the underlying mechanisms remain unclear. This study highlights the role of inflammatory biomarkers, including interleukin-6, interleukin-1β, tumor necrosis factor-alpha, C-reactive protein, and brain-derived neurotrophic factor, in mediating these psychological comorbidities. Higher inflammatory marker levels correlate with increased pain severity and psychological distress. These findings suggest a neuroimmune link between endometriosis and mental health conditions, providing potential therapeutic targets. Addressing inflammation may improve both physical and psychological symptoms, emphasizing the need for an integrated treatment approach in managing endometriosis patients.