Sampada, Naseem M, Solanki M, Sharma R, Singh C, Sohal A. Pathophysiology of depression and anxiety in metabolic dysfunction-associated steatotic liver disease. World J Gastrointest Pathophysiol 2025; 16(4): 111029 [PMID: 41479860 DOI: 10.4291/wjgp.v16.i4.111029]
Corresponding Author of This Article
Aalam Sohal, MD, Department of Gastroenterology and Hepatology, Creighton University School of Medicine, 3216 NE 45th Pl Suite 212, Phoenix, AZ 85012, United States. aalamsohal@gmail.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Dec 22, 2025 (publication date) through Jan 12, 2026
Times Cited of This Article
Times Cited (0)
Journal Information of This Article
Publication Name
World Journal of Gastrointestinal Pathophysiology
ISSN
2150-5330
Publisher of This Article
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
Share the Article
Sampada, Naseem M, Solanki M, Sharma R, Singh C, Sohal A. Pathophysiology of depression and anxiety in metabolic dysfunction-associated steatotic liver disease. World J Gastrointest Pathophysiol 2025; 16(4): 111029 [PMID: 41479860 DOI: 10.4291/wjgp.v16.i4.111029]
World J Gastrointest Pathophysiol. Dec 22, 2025; 16(4): 111029 Published online Dec 22, 2025. doi: 10.4291/wjgp.v16.i4.111029
Pathophysiology of depression and anxiety in metabolic dysfunction-associated steatotic liver disease
Sampada, Mohammad Naseem, Mehul Solanki, Ragini Sharma, Carol Singh, Aalam Sohal
Sampada, Department of Internal Medicine, Punjab Institute of Medical Sciences, Jalandhar 144009, Punjab, India
Mohammad Naseem, Mehul Solanki, Department of Internal Medicine, Maulana Azad Medical College, New Delhi 110002, Delhi, India
Ragini Sharma, Department of Psychiatry, Maulana Azad Medical College, New Delhi 110002, Delhi, India
Carol Singh, Department of Internal Medicine, Dayanand Medical College and Hospital, Ludhiana 141001, Punjab, India
Aalam Sohal, Department of Gastroenterology and Hepatology, Creighton University School of Medicine, Phoenix, AZ 85012, United States
Author contributions: Sohal A conceptualized and designed the study; Sampada, Naseem M, Solanki M, Sharma R, and Singh C conducted the literature review, interpreted the data, created figures, and drafted the original manuscript; Sohal A supervised the study and made critical revisions.
Conflict-of-interest statement: The authors have no conflicts of interest, no grants or no financial support to acknowledge or disclose in the development of this article.
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: Aalam Sohal, MD, Department of Gastroenterology and Hepatology, Creighton University School of Medicine, 3216 NE 45th Pl Suite 212, Phoenix, AZ 85012, United States. aalamsohal@gmail.com
Received: June 23, 2025 Revised: July 31, 2025 Accepted: November 4, 2025 Published online: December 22, 2025 Processing time: 184 Days and 6.6 Hours
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease with a continually rising global prevalence and significant mortality rates. Emerging evidence suggests a strong association between MASLD and mental health disorders such as depression and anxiety. In addition to the shared risk factors such as obesity, type 2 diabetes and insulin resistance which contribute to this relationship through mechanisms involving systemic inflammation and oxidative stress; other pathophysiological mechanisms such as dysregulation of hypothalamic-pituitary-adrenal axis, neurotransmitter imbalances and gut dysbiosis have also been proposed to play a significant role. The current paper aims to review the pathophysiological mechanisms underlying the association between MASLD and mood disorders such as depression and anxiety. We note a bidirectional relationship between these two disorders, and the dual burden of both these disease processes can be alleviated by early detection and encouraging a more proactive and holistic approach through diet and lifestyle changes. This review summarizes the existing literature on association between MASLD and depression.
Core Tip: Metabolic dysfunction-associated steatotic liver disease is associated with mood disorders such as depression and anxiety through shared pathophysiological pathways. This review links systemic inflammation, hypothalamic-pituitary-adrenal axis dysregulation, gut dysbiosis, and neurotransmitter imbalances as mediators of this bidirectional relationship. We highlight how overlapping risk factors such as insulin resistance, obesity, sarcopenia, poor sleep, and physical inactivity exacerbate both the disease processes. Recognizing the mental health burden allows for improved patient outcomes and supports a holistic, lifestyle-focused treatment model that addresses both physical and mental health.
