Zou YZ, Chen T, Wang CB. Differential diagnosis of bipolar II disorder and major depressive disorder: Integrating multimodal approaches to overcome clinical challenges. World J Psychiatry 2026; 16(1): 111800 [DOI: 10.5498/wjp.v16.i1.111800]
Corresponding Author of This Article
Chao-Ban Wang, Department of Pediatrics Hematology, West China Second University Hospital, Sichuan University, No. 1416 Chenglong Avenue, Jinjiang District, Chengdu 610000, Sichuan Province, China. chaobanwang@scu.edu.cn
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Psychology, Clinical
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Minireviews
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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/
Jan 19, 2026 (publication date) through Dec 31, 2025
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Publication Name
World Journal of Psychiatry
ISSN
2220-3206
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Zou YZ, Chen T, Wang CB. Differential diagnosis of bipolar II disorder and major depressive disorder: Integrating multimodal approaches to overcome clinical challenges. World J Psychiatry 2026; 16(1): 111800 [DOI: 10.5498/wjp.v16.i1.111800]
World J Psychiatry. Jan 19, 2026; 16(1): 111800 Published online Jan 19, 2026. doi: 10.5498/wjp.v16.i1.111800
Differential diagnosis of bipolar II disorder and major depressive disorder: Integrating multimodal approaches to overcome clinical challenges
Yuan-Zi Zou, Ting Chen, Chao-Ban Wang
Yuan-Zi Zou, Department of Pediatrics Intensive Care Unit Nursing, West China Second University Hospital, Sichuan University, Chengdu 610000, Sichuan Province, China
Ting Chen, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610000, Sichuan Province, China
Chao-Ban Wang, Department of Pediatrics Hematology, West China Second University Hospital, Sichuan University, Chengdu 610000, Sichuan Province, China
Co-corresponding authors: Ting Chen and Chao-Ban Wang.
Author contributions: Zou YZ drafted the paper; Chen T drafted and rewritten the paper; Wang CB conception and design, administrative support. Regarding the designation of two co-corresponding authors, we confirm that both Wang CB and Chen T have made substantial and equal contributions to the conceptualization, design, and execution of this review. Throughout the preparation of the manuscript, both authors actively participated in drafting, critically revising all sections, and ensuring the scientific accuracy, coherence, and intellectual rigor of the work. They jointly supervised the project, provided essential guidance, and approved the final version submitted for publication. Given their shared leadership and significant involvement at every stage of the manuscript’s development, it is appropriate to list both as co-corresponding authors. Both take full responsibility for the integrity of the work and are equally available to handle correspondence concerning the published article. This arrangement reflects their equitable contributions and aligns.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
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: Chao-Ban Wang, Department of Pediatrics Hematology, West China Second University Hospital, Sichuan University, No. 1416 Chenglong Avenue, Jinjiang District, Chengdu 610000, Sichuan Province, China. chaobanwang@scu.edu.cn
Received: July 10, 2025 Revised: August 12, 2025 Accepted: October 29, 2025 Published online: January 19, 2026 Processing time: 174 Days and 19.9 Hours
Abstract
Clinically differentiating bipolar II disorder (BD-II) from major depressive disorder (MDD) remains a significant challenge in modern psychiatry. These two conditions share substantial clinical symptomatology, making accurate diagnosis difficult in routine clinical practice. Misdiagnosis may lead to inappropriate treatment strategies, increased psychological and physical burdens, reduced quality of life, and impaired social functioning. Genetic overlap may partially explain the clinical similarities between MDD and BD-II, and biomarkers along with neuroimaging techniques are receiving increasing attention as tools to aid in diagnosis. For example, electroencephalography has been shown to effectively distinguish between unipolar depression and bipolar depression; serum levels of glycogen synthase kinase-3 have also been investigated as a potential tool for differentiating between the two disorders. A comprehensive assessment integrating clinical characteristics, genetic basis research, and multimodal evaluations using neuroimaging and biomarkers through a multidisciplinary approach will help enhance clinicians' ability to distinguish between MDD and BD-II. By improving diagnostic accuracy, more personalized and effective treatment strategies can be developed, ultimately improving patients' health outcomes and quality of life.
Core Tip: A multidisciplinary approach that combines detailed clinical evaluation, insights into genetic underpinnings, and multimodal assessments using neuroimaging and biomarkers may substantially improve clinicians’ ability to distinguish between major depressive disorder (MDD) and bipolar II disorder (BD-II). Enhanced diagnostic accuracy can lead to more tailored and effective treatment strategies, ultimately improving patients' health outcomes and quality of life. This mini-review aims to summarize current evidence on the distinguishing features of MDD and BD-II-focusing on clinical symptoms, genetic profiles, neuroimaging findings, and biomarker signatures-and discusses the potential of machine learning approaches to further refine and support the differential diagnostic process.
