Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Nov 19, 2024; 14(11): 1746-1754
Published online Nov 19, 2024. doi: 10.5498/wjp.v14.i11.1746
Major depressive disorder is associated with mitochondrial ND6 T14502C mutation in two Han Chinese families
Pan Jing, Hai-Hang Yu, Ting-Ting Wu, Bi-Hua Yu, Ming Liang, Ting-Ting Xia, Xue-Wen Xu, Ting Xu, Ling-Jiang Liu, Xiao-Bin Zhang
Pan Jing, Suzhou Medical College, Soochow University, Suzhou 215123, Jiangsu Province, China
Pan Jing, Hai-Hang Yu, Ting-Ting Wu, Bi-Hua Yu, Xue-Wen Xu, Ting Xu, Ling-Jiang Liu, Department of Psychiatry, Affiliated Kangning Hospital of Ningbo University, Ningbo Kangning Hospital, Ningbo 315201, Zhejiang Province, China
Ming Liang, Ting-Ting Xia, Department of Psychiatry, Xiangshan Third People’s Hospital, Ningbo 315700, Zhejiang Province, China
Xiao-Bin Zhang, Department of Psychiatry, Suzhou Guangji Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou 215137, Jiangsu Province, China
Author contributions: Jing P contributed to conceptualization, methodology, data curation, writing of the original draft, visualization, and formal analysis; Yu HH, Wu TT, Yu BH, Liang M, Xia TT, Xu XW, Xu T, Liu LJ contributed to data collection, writing of the original draft, review and editing; Zhang XB contributed to conception and design, assistance in drafting the article and revising it critically for important intellectual content; All authors contributed to the article, agreed to submit it to the current journal, and approved the submitted version.
Supported by the Zhejiang Medical and Health Science and Technology Project, No. 2023KY1126; Suzhou Key Technologies Program, No. SKY2021063; Jiangsu Province Social Development Project, No. BE2020764; Suzhou Clinical Medical Center for Mood Disorders, No. Szlcyxzx202109; Suzhou Clinical Key Disciplines for Geriatric Psychiatry, No. SZXK202116; and Suzhou Key Laboratory, No. SZS2024016.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Ningbo Kangning Hospital Institutional Review Board, Approval No. NBKNYY-2022-LC-29.
Institutional animal care and use committee statement: No animal experiments were involved in this study.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: The data are available from the corresponding author on reasonable request.
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: Xiao-Bin Zhang, PhD, Professor, Department of Psychiatry, Suzhou Guangji Hospital, The Affiliated Guangji Hospital of Soochow University, No. 11 Guangqian Road, Suzhou 215137, Jiangsu Province, China. zhangxiaobim@163.com
Received: February 28, 2024
Revised: September 6, 2024
Accepted: October 28, 2024
Published online: November 19, 2024
Processing time: 253 Days and 0.3 Hours
Abstract
BACKGROUND

Globally, the World Health Organization ranks major depressive disorder (MDD) as the leading cause of disability. However, MDD molecular etiology is still poorly understood.

AIM

To explore the possible association between mitochondrial ND6 T14502C mutation and MDD.

METHODS

Clinical data were collected from two pedigrees, and detailed mitochondrial genomes were obtained for the two proband members. The assessment of the resulting variants included an evaluation of their evolutionary conservation, allelic frequencies, as well as their structural and functional consequences. Detailed mitochondrial whole genome analysis, phylogenetic, and haplotype analysis were performed on the probands.

RESULTS

Herein, we reported the clinical, genetic, and molecular profiling of two Chinese families afflicted with MDD. These Chinese families exhibited not only a range of onset and severity ages in their depression but also extremely low penetrances to MDD. Sequence analyses of mitochondrial genomes from these pedigrees have resulted in the identification of a homoplasmic T14502C (I58V) mutation. The polymorphism is located at a highly conserved isoleucine at position 58 of ND6 and distinct mitochondrial DNA (mtDNA) polymorphisms originating from haplogroups M10 and H2.

CONCLUSION

Identifying the T14502C mutation in two individuals with no genetic relation who exhibit symptoms of depression provides compelling evidence that this mutation may be implicated in MDD development. Nonetheless, the two Chinese pedigrees that carried the T14502C mutation did not exhibit any functionally significant mutations in their mtDNA. Therefore, the phenotypic expression of the T14502C mutation related to MDD may be influenced by the nuclear modifier gene(s) or environmental factors.

Keywords: Major depressive disorder; Mitochondrial DNA; ND6 T14502C; Mutation; Haplogroup; Chinese

Core Tip: In this study, we report the clinical, genetic and molecular characterization of two Chinese families with major depressive disorder (MDD). Sequence analyses of mitochondrial genomes from these pedigrees revealed homoplasmic T14502C (I58V) mutation. This observation of the T14502C mutation in two genetically unrelated individuals who suffer from depression strongly suggests that this mutation might play a role in the development of MDD.