Retrospective Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Feb 19, 2024; 14(2): 276-286
Published online Feb 19, 2024. doi: 10.5498/wjp.v14.i2.276
Neuropathological characteristics of abnormal white matter functional signaling in adolescents with major depression
Xin-Lin Huang, Ju Gao, Yong-Ming Wang, Feng Zhu, Jing Qin, Qian-Nan Yao, Xiao-Bin Zhang, Hong-Yan Sun
Xin-Lin Huang, Qian-Nan Yao, Imaging and Nuclear Medicine, Jiamusi University, Jiamusi 154000, Heilongjiang Province, China
Ju Gao, Feng Zhu, Xiao-Bin Zhang, Department of Psychiatry, The Affiliated Guangji Hospital of Soochow University, Suzhou 215137, Jiangsu Province, China
Yong-Ming Wang, School of Biology & Basic Medical Sciences, Medical College of Soochow University, Suzhou 215137, Jiangsu Province, China
Jing Qin, Department of Radiology, Shanghai Anting Hospital, Shanghai 20000, China
Hong-Yan Sun, Department of Radiology, The Affiliated Guangji Hospital of Soochow University, Suzhou 215137, Jiangsu Province, China
Co-first authors: Xin-Lin Huang and Ju Gao.
Co-corresponding authors: Xiao-Bin Zhang and Hong-Yan Sun.
Author contributions: Huang XL, Sun HY, Gao J and Zhang XB conceived the study and drafted the manuscript; Huang XL and Yao QN completed all data collection; Huang XL and Wang YM participated in data analysis and acquired imaging data; Qin J and Zhu F conducted the literature search; All authors contributed to writing and revision of the manuscript, and approved the final version to be published. Huang XL and Gao J, they share co-first authorship, and they have made equal contributions to this paper. They undertook responsibilities for explored research ideas, data collection, data curation, and the writing of the original draft. Sun HY and Zhang XB, they share co-corresponding authorship, and they have made equal contributions to this paper. They were involved in conceptualization, securing funding, supervision, editing and modifying.
Supported by the Suzhou Clinical Medical Center for Mood Disorders, No. Szlcyxzx202109; and Jiangsu Provincial Department of Science and Technology for Social Development-General Project, No. BE2022735.
Institutional review board statement: The study was approved by the Ethics Committee of Suzhou Guangji Hospital.
Informed consent statement: All patients gave informed consent.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
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:
Corresponding author: Hong-Yan Sun, MD, PhD, Chief Doctor, Department of Radiology, The Affiliated Guangji Hospital of Soochow University, No. 11 Guangqian Road, Suzhou 215137, Jiangsu Province, China.
Received: November 23, 2023
Peer-review started: November 23, 2023
First decision: December 6, 2023
Revised: December 13, 2023
Accepted: January 8, 2024
Article in press: January 8, 2024
Published online: February 19, 2024

Major depression disorder (MDD) constitutes a significant mental health concern. Epidemiological surveys indicate that the lifetime prevalence of depression in adolescents is much higher than that in adults, with a corresponding increased risk of suicide. In studying brain dysfunction associated with MDD in adole-scents, research on brain white matter (WM) is sparse. Some researchers even mistakenly regard the signals generated by the WM as noise points. In fact, studies have shown that WM exhibits similar blood oxygen level-dependent signal fluctuations. The alterations in WM signals and their relationship with disease severity in adolescents with MDD remain unclear.


To explore potential abnormalities in WM functional signals in adolescents with MDD.


This study involved 48 adolescent patients with MDD and 31 healthy controls (HC). All participants were assessed using the Patient Health Questionnaire-9 Scale and the mini international neuropsychiatric interview (MINI) suicide inventory. In addition, a Siemens Skyra 3.0T magnetic resonance scanner was used to obtain the subjects' image data. The DPABI software was utilized to calculate the WM signal of the fractional amplitude of low frequency fluctuations (fALFF) and regional homogeneity, followed by a two-sample t-test between the MDD and HC groups. Independent component analysis (ICA) was also used to evaluate the WM functional signal. Pearson’s correlation was performed to assess the relationship between statistical test results and clinical scales.


Compared to HC, individuals with MDD demonstrated a decrease in the fALFF of WM in the corpus callosum body, left posterior limb of the internal capsule, right superior corona radiata, and bilateral posterior corona radiata [P < 0.001, family-wise error (FWE) voxel correction]. The regional homogeneity of WM increased in the right posterior limb of internal capsule and left superior corona radiata, and decreased in the left superior longitudinal fasciculus (P < 0.001, FWE voxel correction). The ICA results of WM overlapped with those of regional homo-geneity. The fALFF of WM signal in the left posterior limb of the internal capsule was negatively correlated with the MINI suicide scale (P = 0.026, r = -0.32), and the right posterior corona radiata was also negatively correlated with the MINI suicide scale (P = 0.047, r = -0.288).


Adolescents with MDD involves changes in WM functional signals, and these differences in brain regions may increase the risk of suicide.

Keywords: White matter, Regional homogeneity, The fractional amplitude of low-frequency fluctuations, Independent component analysis, Adolescents, Major depression disorders

Core Tip: This groundbreaking study investigates white matter (WM) functional signals in adolescents with major depressive disorder (MDD), an area often overlooked in research. Utilizing advanced imaging techniques, the study identifies specific abnormalities in WM signals, revealing decreased fractional amplitude of low frequency fluctuations in key regions and altered regional homogeneity and independent component analysis patterns. Notably, these changes correlate with suicidality scales, indicating a potential link between WM anomalies and severity of depression. The study pioneers a crucial shift in understanding MDD's neuropathogenesis, offering novel insights and support for future research and predictive measures.