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ORIGINAL RESEARCH article

Front. Psychiatry

Sec. Neuroimaging

Volume 16 - 2025 | doi: 10.3389/fpsyt.2025.1675719

Resting-State fMRI Graph Theory Analysis for Predicting Selective Serotonin Reuptake Inhibitors Treatment Response in Adolescent Major Depressive Disorder

Provisionally accepted
Xue  MoXue Mo1Xuemei  LiXuemei Li2Mengqi  LiuMengqi Liu1Linlin  HuLinlin Hu1Qian  LiQian Li1Jie  WangJie Wang1Haiqin  DengHaiqin Deng1Fajin  LvFajin Lv1Xinyu  ZhouXinyu Zhou2Yun  MaoYun Mao1*Yang  HuangYang Huang1*
  • 1Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
  • 2Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

The final, formatted version of the article will be published soon.

Background: Substantial interindividual variability exists in the response of adolescents with major depressive disorder (MDD) to selective serotonin reuptake inhibitors (SSRIs), and reliable early predictors of treatment response are lacking. Methods: Resting-state functional magnetic resonance imaging (fMRI) data and clinical scale scores were collected from 69 adolescents with first-episode, drug-naïve MDD. Based on treatment response assessed after 8 weeks of SSRIs therapy, participants were categorized into a responder group (n=37) and a non-responder group (n=32). Graph-theoretical analysis was then performed on the pre-treatment resting-state functional networks of both groups. Results: Significant group differences emerged in several global attribute metrics and multiple brain region node attribute metrics (including the left middle frontal gyrus, hippocampus, parahippocampal gyrus, amygdala, pallidum, as well as the right anterior cingulate cortex and inferior parietal lobule). Partial correlation analyses revealed negative correlations between nodal efficiency in the left middle frontal gyrus, hippocampus, and parahippocampal gyrus, as well as degree centrality in the right anterior cingulate gyrus, and the reduction rate in Hamilton Depression Rating Scale-17 score. Furthermore, logistic regression analysis identified lower nodal efficiency in the right inferior parietal lobule and higher clustering coefficient in the left pallidum as significant predictors of SSRIs treatment response. Conclusions: Pre-treatment functional network topological metrics differentiating responders and non-responders demonstrate potential as predictors for SSRIs treatment response in adolescents with MDD.

Keywords: Major Depressive Disorder, adolescents, Selective Serotonin Reuptake Inhibitors, functional brain networks, graph theory

Received: 29 Jul 2025; Accepted: 18 Sep 2025.

Copyright: © 2025 Mo, Li, Liu, Hu, Li, Wang, Deng, Lv, Zhou, Mao and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Yun Mao, maoyun1979@163.com
Yang Huang, huangyang@hospital.cqmu.edu.cn

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