AUTHOR=Mo Xue , Li Xuemei , Liu Mengqi , Hu Linlin , Li Qian , Wang Jie , Deng Haiqing , Lv Fajin , Zhou Xinyu , Mao Yun , Huang Yang TITLE=Resting-state fMRI graph theory analysis for predicting selective serotonin reuptake inhibitors treatment response in adolescent major depressive disorder JOURNAL=Frontiers in Psychiatry VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2025.1675719 DOI=10.3389/fpsyt.2025.1675719 ISSN=1664-0640 ABSTRACT=BackgroundSubstantial 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.MethodsResting-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.ResultsSignificant 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.ConclusionsPre-treatment functional network topological metrics differentiating responders and non-responders demonstrate potential as predictors for SSRIs treatment response in adolescents with MDD.