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The impact of childhood trauma on brain structural connectivity in adolescent major depressive disorder: A graph-based analysis.

April 27, 2026pubmed logopapers

Authors

Zhang J,Li X,Liu M,Huang Y,Wang W,Zhu T,Yan T,Yang Y,Hu L,Wang J,Li Q,Qin K,Li C,McNamara RK,DelBello MP,Lei D,Zhou X

Affiliations (8)

  • College of Artificial Intelligence Medicine, Chongqing Medical University, Chongqing, 400016, China.
  • Department of Psychiatry, Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
  • Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
  • Mental Health Center, Taihe Hospital, Hubei University of Medicine, Shiyan, China; Department of Radiology, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
  • Department of Clinical Neurosciences, University of Cambridge, CB2 1TN, United Kingdom.
  • Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, 45219, OH, USA.
  • College of Artificial Intelligence Medicine, Chongqing Medical University, Chongqing, 400016, China; Department of Psychiatry, Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. Electronic address: [email protected].
  • Department of Psychiatry, Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. Electronic address: [email protected].

Abstract

Childhood trauma (CT) significantly increases vulnerability to adolescent major depressive disorder (MDD), yet the underlying neurobiological mechanisms remain unclear. This study applied graph-theoretical analysis to structural MRI data to examine how CT influences brain structural networks and antidepressant treatment outcomes in adolescent MDD. A total of 339 adolescents with MDD and 152 healthy controls (HC) were recruited. The MDD group was subdivided into those with (MDD-CT; n = 209) and without (MDD-nCT; n = 106) a history of CT. Compared with HC, both MDD subgroups exhibited a shift toward more randomized network properties. Notably, MDD-CT was characterized by more severe depressive and anxiety symptoms and showed focal disruptions within the default mode network (DMN), whereas MDD-nCT involved broader alterations across the central executive, salience, and DMN networks. Following antidepressant treatment, MDD-CT had a lower response rate than MDD-nCT (48.24% vs. 65.38%). Significant group-by-time interactions were observed in the right amygdala and caudate nucleus. Moreover, a machine learning model combining autoencoder-based feature extraction with support vector machine classification predicted treatment response with 89.8% accuracy. This study revealed unique and common structural network abnormalities in MDD-CT and MDD-nCT, suggesting that childhood trauma leads to focused disruptions in the DMN. Treatment-induced changes in the amygdala and caudate nucleus may contribute to poorer outcomes in MDD-CT. These findings provide insights into the neurobiological underpinnings of trauma-related depression and highlight the potential of structural connectivity markers for guiding biomarker-informed treatment strategies in adolescent MDD.

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Journal Article

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