Contrastive functional connectivity defines neurophysiology-informed symptom dimensions in major depression.

Journal: Cell reports. Medicine
Published Date: May 28, 2025

Abstract

Major depressive disorder (MDD) is highly heterogeneous, posing challenges for effective treatment due to complex interactions between clinical symptoms and neurobiological features. To address this, we apply contrastive principal-component analysis to fMRI-based resting-state functional connectivity, isolating disorder-specific variations by contrasting data from 233 MDD patients and 285 healthy controls. Subsequently, we use sparse canonical correlation analysis to identify two significant dimensions linking distinct brain circuits with clinical profiles. One dimension relates to an internalizing-externalizing symptom spectrum involving visual and limbic networks and is associated with cognitive task reaction times. The other dimension, linked to personality traits protective against depression (e.g., extraversion), is driven by dorsal attention network connections and correlates with cognitive control and psychomotor performance. This approach illuminates stable symptom dimensions and their neurophysiological underpinnings, aiding in precision phenotyping for MDD and supporting the development of targeted, individualized therapeutic strategies for mental health care.

Authors

  • Hao Zhu
    State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology Wuhan 430070 PR China chang@whut.edu.cn suntl@whut.edu.cn.
  • Xiaoyu Tong
    Department of Radiology, First Affiliated Hospital of Dalian Medical University, Shahekou District, Lianhe Road, Dalian, Liaoning, China (S.W., X.T., Y.F., M.H., Y.L., X.F.).
  • Nancy B Carlisle
    Department of Psychology, Lehigh University, Bethlehem, PA 18015, USA. Electronic address: nbc415@lehigh.edu.
  • Hua Xie
    Department of Gynecology, Jilin Central General Hospital, Jilin, China.
  • Corey J Keller
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA. ckeller1@stanford.edu.
  • Desmond J Oathes
    Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, PA, USA.
  • Feng Liu
    Department of Vascular and Endovascular Surgery, The First Medical Center of Chinese PLA General Hospital, 100853 Beijing, China.
  • Charles B Nemeroff
    Center for Psychedelic Research and Therapy, Department of Psychiatry and Behavioral Sciences, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
  • Gregory A Fonzo
    Center for Psychedelic Research and Therapy, Department of Psychiatry and Behavioral Sciences, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA. Electronic address: gfonzo@austin.utexas.edu.
  • Yu Zhang
    College of Marine Electrical Engineering, Dalian Maritime University, Dalian, China.

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