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Multilevel brain functional connectivity and task-based representations explaining heterogeneity in major depressive

Qi Liu1, Xinqi Zhou2, Chunmei Lan3

  • 1The Center of Psychosomatic Medicine, Sichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.

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Major depressive disorder (MDD) shows diverse brain activity patterns. This study identified two distinct MDD subtypes with opposing functional connectivity, suggesting personalized treatments are crucial for effective intervention.

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Medical Imaging

Background:

  • Major depressive disorder (MDD) presents significant clinical and biological heterogeneity.
  • Understanding the underlying neurophysiological mechanisms of MDD is critical for targeted interventions.

Purpose of the Study:

  • To identify distinct subgroups within Major Depressive Disorder (MDD) based on multilevel functional brain connectivity.
  • To validate these subtypes and explore their neural representations during specific cognitive tasks.

Main Methods:

  • Utilized static and dynamic functional connectivity from resting-state fMRI in a large cohort (N=2428) to map developmental trajectories.
  • Employed a normative model to identify MDD subgroups.
  • Validated subtypes using an independent cohort (N=72) with resting-state and task-based fMRI.

Main Results:

  • Identified two reproducible MDD subtypes with comparable clinical severity but opposing patterns of brain functional deviations.
  • MDD subtype 1 showed positive deviations in frontoparietal/default mode networks and negative in occipital/sensorimotor networks; subtype 2 exhibited contrasting deviations.
  • Subtypes displayed differential neural representations during empathic processing but not implicit face processing.

Conclusions:

  • MDD exhibits brain-wide, heterogeneous multilevel functional deviations.
  • The identified subtypes highlight the neurobiological complexity of MDD.
  • Findings support a personalized approach to MDD diagnosis and treatment based on identified subtypes.