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Updated: Jun 9, 2025

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Exploring causal association between functional/structural connectivity and major depression disorder: A

Huacong Liu1, Zhenyi Lai1, Yumeng Huang2

  • 1School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong Province, China.

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Summary

This study used Mendelian randomization to find causal links between brain network connectivity and major depressive disorder (MDD). Specific brain network connectivity patterns, like in the dorsal attention and limbic networks, increase MDD risk.

Keywords:
Functional connectivityMajor depression disorderMendelian randomizationResting-state networksStructural connectivity

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Genetics

Background:

  • Major depressive disorder (MDD) is linked to brain network communication issues.
  • Previous studies suggest correlations, but causal links between brain connectivity and MDD remain unclear.

Purpose of the Study:

  • To investigate the potential causal relationship between functional connectivity (FC) and structural connectivity (SC) within resting-state brain networks (RSNs) and MDD using Mendelian randomization (MR).

Main Methods:

  • A two-sample bidirectional MR analysis was performed.
  • Inverse variance weighted (IVW) method was used to assess causality between FC/SC and MDD.
  • Sensitivity analyses were conducted using methods like MR-Egger.

Main Results:

  • Increased dorsal attention network FC, limbic network SC, and dorsal attention network SC were associated with higher MDD risk.
  • Reverse MR analysis indicated that higher MDD risk was linked to reduced frontal parietal network FC.

Conclusions:

  • This study provides evidence for a causal relationship between specific RSN FC/SC and MDD risk.
  • Abnormalities in dorsal attention network FC/SC and limbic network SC are identified as risk factors for MDD.
  • Frontal parietal network FC abnormalities may be a consequence of MDD onset, warranting further investigation for neuroimaging markers in prevention and treatment.