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Peer-reviewedCC BY-NC-ND 4.0Communications Biology

Multilevel brain heart interaction correlates with suicidal ideation in first episode drug naive major depressive disorder

  • Zhaobo Li1
  • Yuanyuan Huang2
  • Jing Zhou3,4,5
  • Minxin Guo1
  • Wei Wang1
  • Yunheng Diao1
  • Heng Zhang1
  • Tianchi Huang1,6
  • Fengchun Wu2,7,8
  • Kai Wu1,4,7,9
9 affiliations
  1. 1School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, China
  2. 2Department of Psychiatry, The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, China
  3. 3School of Materials Science and Engineering, South China University of Technology, Guangzhou, China
  4. 4National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, China
  5. 5Collaborative Innovation Center for Civil Affairs of Guangzhou, Guangzhou, China
  6. 6Guangzhou Hyper Neuron Bioscience Co., Ltd, Guangzhou, China
  7. 7Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China
  8. 8Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, China
  9. 9Department of Aging Research and Geriatric Medicine, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan
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Abstract

Emerging evidence highlights the critical role of brain-heart interaction (BHI) in regulating affective states. However, BHI alterations and their molecular underpinnings in first-episode drug-naïve (FeDn) major depressive disorder (MDD) patients with suicidal ideation (SI) remain unclear. We collected synchronized electroencephalogram (EEG) and electrocardiogram (ECG) data from 81 MDD patients with SI (MDD-SI), 55 without SI (MDD-NSI), and 82 healthy controls (HCs). An integrative framework was developed to link a multilevel EEG-ECG derived BHI index with regional gene expression. Our study reveals that MDD-SI patients exhibit a significantly lower BHI index relative to individuals with MDD-NSI and HCs, after Bonferroni correction. Alterations were localized to the ventral insula, subgenual anterior cingulate cortex, middle frontal gyrus, dorsal posterior cingulate cortex, precuneus, and rostrodorsal angular gyrus (rAG). Notably, the BHI index in the rAG was negatively correlated with depression severity (r = -0.173, corrected p = 0.039) and SI severity (r = -0.163, corrected p = 0.045). Spatial transcriptomic analysis revealed that SI-related gene expression was enriched in pathways involving metabolic regulation, synaptic function, and signal transduction. These findings demonstrate reduced BHI in MDD-SI, identify region-specific alterations, and uncover associated molecular signatures, providing insight into the clinical detection and neurobiological mechanisms of suicidal ideation in MDD.

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Cite

BibTeXRIS
BibTeX
@article{li2026multilevel,
  title = {{Multilevel brain heart interaction correlates with suicidal ideation in first episode drug naive major depressive disorder}},
  author = {Zhaobo Li and Yuanyuan Huang and Jing Zhou and Minxin Guo and Wei Wang and Yunheng Diao and Heng Zhang and Tianchi Huang and Fengchun Wu and Kai Wu},
  journal = {Communications Biology},
  year = {2026},
  month = jul,
  doi = {10.1038/s42003-026-10524-1},
  url = {https://doi.org/10.1038/s42003-026-10524-1},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Multilevel brain heart interaction correlates with suicidal ideation in first episode drug naive major depressive disorder
AU  - Zhaobo Li
AU  - Yuanyuan Huang
AU  - Jing Zhou
AU  - Minxin Guo
AU  - Wei Wang
AU  - Yunheng Diao
AU  - Heng Zhang
AU  - Tianchi Huang
AU  - Fengchun Wu
AU  - Kai Wu
PY  - 2026
DA  - 2026/07/08
JO  - Communications Biology
DO  - 10.1038/s42003-026-10524-1
UR  - https://doi.org/10.1038/s42003-026-10524-1
AB  - Emerging evidence highlights the critical role of brain-heart interaction (BHI) in regulating affective states. However, BHI alterations and their molecular underpinnings in first-episode drug-naïve (FeDn) major depressive disorder (MDD) patients with suicidal ideation (SI) remain unclear. We collected synchronized electroencephalogram (EEG) and electrocardiogram (ECG) data from 81 MDD patients with SI (MDD-SI), 55 without SI (MDD-NSI), and 82 healthy controls (HCs). An integrative framework was developed to link a multilevel EEG-ECG derived BHI index with regional gene expression. Our study reveals that MDD-SI patients exhibit a significantly lower BHI index relative to individuals with MDD-NSI and HCs, after Bonferroni correction. Alterations were localized to the ventral insula, subgenual anterior cingulate cortex, middle frontal gyrus, dorsal posterior cingulate cortex, precuneus, and rostrodorsal angular gyrus (rAG). Notably, the BHI index in the rAG was negatively correlated with depression severity (r = -0.173, corrected p = 0.039) and SI severity (r = -0.163, corrected p = 0.045). Spatial transcriptomic analysis revealed that SI-related gene expression was enriched in pathways involving metabolic regulation, synaptic function, and signal transduction. These findings demonstrate reduced BHI in MDD-SI, identify region-specific alterations, and uncover associated molecular signatures, providing insight into the clinical detection and neurobiological mechanisms of suicidal ideation in MDD.
SN  - 2399-3642
ER  -