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Background <p>Bipolar disorder (BD) is a highly heritable condition characterized by recurrent shifts between manic and depressive states. Here we investigated the potential involvement of the habenula because it plays a central role in negative affect and behavioral regulation.</p> Methods <p>We investigated bilateral habenular volume and seed-based resting-state functional connectivity in a discovery cohort (78 BD, 102 controls) and an independent replication cohort (72 BD, 85 controls). Associations among habenular features, clinical symptoms, and molecular correlates were examined by integrating pathway-specific polygenic risk scores and brain-wide gene expression data from the Allen Human Brain Atlas.</p> Results <p>Across both cohorts, BD was associated with reduced bilateral habenular volume and increased rs-FC between the habenula and right precentral gyrus. Habenular volume correlated positively with severity of mania symptoms and negatively with severity of symptoms of anxiety and somatization. Polygenic risk scores linked the altered volume to dopaminergic pathways and altered connectivity to serotonergic pathways, while transcriptomic data linked the altered connectivity to changes in expression of synaptic membrane structures, transporter complexes, and other proteins involved in synaptic transmission.</p> Conclusions <p>Structural, functional and transcriptomic data identify the habenula as a critical neural hub in BD and therefore important for understanding pathogenesis and clinical manifestations.</p> Clinical trial number <p>Not applicable.</p>

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Habenular structural–functional dysconnectivity in bipolar disorder: evidence from multimodal imaging and transcriptomic integration

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月30日

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  • Meng-Xuan Qiao,
  • Wei Wei,
  • Meng Zhou,
  • Ming-li Li,
  • Ya-min Zhang,
  • Xiao-Jing Li,
  • Wei Deng,
  • Wan-Jun Guo,
  • Qiang Wang,
  • Hua Yu,
  • Tao Li

摘要

Background

Bipolar disorder (BD) is a highly heritable condition characterized by recurrent shifts between manic and depressive states. Here we investigated the potential involvement of the habenula because it plays a central role in negative affect and behavioral regulation.

Methods

We investigated bilateral habenular volume and seed-based resting-state functional connectivity in a discovery cohort (78 BD, 102 controls) and an independent replication cohort (72 BD, 85 controls). Associations among habenular features, clinical symptoms, and molecular correlates were examined by integrating pathway-specific polygenic risk scores and brain-wide gene expression data from the Allen Human Brain Atlas.

Results

Across both cohorts, BD was associated with reduced bilateral habenular volume and increased rs-FC between the habenula and right precentral gyrus. Habenular volume correlated positively with severity of mania symptoms and negatively with severity of symptoms of anxiety and somatization. Polygenic risk scores linked the altered volume to dopaminergic pathways and altered connectivity to serotonergic pathways, while transcriptomic data linked the altered connectivity to changes in expression of synaptic membrane structures, transporter complexes, and other proteins involved in synaptic transmission.

Conclusions

Structural, functional and transcriptomic data identify the habenula as a critical neural hub in BD and therefore important for understanding pathogenesis and clinical manifestations.

Clinical trial number

Not applicable.