Insula Structure Is Linked to Autonomic Cardiac Dysregulation in Depression.
Alan S R Fermin1, Hui-Ling Chan2, Masahiro Takamura3
1Center for Brain, Mind and KANSEI Sciences Research, Hiroshima University, Hiroshima, Japan; Department of Psychiatry and Neurosciences, Hiroshima University, Hiroshima, Japan.
Biological Psychiatry
|April 1, 2026
Summary
Major Depressive Disorder (MDD) is linked to reduced insula gray matter volume (GMV) and altered heart rate variability (HRV). Cardiac function may mediate this brain-heart connection in MDD patients.
Area of Science:
- Neuroscience
- Cardiology
- Psychiatry
Background:
- Major Depressive Disorder (MDD) involves mood disturbances and abnormal cardiovascular function.
- The neuroanatomical basis of cardiovascular dysfunction in MDD is not well understood.
Purpose of the Study:
- To investigate the neuroanatomical underpinnings of cardiac dysfunction in MDD.
- To examine the relationship between gray matter volume (GMV) and heart rate variability (HRV) in MDD patients and healthy controls (HC).
Main Methods:
- Magnetic resonance imaging (MRI) was used to compare GMV in brain regions regulating cardiovascular function between MDD patients (n=81) and HC (n=104).
- Photoplethysmography assessed HRV metrics during resting-state.
- Correlational and regression analyses examined the association between GMV and HRV, with mediation analyses exploring the role of GMV.
Main Results:
- MDD patients exhibited faster heart rates and reduced HRV compared to HC.
- Significantly reduced GMV was observed in the insula, ACC, hippocampus, thalamus, and cerebellum of MDD patients.
- Insula GMV was negatively correlated with HRV in HC, but not in MDD patients, suggesting a disrupted association.
Conclusions:
- A disrupted heart-brain relationship exists in MDD, characterized by a link between cardiac dysregulation and reduced insula volume.
- These findings suggest the insula and associated cardiac pathways as potential therapeutic targets for mood disorders.
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