Insula structure is linked to autonomic cardiac dysregulation in depression

BackgroundMajor Depressive Disorder (MDD), characterized primarily by mood disturbances, is also accompanied by abnormal cardiovascular functioning.However, the neuroanatomical substrates underlying this cardiovascular dysfunction remain elusive. MethodsThis study investigated the neuroanatomical foundations of cardiac dysfunction in MDD.Using magnetic resonance imaging, we examined differences in gray matter volume (GMV) between MDD patients (n = 81) and healthy controls (HC, n = 104) in regions implicated in cardiovascular regulation, notably the insula, anterior cingulate cortex (ACC), thalamus, and brainstem nuclei.Photoplethysmography signals acquired during a 10-minute resting-state provided data to investigate group differences in heart (pulse) rate variability (HRV) metrics (e.g.heart rate, low and high frequency components).Correlations and mixed-effect linear regression models tested the strength of group differences in the association between HRV metrics and regional GMV.Mediation analyses evaluated whether GMV mediated the observed group differences in HRV. ResultsPatients with MDD had faster heart rates, and reduced HRV, when compared to HCs.Neuroanatomically, patients with MDD manifest significantly reduced GMV across the insula, ACC, hippocampus, thalamus, and cerebellum.Negative correlations between insula GMV and HRV metrics were found in HCs, but not in MDD patients.Regression models confirmed stronger association between insula volume and HRV metrics in HCs.Mediation analyses revealed that differences in cardiac measures explain the reduced insula GMV differences between diagnostic groups. ConclusionsThese findings reveal a disrupted heart-brain relationship in MDD, notably a link between cardiac dysregulation and reduced insula volume.This highlights the importance of potential body-brain targets for therapeutic intervention in mood disorders.