Cardiac Clues in Major Depressive Disorder: Evaluating Electrical Risk Score as a Predictive Electrocardiography Biomarker

Abstract

Background and Objectives: Major depressive disorder (MDD) is a prevalent psychiatric illness increasingly recognized as a systemic condition with implications for cardiovascular diseases. Growing evidence indicates that individuals with MDD have an elevated risk of cardiovascular mortality, underscoring the need for reliable, non-invasive biomarkers to assess cardiac risk. While underlying mechanisms remain unclear, electrocardiogram (ECG)-based markers offer a promising, non-invasive means of evaluation. Among these, the electrical risk score (ERS), a composite derived from specific ECG parameters, has emerged as a predictor of adverse cardiac outcomes. This study aimed to investigate the association between ERS and MDD, and whether ERS correlates with depression severity and illness duration. Materials and Methods: In this retrospective cross-sectional study, 12-lead ECGs were evaluated to calculate the ERS based on six ECG parameters: heart rate, corrected QT interval, Tp-e interval, frontal QRS-T angle, QRS transition zone, and presence of left ventricular hypertrophy according to Sokolow-Lyon criteria. The Hamilton Depression Rating Scale (HAM-D) was utilized. Results: The study included 102 patients with MDD and 62 healthy controls. No significant differences were observed in baseline or laboratory parameters between the groups. However, heart rate, Tp-e interval, frontal QRS-T angle, and ERS were significantly higher in the depression group. ROC analysis identified ERS as the strongest predictor of depression. ERS was significantly higher in patients with severe depression compared to those with mild symptoms and showed a positive correlation with both disease duration and HAM-D score. Conclusions: Here, we show that the ECG-derived ERS is significantly elevated in patients with MDD and is associated with increased cardiac risk. ERS outperformed conventional ECG parameters in identifying individuals with depression and demonstrated positive associations with both illness duration and symptom severity. These findings suggest that ERS may serve as a practical, non-invasive biomarker for assessing cardiovascular vulnerability in this population.

Keywords: biomarkers; cardiovascular diseases; electrical risk score; electrocardiography; heart rate; major depressive disorder; risk assessment.

Figure 1

An example of the evaluation of ERS from the 12-lead ECG with its automatic report.

Figure 2

Comparison of the AUC values of the electrocardiographic parameters for predicting the presence of depression.

Figure 3

Comparison of ERSs among the patients with mild, moderate, and severe HAM-D scores.

Figure 4

Correlation analysis of ERS with duration of the disease (A) and HAM-D scale (B). Circles indicate data points, and lines represent the correlation line.