Heart rate variability and heart rate asymmetry in adolescents with major depressive disorder during nocturnal sleep period.

Background: Although reduced heart rate variability (HRV) has been observed in adolescents with major depressive disorder (MDD), substantial between-study heterogeneity and conflicting outcomes exist. Moreover, few studies have investigated heart rate asymmetry (HRA) features despite the high sensitivity of nonlinear indices to heart rate fluctuations. This study aimed to investigate the variations in HRV measures, especially the nonlinear features of HRA, among adolescents with MDD during the nocturnal sleep period.

Methods: Adolescents with MDD and healthy controls completed the clinical assessment of depressive symptom severity and sleep quality followed by a three-night sleep electrocardiogram (ECG) monitoring. Traditional time-domain and frequency-domain HRV measures, nonlinear HRA measures, and the prevalence of different HRA forms and HRA compensation were calculated.

Results: A total of 61 participants with 154 nocturnal ECG time series were available for analysis. Vagally-mediated HRV measures, such as RMSSD, PNN50, and HF, as well as C1_d were statistically lower in clinically depressed adolescents compared with healthy controls, whereas C2_d was significantly higher. A substantial decrease in the prevalence of short-term HRA, long-term HRA, and the corresponding compensation effect were also observed. In contrast to the medium to large effect sizes observed in traditional HRV indices, nonlinear HRA features showed extremely large effect sizes in discriminating MDD (C1_d: Cohen's d= - 1.38; C2_d: Cohen's d = 1.11), and exhibited a statistical correlation with the severity of depression (C1_d: rho = - 0.269; C2_d: rho = 0.243). Moreover, there were no significant differences in the distributions of nocturnal HRA measures collected over various nights.

Conclusion: Adolescents with MDD suffered a significant decrease in vagal tone compared to healthy controls, and the features focusing on the directionality of heart rate variations may provide further information on cardiac autonomic activity associated with depression.