Divergence of clinical and autonomic recovery in adolescent major depressive disorder: A 10-week prospective heart rate variability study with nocturnal electrocardiogram monitoring

BACKGROUND: Adolescence is a critical window for autonomic nervous system (ANS) development, which can be disrupted by major depressive disorder (MDD). Heart rate variability (HRV) is a promising biomarker, but adolescent findings are inconsistent with scarce longitudinal treatment data. This study longitudinally assessed autonomic function in adolescents with MDD via nocturnal electrocardiogram (ECG). METHODS: We enrolled 43 adolescents aged 12-18 years with MDD and 43 healthy controls. MDD participants received routine, non-study-mandated selective serotonin reuptake inhibitors (SSRIs) treatment, and completed 3 consecutive nights of nocturnal ECG monitoring at both baseline and 10-week post-treatment follow-up. Controls completed only the baseline monitoring protocol. We performed between-group, pre-post within-MDD group, and correlation analyses between HRV and clinical features. RESULTS: 10-week treatment significantly reduced 17-item Hamilton Depression Rating Scale (HAMD-17) and Hamilton Anxiety Rating Scale (HAMA) scores, though only 7.0% of patients achieved early clinical response. Baseline HRV deficits in MDD persisted post-treatment, with no reversal of autonomic impairment and further pathological sympathetic predominance. Notably, somatic anxiety reduction was negatively correlated with post-treatment low-frequency/high-frequency ratio (LF/HF) and normalized low-frequency power (LFn) (P < 0.05), indicating mitigation of sympathetic pathological deterioration rather than autonomic normalization. CONCLUSION: This study shows dissociation between partial clinical improvement and persistent autonomic dysfunction in adolescent MDD. HRV may be a useful adjunct biomarker, and somatic anxiety-targeted interventions may facilitate recovery.