Stress reactivity of the autonomic nervous system in youth with and without major depressive disorder.

UNLABELLED: Altered Autonomic Nervous System (ANS) function has been described in youth with Major Depressive Disorder (MDD), but studies are scarce and rarely consider sex, nor both parasympathetic and sympathetic ANS measures. Stress regulation plays a key role in the emergence and maintenance of MDD. Here, we aimed to investigate ANS stress reactivity within a clinical sample of female and male youth with MDD compared to healthy controls (HCs). Parasympathetic and sympathetic ANS stress reactivity (Heart Rate, HR; Respiratory Heart Rate Variability, RespHRV; Pre-ejection Period, PEP) was studied in response to a standardized psychosocial stress task (Trier Social Stress Test) in n = 100 youth with MDD (60% female; 12–18 years), and n = 70 HCs, while controlling for relevant confounders (e.g., age, puberty). Besides higher levels of self-reported psychological stress, youth with MDD showed lower HR increase, lower parasympathetic (less increase of RespHRV), and lower sympathetic (less reduction of PEP) ANS stress response compared to HCs. No effects of sex were found. Findings indicate blunted parasympathetic and sympathetic ANS stress responses contrasting stronger psychological stress experience in both female and male youth with MDD compared to HCs. This altered psychophysiological stress response may provide valuable insights for the development and optimization of future diagnostic and therapeutic approaches for youth with MDD. Further studies are needed to investigate the underlying biological backgrounds and longitudinal trajectories to understand the influence on stress regulation on onset and remission of MDD.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00787-026-02998-5.