Sensitivity to stress is essential in the onset, clinical symptoms, course, and prognosis of major depressive disorder (MDD). Meanwhile, it was unclear how variously classified but connected stress-sensitivity variables affect MDD. We hypothesize that high-level trait- and state-related stress-sensitivity factors may have different cumulative effects on the clinical symptoms and follow-up outcomes of MDD.

To investigate how stress-sensitivity factors added up and affected MDD clinical symptoms and follow-up results.

In this prospective study, 281 MDD patients were enrolled from a tertiary care setting. High-level stress-sensitivity factors were classified as trait anxiety, state anxiety, perceived stress, and neuroticism, with a total score in the top quartile of the research cohort. The cumulative effects of stress-sensitivity factors on cognitive dysfunction, disability and functional impairment, suicide risk, and depressive and anxiety symptoms were examined using an analysis of variance with linear trend analysis. Correlations were investigated further using multiple regression analysis.

Regarding high-level stress-sensitivity factors, 53.40% of patients had at least one at baseline, and 29.61% had two or more. Four high-level stress-sensitivity components had significant cumulative impacts on MDD symptoms at baseline (all P < 0.001). Perceived stress predicted the greatest effect sizes of state-related factors on depressive symptoms (partial η 2 = 0.153; standardized β = 0.195; P < 0.05). The follow-up outcomes were significantly impacted only by the high-level trait-related components, mainly when it came to depressive symptoms and suicide risk, which were predicted by trait anxiety and neuroticism, respectively (partial η 2 = 0.204 and 0.156; standardized β = 0.247 and 0.392; P < 0.05).

To enhance outcomes of MDD and lower the suicide risk, screening for stress-sensitivity factors and considering multifaceted measures, mainly focusing on trait-related ones, should be addressed clinically.