Identifying Physiological and Cognitive Indicators of Subthreshold Depression and Major Depressive Disorder Progression Risk

Purpose: Subthreshold depression (StD), depressive symptoms below the diagnostic threshold for major depressive disorder (MDD), is associated with functional impairment and increased risk of MDD onset, but its physiological and cognitive characteristics remain unclear. This study aimed to identify objective markers of StD and validate predictive factors for MDD onset. Patients and Methods: Among 168 university students, participants were classified into a StD group (n=87) and a healthy control group (n=81) using the Beck Depression Inventory-II (BDI-II). The StD group was further subdivided into “low depression” (BDI-II < 10, n = 21) and “maintained depression” (BDI-II ≥ 10, n = 66) based on their BDI-II scores at baseline. Assessments included voice characteristics, heart rate variability (HRV), peripheral body temperature, emotion recognition, and neurocognitive tasks. Between-group differences were tested using ANOVA and MANOVA, and participants were followed for MDD onset at 3-month intervals until March 2024. Results: Compared to controls, the StD group showed increased vocal arousal (p = 0.007), elevated peripheral body temperature (p < 0.001), and reduced low-frequency HRV (p = 0.018). Sustained attention and executive function were impaired (p < 0.05). Accuracy in emotion recognition was lower for happy and surprised expressions (p = 0.030; p = 0.038). Subgroup analysis revealed more pronounced impairments in HRV, executive function, and emotion recognition in the maintained depression subgroup, which also had a higher MDD incidence (7 cases). In contrast, the low depression group showed selective attentional deficits and impaired emotion recognition, but no MDD onset. Conclusion: StD correlates with physiological and cognitive abnormalities reflecting MDD, and persistent symptoms suggest increased progression risk. These findings present candidate markers (voice arousal, HRV, body temperature, emotion recognition) for early identification and risk stratification; however, conclusions should be interpreted cautiously given the exploratory design.