Fig. 3: Differential biomarker–behavior correlations in individuals with MDD and NC.

Compared with the NC, participants in the MDD group exhibited a more pronounced association between blood amyloid levels and depression tendency, as indicated by the positive association of plasma Aβ40 with HADS-D (group difference p = 0.005; A left) and the negative association of the Aβ42/Aβ40 ratio with HADS-D (group difference p = 0.005; A right). Furthermore, the associations between biomarkers and cognition in the MDD group differed from those in the NC, showing a stronger positive association between plasma Aβ42 and facial recognition (FMT, p = 0.034; B left-upper) and a stronger negative association between the Tau/Aβ42 ratio and cognitive processing in coding compared with NC individuals (DSST, p = 0.030; B right-upper). Additionally, higher plasma GFAP levels were associated with poorer cognitive performance in MoCA (p = 0.039; B left-lower) and DSST (p = 0.012; B right-lower), an association not observed in NC participants. Notably, MDD participants engaging in more physical activity, indicated by a higher metabolic equivalent, exhibited higher plasma p-Tau181 levels (p = 0.014; C left) and a higher p-Tau181/Aβ42 ratio (p = 0.011; C right). Moreover, plasma biomarkers did not exhibit differential associations with total PFS mental and physical fatigue scores between the MDD and NC groups.