*3.6. Relationship between Plasma Proteins and Psychiatric Morbidity Survey Scores*

Because MADRS score is the standard criterion for determining response to drug administration, plasma proteins with high positive or negative correlation with MADRS scores indirectly reflect the efficacy of the drug. Using Spearman's correlation analysis of 316 quantified proteins, we determined the significant correlation relationship between the abundance of the 64 identified plasma proteins and at least one other psychiatric index, such as CGI-S, BDI, HAM-D, CUDOS, and psychological quality of life (PsychoQOL) scores by permutation-based analysis (Supplementary Table S5). Each of these 11 proteins, EXT1, PROC, NUCB1, PROS1, LYVE1, F9, ATRN, HRG, FUCA1, CD109 and ANGPTL6, significantly correlated with two or more of the psychiatric indices (adjusted *p*-value < 0.05; Figure 5).

**Figure 5.** Plots showing correlations between the abundance of 11 plasma proteins and psychological indices; these 11 proteins correlated significantly with two or more of the six indices. Positive and negative correlation coefficients are colored blue and red, respectively, with the size of the bubble indicating the minus log10 adjusted *p-*value, and the dotted circles indicating significant correlation relationships (adjusted *p*-value < 0.05).
