(A) Ogt mRNA levels in peripheral blood from MDD patients and healthy controls by sex. MDD patients (33 males and 37 females); healthy control subjects (38 males and 39 females). (B) Paradigms of 10 days of CSDS and SI tests. (C) C57BL/6J mice were divided into the Sus and Res subgroups according to the SI ratio after CSDS. n = 23 (control [Ctrl]); n = 22 (Sus); n = 22 (Res). (D) Ogt mRNA expression in blood from C57BL/6J mice after CSDS. (E) Relationship between Ogt levels and SI ratio, P = 0.0005. n = 12 (control); n = 7 (Sus); n = 11 (Res). (F and G) OGT protein levels in mood-related brain regions. n = 8 (Ctrl); n = 7 (Sus); n = 7 (Res) mice in the mPFC; n = 6 mice in the Stri, NAc, Hip, Amy, and DRN. (H) Relationship between OGT protein levels in the mPFC and SI, P < 0.0001. n = 8 (Ctrl); n = 7 (Sus); n = 7 (Res). (I and J) Protein O-GlcNAc levels in the mPFC after CSDS. n = 15 (Ctrl); n = 15 (Sus); n = 14 (Res) mice. (K) Pearson’s correlation analysis between total O-GlcNAc expression and SI, P = 0.0001. n = 15 (Ctrl); n = 15 (Sus); n = 14 (Res). (L and M) OGT protein expression in primary cultured astrocytes and neurons treated with DXMS. n = 5 in astrocytes; n = 4 in neurons. (N and O) OGT protein expression in primary cultured astrocytes and neurons treated with LPS. n = 7 in astrocytes; n = 5 in neurons. (P and Q) Analysis of astrocytes sorted by FACS in the mPFC following CSDS. (R and S) Astrocytic OGT expression in the mPFC after CSDS. n = 4 (Ctrl); n = 3 (Sus); n = 4 (Res) trials involving 6–8 mice each. Data are represented as mean ± SEM. Two-sided unpaired t test (M and O) or Mann-Whitney U test (A) for 2 groups; 1-way ANOVA followed by Bonferroni’s test for multiple comparisons (C, D, G, J, and S). *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001. See Supplemental Data Set 1 for statistical details.