Fig. 1: Expression of FTO is decreased in the hippocampus of MDD patients and mouse models of depression.

a Microarray analysis of the genes encoding m6A-modifying enzymes in the peripheral blood of humans. Ctl, n = 20; major depressive disorder (MDD), n = 36. METTL3, p < 0.000001; METTL14, p < 0.000001; WTAP, p < 0.000001; ALKBH5, p < 0.000001; FTO, p = 0.000054. b Real-time quantitative PCR (qPCR) analysis of the genes encoding m6A-modifying enzymes in the peripheral blood of humans. Ctl, n = 50; MDD, n = 50. METTL3, p = 0.000755; METTL14, p = 0.000116; WTAP, p = 0.005480; ALKBH5, p < 0.000001; FTO, p = 0.000007. c mRNA expression of m6A-modifying enzymes in the peripheral blood of mice, n = 6 per group. UCMS, chronic unpredictable mild stress. Mettl3, p = 0.599250; Mettl14, p = 0.601975; Wtap, p = 0.614743; Alkbh5, p = 0.007390; FTO, p = 0.028276. d, e Forced swimming test (FST) and sucrose consumption test (SCT) in the UCMS mouse model. Ctl, n = 8; UCMS, n = 18. d p = 0.0432; e p < 0.0001. f Expression of hippocampal FTO mRNA in the UCMS model. n = 8 per group. p = 0.0182. g Expression of hippocampal FTO protein in the UCMS model. n = 3 per group. p = 0.0455. The samples derived from the same experiment and that blots were processed in parallel. h, i FST and SCT in the chronic restraint stress (CRS) mouse model. n = 8 per group. h p = 0.0007; i p = 0.03. j Expression of hippocampal FTO mRNA in the CRS model. Ctl, n = 3; CRS, n = 4. p = 0.037. k Expression of hippocampal FTO protein in the CRS model. n = 4 per group. p = 0.0005. l, m FST and social interaction test (SIT) in the social defeat stress (SDS) mouse model. Ctl, n = 11; SDS, n = 15. l p = 0.0004; m p < 0.0001. n Expression of hippocampal FTO mRNA in the SDS model. n = 4 per group. p = 0.0008. o Expression of hippocampal Fto protein in the SDS model. Ctl, n = 3; SDS, n = 4. p < 0.0001. p mRNA expression of m6A-modifying enzymes in the hippocampus of MDD patients. n = 3 per group. METTL3, p = 0.990981; METTL14, p = 0686706; WTAP, p = 0.565588; ALKBH5, p = 0.095860; FTO, p = 0.031700. *p < 0.05, **p < 0.01, ***p < 0.001. Two-tailed student’s t-test. Adjustments were made for multiple comparisons test. Error bars represent s.e.m. Source data are provided as a Source Data file.