Fig. 4: RNA expression and intron retention ratios are restored by ketamine treatment.

A Venn diagram comparing genes whose RNA expression was upregulated in TRD patients and downregulated by ketamine treatment (reverse V shape). The left panel shows nonresponders, the right panel shows responders, and the gene symbols indicate overlapping (recovered) genes. Bold indicates genes related to innate immunity. B Venn diagram comparing genes whose RNA expression was downregulated in TRD patients and upregulated by ketamine treatment (V shape). C (i) Box and whisker plots showing the relative IR ratios of the 65 IncIR loci (pretreatment) in nonresponders and these loci after ketamine treatment. (ii) Box and whisker plot showing the relative IR ratios of the 145 DecIR loci (pretreatment) in nonresponders and those loci after ketamine treatment. D (i) The 45 IncIR loci in responders. (ii) The 98 DecIR loci in responders. E Venn diagram comparing genes whose IR ratio was increased (IncIR) in TRD patients and decreased (DecIR) by ketamine treatment (reverse V shape). The left panel shows nonresponders, the right panel shows responders, and the gene symbols indicate overlapping (recovered) genes. Bold indicates genes related to innate immunity. F Venn diagram comparing genes whose IR ratio is decreased (DecIR) in TRD patients and increased (IncIR) by ketamine treatment (V shape). The left panel shows the nonresponder case, the right panel shows the responder case, and the gene symbols indicate overlapping (recovered) genes. Bold indicates genes related to innate immunity. G Heatmap showing sites with recovered intron ratios. Relative intron retention ratios are indicated by z scores. (i) Recovery of IR loci (60 loci) in the nonresponder group. (ii) Recovery of IR loci (26 loci) in the responder group. H GO enrichment analysis of the recovered IR genes. The horizontal axis indicates −log₁₀ p values. The dark blue bars are GO terms with p values < 0.05, and the light blue bars are those with no significant difference. Gene symbols indicate genes related to innate immunity. (i) Fifty-eight genes, including the 60 recovered IR loci in nonresponders, were used. (ii) Twenty-six genes, including the 26 recovered IR loci in responders, were used.