To analyze using data mining the differential molecular expression of transcriptome in the dorsal lateral prefrontal cortex (DLPFC) in bipolar disorder (BD) and depression, and to analyze the differential gene correlation pathways in the two disorders and their relationship with immunity and metabolism. Methods: Using "bipolar disorder", "depression", and "sequencing" as keywords, the GEO (Gene Expression Omnibus) database was searched. The DLPFC transcriptome data of 6 controls and 7 BD patients and 29 controls and 30 depression patients were extracted from the gene bank; the peripheral blood transcriptome data of 240 healthy controls and 240 BD patients were calculated using DESeq2 software. Based on the Biological Process (BP), GO function analysis, differential analysis, and intersection analysis were used to analyze the differential gene-related pathways of the two diseases and their relationship with immunity and metabolism. Results: There were 384 significantly overexpressed genes and 117 significantly underexpressed genes in the DLPFC brain region of BD patients. A total of 165 genes were significantly overexpressed and 316 genes were significantly underexpressed in the DLPFC brain region of depression patients. It was found that the brain regions of both BD patients and depression patients had neurological abnormalities compared with normal controls; depression was mostly enriched in immune-inflammation-related pathways, and BD was mostly enriched in metabolism-related pathways. The results of gene intersection showed that there were 74 immune-related genes and 20 metabolism-related genes in the differential genes of depression patients, while there were 42 immune-related genes and 51 metabolism-related genes in the differential genes of BD patients. There were 51 differential genes related to metabolism in the DLPFC brain region and peripheral blood of BD patients. The peripheral blood transcriptome data verified that the metabolic pathway enrichment results showed abnormalities in fatty acid biosynthesis, ubiquinone and other terpenoid biosynthesis, selenium compound metabolism, degradation of other glycans, and biosynthesis of other O-glycan types. Conclusion: The results of DLPFC transcriptome suggest that the two mental diseases have different proportions of abnormalities in genes related to immune and metabolic functions. Depression is prone to immune-related abnormalities, and BD is more prone to metabolic abnormalities.