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Background Subsyndromal symptomatic depression(SSD),as a transitory phenomenon of depres-sion spectrum,was considered as an important subtype of depression.However,only few studies explored the molecular mechanisms and the pathophysiology of SSD.Recently,the relationship between SSD and major depressive disorder(MDD)has been received the growing attractions.In this study,we compared the gene expression profiling signatures between SSD and MDD using the mRNA microarray.Methods Three groups including the drug-free first-episode sub-jects with SSD,MDD,and matched controls were classified and each group contains 8 subjects.The global analysis,in-dividual analysis,Venn diagrams and functional enrichment analysis were performed to compare the transcriptomic pro-files in peripheral blood lymphocytes among three groups.Venn Diagrams analysis and gene ontology analysis were per-formed with"Venndiagram"and"topGO"package on the R platform.Results Firstly,global analysis identified 9427 differentially expressed genes(DEGs)in the SSD vs Control,4125 DEGs in the MDD vs Control and 9262 DEGs in the MDD vs SSD(p-value<0.05).Several interesting genes,including EDNRB(fold change =8.17 in MDD vs SSD),AHNAK(fold change = 12.01in MDD vs SSD),LOC284701(fold change = 7.06 in MDD vs SSD),etc,achieved strik-ing changes in the individual analysis of three comparisons.Venn diagram analysis identified 1719 DEGs,3278 DEGs and 3269 DEGs were specifically associated with comparison of MDD vs Control,SSD vs Control and MDD vs SSD,re-spectively.Interestingly,gene ontology analysis revealed that the term of"developmental process","single-multicellular organism process"and"system development"were significantly enriched into the comparison of MDD vs Control while the term"cell adhesion","biological process" and"single-organism cellular"were significantly associated with the development of SSD.Conclusion The specific analyses revealed no apparent similarities between the differential regu-latory processes underlying MDD and SSD.This bioinformatic analysis may provide valuable target terms that maybe re-sponsible for the disease transitory from SSD to MDD.