Research Paper Volume 13, Issue 9 pp 13124—13137

Gene expression signatures differentiating major depressive disorder from subsyndromal symptomatic depression

Guoqin Hu1,2, , Shunying Yu1, , Chengmei Yuan1, , Wu Hong1, , Zuowei Wang3, , Ran Zhang1, , Dongxiang Wang1, , Zezhi Li4, , Zhenghui Yi1, , Yiru Fang1,5,6, ,

  • 1 Clinical Research Center, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
  • 2 Department of Psychiatry, Huangpu District Mental Health Center, Shanghai 200023, China
  • 3 Department of Psychiatry, Hongkou District Mental Health Center, Shanghai 200083, China
  • 4 Department of Neurology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
  • 5 CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai 20000, China
  • 6 Shanghai Key Laboratory of Psychotic Disorders, Shanghai 201108, China

Received: November 19, 2020       Accepted: March 27, 2021       Published: May 8, 2021
How to Cite

Copyright: © 2021 Hu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Subsyndromal symptomatic depression (SSD) and major depressive disorder (MDD) have been classified as distinct diseases, due to their dissimilar gene expression profiles and responses to venlafaxine. To identify specific biomarkers of these two diseases, we conducted a secondary analysis of the gene expression signatures of SSD patients, MDD patients and healthy controls (n=8/group) from the study of Yi et al. Global, individual, specific, enrichment and co-expression analyses were used to compare the transcriptomic profiles of peripheral blood lymphocytes from the three groups. The global and individual analyses revealed that different genes were up- and downregulated in the SSD and MDD groups. Through our specific analysis, we identified 1719 and 3278 differentially expressed genes specifically associated with MDD and SSD, respectively. Enrichment and co-expression analyses demonstrated that the genes specific to MDD were enriched in pathways associated with hormone levels and immune responses, while those specific to SSD were associated with immune function. The specific hub gene for the MDD co-expression network was transmembrane protein 132B (TMEM132B), while the hub genes for SSD were actin-related protein 2/3 complex (ARPC2) and solute carrier family 5 member 5 (SLC5A5). This bioinformatic analysis has provided potential biomarkers that can distinguish SSD from MDD.


DEGs: differentially expressed genes; FREM3: FRAS1-related extracellular matrix 3; HC: healthy control; HRSD-17: the 17-item Hamilton Rating Scale for Depression; KEGG: Kyoto Encyclopedia of Genes and Genomes; MDD: major depressive disorder; SSD: subsyndromal symptomatic depression.