Blood-based gene expression profiles models for classification of subsyndromal symptomatic depression and major depressive disorder

Abstract

Subsyndromal symptomatic depression (SSD) is a subtype of subthreshold depressive and also lead to significant psychosocial functional impairment as same as major depressive disorder (MDD). Several studies have suggested that SSD is a transitory phenomena in the depression spectrum and is thus considered a subtype of depression. However, the pathophysioloy of depression remain largely obscure and studies on SSD are limited. The present study compared the expression profile and made the classification with the leukocytes by using whole-genome cRNA microarrays among drug-free first-episode subjects with SSD, MDD, and matched controls (8 subjects in each group). Support vector machines (SVMs) were utilized for training and testing on candidate signature expression profiles from signature selection step. Firstly, we identified 63 differentially expressed SSD signatures in contrast to control (P< = 5.0E-4) and 30 differentially expressed MDD signatures in contrast to control, respectively. Then, 123 gene signatures were identified with significantly differential expression level between SSD and MDD. Secondly, in order to conduct priority selection for biomarkers for SSD and MDD together, we selected top gene signatures from each group of pair-wise comparison results, and merged the signatures together to generate better profiles used for clearly classify SSD and MDD sets in the same time. In details, we tried different combination of signatures from the three pair-wise compartmental results and finally determined 48 gene expression signatures with 100% accuracy. Our finding suggested that SSD and MDD did not exhibit the same expressed genome signature with peripheral blood leukocyte, and blood cell-derived RNA of these 48 gene models may have significant value for performing diagnostic functions and classifying SSD, MDD, and healthy controls.

Figure 1. Functional annotation of the DEGs in SSD and MDD.

(A) and (C) Pathway analysis of SSD-associated and MDD-associated genes respectively. The y-axis shows the KEGG Pathway terms, and the x-axis shows the enrichment significance P-values for the top 10 enriched Pathway terms. (B) and (D) GO analysis of SSD-associated and MDD-associated genes respectively. The y-axis shows the GO terms, and the x-axis shows the enrichment significance P-values for the top 10 enriched GO terms. Term GO:0004719 remarks the function of protein-L-isoaspartate (D-aspartate) O-methyltransferase activity. MDD: Major depression disorder; SSD: Subsyndromal symptomatic depression.

Figure 2. Biomarkers differentiation efficiency among MDD group, SDD group and HC.

(A) Complete linkage clustering analysis with 16 samples using 30 biomarkers under the criteria of adjusted.P< = 5E-4 between MDD and HC. (B) Complete linkage clustering analysis with 16 samples using 63 biomarkers under the criteria of adjusted.P< = 1E-4 between SSD and HC. (C) Complete linkage clustering analysis with 16 samples using 123 biomarkers under the criteria of adjusted.P< = 1E-4 between SSD and MDD. MDD: Major depression disorder; SSD: Subsyndromal symptomatic depression; HC: Healthy controls.