title: Clinical variations modulate patterns of gene expression and define blood biomarkers in major depression.
abstract: The aim of the study is to compare the expression level of candidate genes between patients suffering from a severe major depressive episode (MDE) and controls, and also among patients during MDE evolution. After a comprehensive review of the biological data related to mood disorders, we initiated a hypothesis-driven exploration of candidate mRNAs. Using RT-qPCR, we analyzed peripheral blood mononuclear cells (PBMCs) mRNA obtained from a homogeneous population of 11 patients who suffered from severe melancholic MDE. To assess the evolution of MDE, we analyzed PBMC mRNAs that were collected on Day 1 and 8 weeks later. Data from these patient samples were analyzed in comparison to age- and sex-matched healthy controls. Among 40 candidate genes consistently transcribed in PBMCs, 10 were differentially expressed in at least one comparison. We found that variations of mRNA levels for NRG1, SORT1 and TPH1 were interesting state-dependent biological markers of the disease. We also observed that variations in other mRNA expression were associated with treatment efficacy or clinical improvement (CREB1, HDAC5, HSPA2, HTR1B, HTR2A, and SLC6A4/5HTT). Significantly, 5HTT exhibited a strong correlation with clinical score evolution. We also found a state-independent marker, IL10. Moreover, the analysis of 2 separate MDEs concerning a same patient revealed comparable results for the expression of CREB1, HSPA2, HTR1B, NRG1 and TPH1. Overall, our results indicate that PBMCs obtained at different time points during MDE progression represent a promising avenue to discover biological markers for depression.
authors.affiliation: NICN-CNRS UMR 6184, Faculté de Médecine Nord-IFR Jean Roche, 51 Bd Pierre Dramard, 13344 Marseille Cedex 15, France.
authors.forename: Raoul
authors.initials: R
authors.lastname: Belzeaux
authors.forename: Christine
authors.initials: C
authors.lastname: Formisano-Tréziny
authors.forename: Anderson
authors.initials: A
authors.lastname: Loundou
authors.forename: Laurent
authors.initials: L
authors.lastname: Boyer
authors.forename: Jean
authors.initials: J
authors.lastname: Gabert
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Samuelian
authors.forename: François
authors.initials: F
authors.lastname: Féron
authors.forename: Jean
authors.initials: J
authors.lastname: Naudin
authors.forename: El Chérif
authors.initials: EC
authors.lastname: Ibrahim
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D000368:Aged; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000097:blood / Q000235:genetics / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism; D011569:Psychiatric Status Rating Scales; D012333:RNA, Messenger / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D018709:Statistics, Nonparametric; D013997:Time Factors; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000928:Antidepressive Agents; D015415:Biomarkers; D016753:Interleukin-10; D020890:Neuregulin-1; D012333:RNA, Messenger; D050486:Serotonin Plasma Membrane Transport Proteins; D014365:Tryptophan Hydroxylase; D000099183:Sortilin; C508609:IL10 protein, human; C094131:NRG1 protein, human; C493230:SLC6A4 protein, human; C497467:TPH1 protein, human