Responder and nonresponder patients exhibit different peripheral transcriptional signatures during major depressive episode

被引:201
作者
Belzeaux, R. [1 ,2 ,3 ]
Bergon, A. [2 ,4 ,5 ]
Jeanjean, V. [1 ,2 ]
Loriod, B. [4 ,5 ]
Formisano-Treziny, C. [6 ,7 ]
Verrier, L. [2 ]
Loundou, A. [8 ,9 ]
Baumstarck-Barrau, K. [8 ,9 ]
Boyer, L. [9 ,10 ]
Gall, V. [4 ,5 ]
Gabert, J. [6 ,7 ,11 ]
Nguyen, C. [4 ,5 ]
Azorin, J-M [2 ,3 ]
Naudin, J. [2 ]
Ibrahim, E. C. [1 ]
机构
[1] Aix Marseille Univ, CNRS, CRN2M UMR 7286, F-13344 Marseille 15, France
[2] Pole Psychiat Univ Solaris, Hop St Marguerite, APHM, Marseille, France
[3] Fdn Rech & Soins Sante Mentale, FondaMental, Paris, France
[4] INSERM, TAGC UMR S 1090, F-13258 Marseille, France
[5] Aix Marseille Univ, TAGC UMR S 1090, F-13344 Marseille 15, France
[6] INSERM, UNIS UMR S 1072, F-13258 Marseille, France
[7] Aix Marseille Univ, UNIS UMR S 1072, F-13344 Marseille 15, France
[8] Aix Marseille Univ, Unite Aide Methodol, F-13344 Marseille 15, France
[9] Hop Enfants La Timone, APHM, Dept Publ Hlth, Marseille, France
[10] Aix Marseille Univ, Res Unit EA 3279, F-13344 Marseille 15, France
[11] Hop Nord Marseille, APHM, Lab Biochim Biol Mol, Marseille, France
关键词
antidepressant; biomarker; miRNA; mood disorder; PBMC; transcriptome; GENE-EXPRESSION PROFILES; BLOOD MONONUCLEAR-CELLS; PREFRONTAL CORTEX; BIPOLAR DISORDER; ANTIDEPRESSANT TREATMENT; MICRORNA EXPRESSION; ALTERED EXPRESSION; ABERRANT EXPRESSION; POSTMORTEM BRAINS; GROWTH-FACTOR;
D O I
10.1038/tp.2012.112
中图分类号
R749 [精神病学];
学科分类号
100204 [神经病学];
摘要
To date, it remains impossible to guarantee that short-term treatment given to a patient suffering from a major depressive episode (MDE) will improve long-term efficacy. Objective biological measurements and biomarkers that could help in predicting the clinical evolution of MDE are still warranted. To better understand the reason nearly half of MDE patients respond poorly to current antidepressive treatments, we examined the gene expression profile of peripheral blood samples collected from 16 severe MDE patients and 13 matched controls. Using a naturalistic and longitudinal design, we ascertained mRNA and microRNA (miRNA) expression at baseline, 2 and 8 weeks later. On a genome-wide scale, we detected transcripts with roles in various biological processes as significantly dysregulated between MDE patients and controls, notably those involved in nucleotide binding and chromatin assembly. We also established putative interactions between dysregulated mRNAs and miRNAs that may contribute to MDE physiopathology. We selected a set of mRNA candidates for quantitative reverse transcriptase PCR (RT-qPCR) to validate that the transcriptional signatures observed in responders is different from nonresponders. Furthermore, we identified a combination of four mRNAs (PPT1, TNF, IL1B and HIST1H1E) that could be predictive of treatment response. Altogether, these results highlight the importance of studies investigating the tight relationship between peripheral transcriptional changes and the dynamic clinical progression of MDE patients to provide biomarkers of MDE evolution and prognosis.
引用
收藏
页码:e185 / e185
页数:12
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