lunes, 30 de abril de 2012

Translational Psychiatry - Discovery of blood transcriptomic markers for depression in animal models and pilot validation in subjects with early-onset major depression

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Translational Psychiatry - Discovery of blood transcriptomic markers for depression in animal models and pilot validation in subjects with early-onset major depression

Original Article

Citation: Translational Psychiatry (2012) 2, e101; doi:10.1038/tp.2012.26
Published online 17 April 2012

Discovery of blood transcriptomic markers for depression in animal models and pilot validation in subjects with early-onset major depression

K Pajer1,5, B M Andrus2,5, W Gardner1,3, A Lourie3, B Strange3, J Campo3, J Bridge3, K Blizinsky2, K Dennis2, P Vedell4, G A Churchill4 and E E Redei2,5
  1. 1Department of Psychiatry, Dalhousie University Faculty of Medicine
  2. 2Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
  3. 3Department of Pediatrics, Ohio State University College of Medicine, Columbus, OH, USA
  4. 4The Jackson Laboratory, Bar Harbor, ME, USA
Correspondence: Dr EE Redei, Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. E-mail: e-redei@northwestern.edu
5These two authors contributed equally to this work.
Received 20 January 2012; Revised 29 February 2012; Accepted 3 March 2012
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Abstract

Early-onset major depressive disorder (MDD) is a serious and prevalent psychiatric illness in adolescents and young adults. Current treatments are not optimally effective. Biological markers of early-onset MDD could increase diagnostic specificity, but no such biomarker exists. Our innovative approach to biomarker discovery for early-onset MDD combined results from genome-wide transcriptomic profiles in the blood of two animal models of depression, representing the genetic and the environmental, stress-related, etiology of MDD. We carried out unbiased analyses of this combined set of 26 candidate blood transcriptomic markers in a sample of 15–19-year-old subjects with MDD (N=14) and subjects with no disorder (ND, N=14). A panel of 11 blood markers differentiated participants with early-onset MDD from the ND group. Additionally, a separate but partially overlapping panel of 18 transcripts distinguished subjects with MDD with or without comorbid anxiety. Four transcripts, discovered from the chronic stress animal model, correlated with maltreatment scores in youths. These pilot data suggest that our approach can lead to clinically valid diagnostic panels of blood transcripts for early-onset MDD, which could reduce diagnostic heterogeneity in this population and has the potential to advance individualized treatment strategies.

Keywords:

blood biomarker; chronic stress; comorbid anxiety; genetic animal model; major depression

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