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

K Pajer,J Bridge,B M Andrus,A Lourie,K Dennis,G A Churchill,E E Redei,J Campo,K Blizinsky,P Vedell,B Strange,W Gardner

doi:10.1038/tp.2012.26

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.

Highlights

Early-onset major depressive disorder (MDD) is a serious psychiatric condition occurring in people under 25 years of age.[1]
There were 203 transcripts differentially expressed between WMI and WLI blood, and 167 transcripts (82.3%) had greater abundance in WLI as it is clearly visualized in the volcano plot (Figure 1a)
Our approach is innovative in combining theoretical and atheoretical strategies in animal models of depression to identify a panel of transcripts in the blood that did distinguish subjects with earlyonset MDD from those in the no disorder (ND) group

Summary

Introduction

Early-onset major depressive disorder (MDD) is a serious psychiatric condition occurring in people under 25 years of age.[1]. Treatments for early-onset MDD exist, but medication side effects are unpredictable and adolescents have lower response rates than adults.[13,14] Unmeasured heterogeneity in the etiology of MDD and the presence of symptom cluster subtypes that require unique treatments may explain these problems.[15,16] Current diagnostic practice is limited to patient self-report and clinician observation, methods that cannot adequately characterize this heterogeneity. Biological markers of different etiologic pathways and/or endophenotypes would provide objective data to augment verbal information and improve the accuracy of diagnosis. The diagnosis and classification of early-onset MDD could lead to a larger repertoire of more effective treatments and enhanced individualized care

Objectives

Methods

Results

Conclusion