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Perspectives for an Integrated Biomarker Approach to Drug Discovery and Development

  • Irina Antonijevic
  • Roman Artymyshyn
  • Carlos Forray
  • Sylvia Rabacchi
  • Kelli Smith
  • Chad Swanson
  • Joseph Tamm
  • Wiktor Mazin
  • Christophe Gerald
Chapter

Abstract

Today’s psychopharmacological drugs remain focused on targets that were identified serendipitously more than half a century ago. As these targets have not proven to be at the core of the pathophysiology of the major psychiatric disorders, a better understanding of the disease biology seems a crucial step to identify more efficacious treatments. The tools to realize this goal include neuroendocrine, protein, transcription and genetic markers, neuroimaging and neurophysiological approaches. Obviously, the benefit for psychiatric patients of identifying a pattern of blood-based markers that combine information on the disease biology and treatment response would be enormous. Our transcription data from human blood cells suggest that this is a realistic possibility for the future. Ideally, markers identified in patients would be translated into distinct, hypothesis-driven animal models to facilitate conclusions on the potential therapeutic utility of novel compounds. The combined use of disease state and mechanistic models may characterize cellular and molecular mechanisms of various aspects of psychiatric disorders. This information, in turn, could help establish in vitro models that link cellular targets to (novel) pharmacological approaches. With the discussions around DSM-V, it can be hoped that ambitious research agenda will guide and stimulate systematic research into the biology and biological markers of psychiatric disorders.

Keywords

Psychiatric Disorder Locus Coeruleus Force Swim Test Transcription Profile Tail Suspension Test 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

Akt

Serine/threonine-specific protein kinase

ANOVA

Analysis of Variance

Bcl-2

B-cell leukemia/lymphoma 2

BDNF

Brain derived neurotrophic factor

CMS

Chronic mild stress

CRF

Corticotropin-releasing factor

DISC-1

Disrupted-in-schizophrenia 1

DNA

Deoxyribonucleic acid

DSM

Diagnostic and Statistical Manual

DST

Dexamethasone suppression test

FST

Forced swim test

GR

Glucocorticoid receptor

HAB

rats High anxiety bred rats

HPA

axis Hypothalamic–pituitary–adrenal axis

5-HT

Serotonin

HUPO

Human Proteome Organization

ICD

International Classification of Diseases

LAB

rats Low anxiety bred rats

LC

Locus coeruleus

LH

Learned helplessness

mGlu2/3

Metabotropic glutamate 2/3 receptor

MPfc

Medial prefrontal cortex

MR

Mineralocorticoid receptor

NCE

New Chemical Entity

NIMH

National Institute of Mental Health

NRG1

Neuregulin-1

PBMC

Peripheral blood mononuclear cells

Pelora

Penalized logistic regression

ProDaC

Proteomics Data Collection

Qpcr

Quantitative Polymerase-chain reaction

RNA

Ribonucleic acid

SGZ

Subgranular zone

SiRNA

Small interfering ribonucleic acid

SLR

Stepwise logistic regression

SVZ

Subventricular zone

TST

Tail suspension test

VEGF

Vascular endothelial growth factor

Notes

Acknowledgments

The authors thank Erik Mosekilde from the Technical University of Denmark for his contribution to the exploratory statistical analyses of the transcription data generated by Lundbeck Research USA. The work done by Erik Mosekilde and Wiktor Mazin was supported by the European Union through the Network of Excellence BioSim, Contract No. LSHB-CT-2004-005137.

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Irina Antonijevic
    • 1
  • Roman Artymyshyn
    • 1
  • Carlos Forray
    • 1
  • Sylvia Rabacchi
    • 1
  • Kelli Smith
    • 1
  • Chad Swanson
    • 1
  • Joseph Tamm
    • 1
  • Wiktor Mazin
    • 1
  • Christophe Gerald
    • 1
  1. 1.Lundbeck Research USAParamusUSA

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