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


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.


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.



Serine/threonine-specific protein kinase


Analysis of Variance


B-cell leukemia/lymphoma 2


Brain derived neurotrophic factor


Chronic mild stress


Corticotropin-releasing factor


Disrupted-in-schizophrenia 1


Deoxyribonucleic acid


Diagnostic and Statistical Manual


Dexamethasone suppression test


Forced swim test


Glucocorticoid receptor


rats High anxiety bred rats


axis Hypothalamic–pituitary–adrenal axis




Human Proteome Organization


International Classification of Diseases


rats Low anxiety bred rats


Locus coeruleus


Learned helplessness


Metabotropic glutamate 2/3 receptor


Medial prefrontal cortex


Mineralocorticoid receptor


New Chemical Entity


National Institute of Mental Health




Peripheral blood mononuclear cells


Penalized logistic regression


Proteomics Data Collection


Quantitative Polymerase-chain reaction


Ribonucleic acid


Subgranular zone


Small interfering ribonucleic acid


Stepwise logistic regression


Subventricular zone


Tail suspension test


Vascular endothelial growth factor



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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