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Hunting for Peripheral Biomarkers to Support Drug Development in Psychiatry

  • Enrico Domenici
  • Pierandrea Muglia
  • Emilio Merlo-Pich
Chapter

Abstract

The development of novel treatments in psychiatry is suffering from the lack of objective criteria to select patients on the basis of measurable diagnostic parameters and biological markers to predict drug response. Clinical trials are usually long-term investigations, involving a large number of patients across multiple sites in the attempt to obtain sufficient statistical power, where drug efficacy is assessed by rather subjective and poorly sensitive psychopathologic rating scales. There is a clear need for hard read-outs that could complement the clinician’s assessment at different stages of the trial, creating the premises for more effective “proof of concept” studies. Biological or molecular markers have long been investigated in psychiatry mainly on the basis of mechanistic hypotheses. Although the results are encouraging, there is substantial lack of replication for most putative biomarkers investigated so far. Owing to the heterogeneity of psychiatric disorders, it appears unlikely that markers based on single mechanisms might prove to be useful in the clinics, and approaches aimed at detecting biomarker profiles rather than single markers are warranted. The search for peripheral biomarkers is supported by the evidence of multiple interactions between the brain and the periphery through complex neuroendocrine and neuroinflammatory networks. Recent developments in the application of genomic, proteomic, and metabonomic approaches are creating novel opportunities for the search of multiple biomarkers in psychiatry, opening up the chance to explore novel pathways in an unbiased manner. A series of studies documenting the possibility of detecting molecular signatures for psychiatric diseases and drug response in blood by large-scale approaches are reported. Integration of biomarker profiling approaches with neuroimaging strategies and genetic approaches on a genomewide scale is expected to increase the chance of identifying novel markers which could assist modern drug development in psychiatry.

Keywords

Major Depressive Disorder Peripheral Marker Peripheral BDNF Central Nervous System Level Food Drug Administration 
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

BDNF

Brain-derived neurotrophic factor

CNS

Central nervous system

CRH

Corticotropin releasing hormone

CSF

Cerebrospinal fluid

FDA

Food and Drug Administration

HAM-D

Hamilton rating scale for depression

HPA

Hypothalamus–pituitary–adrenocortical

MRI

Magnetic resonance imaging

PBMC

Peripheral blood mononuclear cell

PoC

Proof of concept

PTSD

Post-traumatic stress disorder

Notes

Acknowledgments

The authors thank the members of the psychiatry biomarker team at GSK for their valuable support.

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Enrico Domenici
    • 1
  • Pierandrea Muglia
    • 1
  • Emilio Merlo-Pich
    • 1
  1. 1.Biology, Psychiatry CEDDGlaxoSmithKline Medicines Research CentreVeronaItaly

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