Risk genes for schizophrenia: translational opportunities for drug discovery

Catherine L Winchester, Judith A Pratt, Brian J Morris

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Despite intensive research over many years, the treatment of schizophrenia remains a major health issue. Current and emerging treatments for schizophrenia are based upon the classical dopamine and glutamate hypotheses of disease. Existing first and second generation antipsychotic drugs based upon the dopamine hypothesis are limited by their inability to treat all symptom domains and their undesirable side effect profiles. Third generation drugs based upon the glutamate hypothesis of disease are currently under evaluation but are more likely to be used as add on treatments. Hence there is a large unmet clinical need. A major challenge in neuropsychiatric disease research is the relatively limited knowledge of disease mechanisms. However, as our understanding of the genetic causes of the disease evolves, novel strategies for the development of improved therapeutic agents will become apparent. In this review we consider the current status of knowledge of the genetic basis of schizophrenia, including methods for identifying genetic variants associated with the disorder and how they impact on gene function. Although the genetic architecture of schizophrenia is complex, some targets amenable to pharmacological intervention can be discerned. We conclude that many challenges lie ahead but the stratification of patients according to biobehavioural constructs that cross existing disease classifications but with common genetic and neurobiological bases, offer opportunities for new approaches to effective drug discovery.

Original languageEnglish
Pages (from-to)34-50
Number of pages17
JournalPharmacology and Therapeutics
Volume143
Issue number1
Early online date19 Feb 2014
DOIs
Publication statusPublished - Jul 2014

Fingerprint

Drug Discovery
Schizophrenia
Genes
Glutamic Acid
Dopamine
Inborn Genetic Diseases
Therapeutics
Research
Antipsychotic Agents
Pharmacology
Health
Pharmaceutical Preparations

Keywords

  • schizophrenia
  • genes
  • therapeutics
  • polymorphism
  • stratified medicines

Cite this

Winchester, Catherine L ; Pratt, Judith A ; Morris, Brian J. / Risk genes for schizophrenia : translational opportunities for drug discovery. In: Pharmacology and Therapeutics. 2014 ; Vol. 143, No. 1. pp. 34-50.
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Risk genes for schizophrenia : translational opportunities for drug discovery. / Winchester, Catherine L; Pratt, Judith A; Morris, Brian J.

In: Pharmacology and Therapeutics, Vol. 143, No. 1, 07.2014, p. 34-50.

Research output: Contribution to journalArticle

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