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Imaging neurochemical endophenotypes: promises and pitfalls.

D Martinez1, A Broft, M Laruelle

  • 1New York State Psychiatric Institute, 1051 Riverside Drive, Box #31, New York, NY 10032, USA. dm437@columbia.edu

Pharmacogenomics
|September 6, 2001
PubMed
Summary

Genetic variations in neurotransmitter genes are linked to neuropsychiatric disorders. Brain imaging studies using SPECT and PET help clarify the functional significance of these genetic polymorphisms for drug development.

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Area of Science:

  • Neuroscience
  • Psychiatric Genetics
  • Pharmacology

Background:

  • Polymorphisms in neurotransmitter receptor and transporter genes are frequently associated with neuropsychiatric conditions.
  • However, consistent replication of these genetic associations remains a challenge.
  • These proteins are key targets for psychoactive medications, making their genetic variations relevant for drug development.

Purpose of the Study:

  • To review brain imaging studies that evaluate the significance of polymorphisms in genes encoding critical drug targets.
  • To explore the expression and function of these targets in the living human brain using imaging techniques.
  • To highlight the opportunities and challenges of integrating genetic analysis with brain imaging.

Main Methods:

  • Review of brain imaging studies (SPECT, PET) investigating gene polymorphisms.

Related Experiment Videos

  • Focus on polymorphisms in genes for serotonin transporter (SERT), dopamine transporter (DAT), and dopamine D(2) receptor.
  • Correlation of genetic variations with in vivo protein expression and function.

    • Main Results:

    • Brain imaging provides a method to assess the functional impact of genetic variations in vivo.
    • Studies demonstrate varying degrees of success in linking specific polymorphisms to altered transporter or receptor expression/function.
    • The combination of genetic and imaging data offers insights into individual differences in drug response.

    Conclusions:

    • Brain imaging techniques like SPECT and PET are valuable tools for understanding the functional relevance of gene polymorphisms in neuropsychiatric disorders.
    • This approach can guide personalized medicine and the development of novel therapeutics targeting neurotransmitter systems.
    • Further research is needed to overcome methodological challenges and fully leverage the potential of combined genetic and imaging analyses.