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Association of the enkephalinase gene with low amplitude P300 waves

D E Comings1, G Dietz, J P Johnson

  • 1Department of Medical Genetics, City of Hope Medical Center, Duarte, CA 91010, USA.

Neuroreport
|August 10, 1999
PubMed

Insights

Low P300 evoked potential wave amplitude in substance abuse may be linked to the MME gene. Specific MME gene variants (low mol. wt alleles) were associated with reduced P300 amplitude, suggesting endogenous opioid involvement.

Area of Science:

  • Neuroscience
  • Genetics
  • Psychiatry

Background:

  • Low amplitude of P300 evoked potential waves is associated with substance abuse.
  • Opioidergic gene defects are implicated as risk factors for substance abuse.
  • Enkephalin degradation rate influences central nervous system (CNS) enkephalin levels.

Purpose of the Study:

  • To investigate the association between a MME gene polymorphism and P300 wave amplitude in individuals with substance abuse.
  • To explore the role of endogenous opioids in regulating P300 wave amplitude.

Main Methods:

  • Identified a GT repeat polymorphism 5' to the metallo-membrane endopeptidase (MME) gene.
  • Examined the association between this polymorphism and P300 wave amplitude in 25 male subjects with substance abuse.
  • Analyzed P300 wave amplitude at parietal and coronal leads.

Main Results:

  • A significant association was found between low molecular weight (mol. wt) alleles of the MME gene and low amplitude of the P300 wave.
  • This association was significant at both parietal (p = 0.0087) and coronal (p = 0.009) leads.
  • The findings suggest a link between MME gene variants and P300 amplitude regulation.

Conclusions:

  • The study supports a role for endogenous opioids in the regulation of P300 wave amplitude.
  • Genetic variations in the MME gene may influence susceptibility to substance abuse through modulation of reward pathways.
  • Further research is warranted to elucidate the precise mechanisms linking MME genotype, opioid signaling, and neurophysiological markers in substance abuse.

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