Increased DNA methylation in the parvalbumin gene promoter is associated with methamphetamine dependence

Pharmacogenomics. 2017 Sep;18(14):1317-1322. doi: 10.2217/pgs-2016-0188. Epub 2017 Aug 24.

Abstract

Aim: The parvalbumin (PV)-containing subgroup of GABAergic neurons is particularly affected in schizophrenia and animal models of psychosis, including after methamphetamine (METH) administration. We investigated whether METH dependence and METH-induced psychosis may involve an effect on DNA methylation of the PVALB promoter.

Materials & methods: The methylation of a PVALB promoter sequence was determined in 100 METH-dependent and 102 control subjects using pyrosequencing.

Results: A significant increase in PVALB methylation was observed in METH dependence and METH-induced psychosis. No significant effect on long interspersed nucleotide element-1 methylation, a measure of global DNA methylation, was observed.

Conclusion: These results demonstrate a specific association between elevated PVALB methylation and METH-induced psychosis. This finding may contribute to the GABAergic deficits associated with METH dependence.

Keywords: DNA methylation; methamphetamine dependence; parvalbumin.

MeSH terms

  • Adult
  • Amphetamine-Related Disorders / genetics*
  • DNA Methylation*
  • Humans
  • Male
  • Methamphetamine / toxicity*
  • Parvalbumins / genetics*
  • Promoter Regions, Genetic*
  • Psychoses, Substance-Induced / genetics*

Substances

  • Parvalbumins
  • Methamphetamine