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

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 promoter. The methylation of a promoter sequence was determined in 100 METH-dependent and 102 control subjects using pyrosequencing. A significant increase in 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. These results demonstrate a specific association between elevated methylation and METH-induced psychosis. This finding may contribute to the GABAergic deficits associated with METH dependence.