Changes of exon IV DNA methylation are associated with methamphetamine dependence.

We investigated DNA methylation of  in methamphetamine (METH) dependence in humans and an animal model. methylation at exon IV was determined by pyrosequencing of blood DNA from METH-dependent and control subjects, and from rat brain following an escalating dose of METH or vehicle. expression was determined in rat brain. methylation was increased in human METH dependence, greatest in subjects with psychosis and in prefrontal cortex of METH-administered rats; rat hippocampus showed reduced methylation and increased gene expression. methylation is abnormal in human METH dependence, especially METH-dependent psychosis, and in METH-administered rats. This may influence expression and contribute to the neurotoxic effects of METH exposure.