Differential DNA modification of an enhancer at the IGF2 locus affects dopamine synthesis in patients with major psychosis

Abstract

Dopamine dysregulation is central to the pathogenesis of diseases with major psychosis, but its molecular origins are unclear. In an epigenome-wide investigation in neurons, individuals with schizophrenia and bipolar disorder showed reduced DNA modifications at an enhancer in IGF2, which disrupted the regulation of the dopamine synthesis enzyme tyrosine hydroxylase and striatal dopamine levels in transgenic mice. Epigenetic control of this enhancer may be an important molecular determinant of psychosis.