Methylation and D4 Dopamine Receptors in Autism and Schizophrenia

Nova Southeastern University, Davie, Florida, USA

Objective. To evaluate the role of methylation in regulating the D4 dopamine receptor in autism and schizophrenia Background. D4 dopamine receptors have the unique ability to catalyze methylation of membrane phospholipids, involving the vitamin B12 and folate-dependent enzyme methionine synthase. This process is proposed to be centrally involved in dopamine-mediated attention by synchronization of neural network activity. Impaired methylation has been reported in autism and schizophrenia. Methods. Levels of vitamin B12 (cobalamin) in postmortem brain samples were analyzed by HPLC. DNA methylation of CpG sites in intron 1 of the D4 receptor were measured by pyrosequencing and global DNA methylation was measured via an Elisa-based assay. Results. Vitamin B12 levels, especially methylcobalamin, were decreased in both autism and schizophrenia frontal cortex. Methylation of the D4 dopamine receptor was significantly higher in both autism and schizophrenia. Conclusion. Methylation status of the D4 dopamine receptor gene is abnormal in autism and schizophrenia, associated with lower levels of vitamin B12. Grants. This study was funded in part by the Autism Research Institute.