S-adenosyl methionine and DNA methyltransferase-1 mRNA... : NeuroReport (original) (raw)

NEUROCHEMISTRY

_S_-adenosyl methionine and DNA methyltransferase-1 mRNA overexpression in psychosis

Guidotti, Alessandro; Ruzicka, William; Grayson, Dennis R.; Veldic, Marin; Pinna, Graziano; Davis, John M.; Costa, Erminio

Department of Psychiatry, Psychiatric Institute, University of Illinois, Chicago, Illinois, USA

Correspondence and requests for reprints to Erminio Costa, MD, Director of the Psychiatric Institute, University of Illinois at Chicago, 1601 Taylor, Chicago, IL 60612, USA

Tel: +1 312 413 4591; fax: +1 312 413 4569; e-mail: [email protected]

Sponsorship: This work is supported by RO1MH71667 to E.C., RO1MH6262A to D.R.G., and RO1MH70855 to A.G.

Received 15 August 2006; accepted 18 August 2006

Abstract

Prefrontal cortex (Brodmann's area 9) levels of the methyl donor _S_-adenosyl methionine were increased by about two-fold in schizophrenia and bipolar disorder patients, but not in unipolar depressed patients compared with nonpsychiatric subjects from the Stanley Foundation Neuropathology Consortium (Bethesda, Maryland, USA). Neither age, brain weight and pH, hemisphere, post-mortem interval, disease onset/duration, nor cumulative dose of fluphenazine affected _S_-adenosyl methionine content. In schizophrenia and bipolar disorder patients, the increase of _S_-adenosyl methionine is associated with an overexpression of DNA methyltransferase-1 mRNA in Brodmann's area 9 GABAergic neurons. Hence, the increased expression of _S_-adenosyl methionine and DNA methyltransferase-1 may contribute to promoter cytosine 5-methylation and to downregulation of the expression of mRNAs encoding for reelin and GAD67 in cortical GABAergic neurons of schizhophrenia and bipolar disorder patients.