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

• Published in: Neuroreport Vol. 18; no. 1; p. 57
• Main Authors: Guidotti, Alessandro, Ruzicka, William, Grayson, Dennis R, Veldic, Marin, Pinna, Graziano, Davis, John M, Costa, Erminio
• Format: Journal Article
• Language: English
• Published: England 08.01.2007
• Subjects: Cell Adhesion Molecules, Neuronal - genetics; Cell Adhesion Molecules, Neuronal - metabolism; Chromatography, High Pressure Liquid - methods; Cohort Studies; DNA (Cytosine-5-)-Methyltransferase 1; DNA (Cytosine-5-)-Methyltransferases - genetics; DNA (Cytosine-5-)-Methyltransferases - metabolism; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; Gene Expression Regulation - physiology; Glutamate Decarboxylase - genetics; Glutamate Decarboxylase - metabolism; Humans; Isoenzymes - genetics; Isoenzymes - metabolism; Mental Disorders - pathology; Mental Disorders - physiopathology; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Prefrontal Cortex - metabolism; RNA, Messenger - metabolism; S-Adenosylmethionine - metabolism; Serine Endopeptidases - genetics; Serine Endopeptidases - metabolism
• DOI: 10.1097/WNR.0b013e32800fefd7
• ISSN: 0959-4965

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.