S-adenosyl methionine and DNA methyltransferase-1 mRNA overexpression in psychosis.
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.
Guidotti
Alessandro
A
Department of Psychiatry, Psychiatric Institute, University of Illinois, Chicago, Illinois, USA.
Ruzicka
William
W
Grayson
Dennis R
DR
Veldic
Marin
M
Pinna
Graziano
G
Davis
John M
JM
Costa
Erminio
E
D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D015331:Cohort Studies; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D001523:Mental Disorders / Q000473:pathology / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000091042:Reelin Protein; D012436:S-Adenosylmethionine / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000091042:Reelin Protein; D012436:S-Adenosylmethionine; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000717127:RELN protein, human; D012697:Serine Endopeptidases; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1