BDNF Val66Met polymorphism and GAD67 mRNA expression in the prefrontal cortex of subjects with schizophrenia.
OBJECTIVE
In the prefrontal cortex of subjects with schizophrenia, decreased signaling mediated by brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase (TrkB) appears to contribute to the reduced expression of mRNA encoding the 67-kilodalton isoform of glutamate decarboxylase (GAD(67)), an enzyme for GABA synthesis. The authors examined in subjects with schizophrenia the effect in the human BDNF gene of a single nucleotide polymorphism (Val66Met), which reduces the trafficking and secretion of BDNF protein, on the expression of GAD(67) mRNA.


METHODS
BDNF Val66Met genotyping was performed in 27 matched pairs of schizophrenia and comparison subjects. The impact of this polymorphism on prefrontal cortex GAD(67) mRNA expression in schizophrenia subjects was assessed by comparing within-pair differences in GAD(67) mRNA expression between schizophrenia subjects with versus without the Met66 allele after the level of BDNF mRNA expression was controlled.


RESULTS
In contrast to expectations, the within-pair reduction in GAD(67) mRNA expression was not greater in schizophrenia subjects who were hetero- or homozygous for the Met66 allele. These subjects did tend to exhibit less marked within-pair reductions in both GAD(67) and BDNF mRNA expression compared with schizophrenia subjects homozygous for the Val allele.


CONCLUSIONS
The presence of the BDNF Met66 allele does not contribute to the decreased level of GAD(67) mRNA expression in the prefrontal cortex of subjects with schizophrenia.
Hashimoto
Takanori
T
Department of Psychiatry, University of Pittsburgh, PA 15213, USA.
Lewis
David A
DA
D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D003975:Diazepam / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008715:Methionine; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis
D019208:Brain-Derived Neurotrophic Factor; D007527:Isoenzymes; D012333:RNA, Messenger; D005680:gamma-Aminobutyric Acid; D008715:Methionine; D020813:Receptor, trkB; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D003975:Diazepam