Title - Feature Finding
Featured Finding Figure
In the prefrontal cortex (PFC) of subjects with schizophrenia, decreased signaling mediated by brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, appears to contribute to the reduced expression of mRNA encoding the 67-kilodalton isoform of glutamate decarboxylase (GAD67), an enzyme for GABA synthesis. We tested the effect of a single nucleotide polymorphism (Val66Met) in the human BDNF gene, which reduces the trafficking and secretion of BDNF protein, on the expression of GAD67 mRNA in schizophrenia. BDNF Val66Met genotype was determined in 27 matched pairs of schizophrenia and control subjects. The impact of this polymorphism on PFC GAD67 mRNA expression in schizophrenia subjects was assessed by comparing within-subject-pair differences in GAD67 mRNA expression between schizophrenia subjects with or without the Met66 allele, while controlling for the level of BDNF mRNA expression. Panel A of the figure shows BDNF Val66Met genotype of the control and schizophrenia subjects in each pair and the percentage changes in BDNF and GAD67 mRNA expression in the schizophrenia subjects relative to their matched control subjects. Panel B shows the mean (SD) percentage changes in BDNF and GAD67 mRNA expression in 20 subject pairs without the Met66 allele and in 5 pairs with the Met66 allele only in the schizophrenia subjects. In contrast to expectations, the presence of non-intersecting lines connecting the mean percentage changes in the BDNF and GAD67 mRNAs indicates the absence of an effect of bdnf genotype on GAD67 mRNA expression after controlling for the level of BDNF mRNA expression (F1,23 = 0.22, P = 0.88). These findings indicate that the presence of the BDNF Met66 allele does not contribute to the decreased level of GAD67 mRNA expression in the PFC of subjects with schizophrenia.
Hashimoto T, Lewis DA: BDNF Val66Met Polymorphism and GAD67 mRNA expression in the prefrontal cortex of subjects with schizophrenia. Am J Psychiatry 163: 534-537, 2006.

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David A. Lewis, M.D. | Department of Psychiatry | University of Pittsburgh
3811 O'Hara Street, Biomedical Science Tower W1654
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