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 (GAD₆₇), 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 GAD₆₇ mRNA. METHOD: BDNF Val66Met genotyping was performed in 27 matched pairs of schizophrenia and comparison subjects. The impact of this polymorphism on prefrontal cortex GAD₆₇ mRNA expression in schizophrenia subjects was assessed by comparing within-pair differences in GAD₆₇ 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 GAD₆₇ 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 GAD₆₇ 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 GAD₆₇ mRNA expression in the prefrontal cortex of subjects with schizophrenia.