Prefrontal GABAA receptor α-subunit expression in normal postnatal human development and schizophrenia

Cortical GABA deficits that are consistently reported in schizophrenia may reflect an etiology of failed normal postnatal neurotransmitter maturation. Previous studies have found prefrontal cortical GABA(A) receptor alpha subunit alterations in schizophrenia, yet their relationship to normal developmental expression profiles in the human cortex has not been determined. The aim of this study was to quantify GABAA receptor alpha-subunit mRNA expression patterns in human dorsolateral prefrontal cortex (DLPFC) during normal postnatal development and in schizophrenia cases compared to controls. Transcript levels of GABAA receptor alpha subunits were measured using microarray and qPCR analysis of 60 normal individuals aged 6 weeks to 49 years and in 37 patients with schizophrenia/schizoaffective disorder and 37 matched controls. We detected robust opposing changes in cortical GABAA receptor alpha 1 and as subunits during the first few years of postnatal development, with a 60% decrease in alpha 5 mRNA expression and a doubling of alpha 1 mRNA expression with increasing age. In our Australian schizophrenia cohort we detected decreased GAD67 mRNA expression (p = 0.0012) and decreased alpha 5 mRNA expression (p = 0.038) in the DLPFC with no significant change of other a subunits. Our findings confirm that GABA deficits (reduced GAD67) are a consistent feature of schizophrenia postmortem brain studies. Our study does not confirm alterations in cortical alpha 1 or alpha 2 mRNA levels in the schizophrenic DLPFC, as seen in previous studies, but instead we report a novel down-regulation of alpha 5 subunit mRNA suggesting that post-synaptic alterations of inhibitory receptors are an important feature of schizophrenia but may vary between cohorts. (C) 2009 Elsevier Ltd. All rights reserved.