TY - JOUR T1 - Genetic Association of ErbB4 and Human Cortical GABA Levels <em>In Vivo</em> JF - The Journal of Neuroscience JO - J. Neurosci. SP - 11628 LP - 11632 DO - 10.1523/JNEUROSCI.1529-11.2011 VL - 31 IS - 32 AU - Stefano Marenco AU - Matthew Geramita AU - Jan Willem van der Veen AU - Alan S. Barnett AU - Bhaskar Kolachana AU - Jun Shen AU - Daniel R. Weinberger AU - Amanda J. Law Y1 - 2011/08/10 UR - http://www.jneurosci.org/content/31/32/11628.abstract N2 - NRG1-ErbB4 signaling controls inhibitory circuit development in the mammalian cortex through ErbB4-dependent regulation of GABAergic interneuron connectivity. Common genetic variation in ErbB4 (rs7598440) has been associated with ErbB4 messenger RNA levels in the human cortex and risk for schizophrenia. Recent work demonstrates that Erbb4 is expressed exclusively on inhibitory interneurons, where its presence on parvalbumin-positive cells mediates the effects of NRG1 on inhibitory circuit formation in the cortex. We therefore hypothesized that genetic variation in ErbB4 at rs7598440 would impact indices of GABA concentration in the human cortex. We tested this hypothesis in 116 healthy volunteers by measuring GABA and GLX (glutamate + glutamine) with proton magnetic resonance spectroscopy in the dorsal anterior cingulate gyrus. ErbB4 rs7598440 genotype significantly predicted cortical GABA concentration (p = 0.014), but not GLX (p = 0.51), with A allele carriers having higher GABA as predicted by the allelic impact on ErbB4 expression. These data establish an association of ErbB4 and GABA in human brain and have implications for understanding the pathogenesis of schizophrenia and other psychiatric disorders. ER -