TY - JOUR
T1 - Genetic association of ErbB4 and human cortical GABA levels in vivo
AU - Marenco, Stefano
AU - Geramita, Matthew
AU - van der Veen, Jan Willem
AU - Barnett, Alan S.
AU - Kolachana, Bhaskar
AU - Shen, Jun
AU - Weinberger, Daniel R.
AU - Law, Amanda J.
PY - 2011/8/10
Y1 - 2011/8/10
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 ofNRG1on 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.Wetested 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.
AB - 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 ofNRG1on 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.Wetested 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.
UR - http://www.scopus.com/inward/record.url?scp=80051567966&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80051567966&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.1529-11.2011
DO - 10.1523/JNEUROSCI.1529-11.2011
M3 - Article
C2 - 21832192
AN - SCOPUS:80051567966
SN - 0270-6474
VL - 31
SP - 11628
EP - 11632
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 32
ER -