title: Elevated glutamatergic compounds in pregenual anterior cingulate in pediatric autism spectrum disorder demonstrated by 1H MRS and 1H MRSI.
abstract: Recent research in autism spectrum disorder (ASD) has aroused interest in anterior cingulate cortex and in the neurometabolite glutamate. We report two studies of pregenual anterior cingulate cortex (pACC) in pediatric ASD. First, we acquired in vivo single-voxel proton magnetic resonance spectroscopy ((1)H MRS) in 8 children with ASD and 10 typically developing controls who were well matched for age, but with fewer males and higher IQ. In the ASD group in midline pACC, we found mean 17.7% elevation of glutamate + glutamine (Glx) (p<0.05) and 21.2% (p<0.001) decrement in creatine + phosphocreatine (Cr). We then performed a larger (26 subjects with ASD, 16 controls) follow-up study in samples now matched for age, gender, and IQ using proton magnetic resonance spectroscopic imaging ((1)H MRSI). Higher spatial resolution enabled bilateral pACC acquisition. Significant effects were restricted to right pACC where Glx (9.5%, p<0.05), Cr (6.7%, p<0.05), and N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (10.2%, p<0.01) in the ASD sample were elevated above control. These two independent studies suggest hyperglutamatergia and other neurometabolic abnormalities in pACC in ASD, with possible right-lateralization. The hyperglutamatergic state may reflect an imbalance of excitation over inhibition in the brain as proposed in recent neurodevelopmental models of ASD.
authors: Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.
authors: Anthony
authors: A
authors: Bejjani
authors: Joseph
authors: J
authors: O'Neill
authors: John A
authors: JA
authors: Kim
authors: Andrew J
authors: AJ
authors: Frew
authors: Victor W
authors: VW
authors: Yee
authors: Ronald
authors: R
authors: Ly
authors: Christina
authors: C
authors: Kitchen
authors: Noriko
authors: N
authors: Salamon
authors: James T
authors: JT
authors: McCracken
authors: Arthur W
authors: AW
authors: Toga
authors: Jeffry R
authors: JR
authors: Alger
authors: Jennifer G
authors: JG
authors: Levitt
mesh_terms: D000293:Adolescent; D001923:Brain Chemistry; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008959:Models, Neurological; D010725:Phosphocreatine / Q000378:metabolism*; D010865:Pilot Projects; D011859:Radiography
chemical_list: D010725:Phosphocreatine; D005973:Glutamine; D018698:Glutamic Acid