title: Disturbed cingulate glutamate metabolism in adults with high-functioning autism spectrum disorder: evidence in support of the excitatory/inhibitory imbalance hypothesis.
abstract: Over the last few years, awareness of autism spectrum disorder (ASD) in adults has increased. The precise etiology of ASD is still unresolved. Animal research, genetic and postmortem studies suggest that the glutamate (Glu) system has an important role, possibly related to a cybernetic imbalance between neuronal excitation and inhibition. To clarify the possible disruption of Glu metabolism in adults with high-functioning autism, we performed a magnetic resonance spectroscopy (MRS) study investigating the anterior cingulate cortex (ACC) and the cerebellum in adults with high-functioning ASD. Twenty-nine adult patients with high-functioning ASD and 29 carefully matched healthy volunteers underwent MRS scanning of the pregenual ACC and the left cerebellar hemisphere. Metabolic data were compared between groups and were correlated with psychometric measures of autistic features. We found a significant decrease in the cingulate N-acetyl-aspartate (NAA) and the combined Glu and glutamine (Glx) signals in adults with ASD, whereas we did not find other metabolic abnormalities in the ACC or the cerebellum. The Glx signal correlated significantly with psychometric measures of autism, particularly with communication deficits. Our data support the hypothesis that there is a link between disturbances of the cingulate NAA and Glx metabolism, and autism. The findings are discussed in the context of the hypothesis of excitatory/inhibitory imbalance in autism. Further research should clarify the specificity and dynamics of these findings regarding other neuropsychiatric disorders and other brain areas.
authors.affiliation: 1] Section for Experimental Neuropsychiatry, Department for Psychiatry and Psychotherapy, Albert-Ludwigs-University, Freiburg, Germany [2] Universitäres Zentrum Autismus Spektrum, Albert-Ludwigs-University, Freiburg, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Tebartz van Elst
authors.affiliation: Section for Experimental Neuropsychiatry, Department for Psychiatry and Psychotherapy, Albert-Ludwigs-University, Freiburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Maier
authors.affiliation: 1] Section for Experimental Neuropsychiatry, Department for Psychiatry and Psychotherapy, Albert-Ludwigs-University, Freiburg, Germany [2] Universitäres Zentrum Autismus Spektrum, Albert-Ludwigs-University, Freiburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Fangmeier
authors.affiliation: Section for Experimental Neuropsychiatry, Department for Psychiatry and Psychotherapy, Albert-Ludwigs-University, Freiburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Endres
authors.affiliation: Section for Experimental Neuropsychiatry, Department for Psychiatry and Psychotherapy, Albert-Ludwigs-University, Freiburg, Germany.
authors.forename: G T
authors.initials: GT
authors.lastname: Mueller
authors.affiliation: Section for Experimental Neuropsychiatry, Department for Psychiatry and Psychotherapy, Albert-Ludwigs-University, Freiburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Nickel
authors.affiliation: 1] Section for Experimental Neuropsychiatry, Department for Psychiatry and Psychotherapy, Albert-Ludwigs-University, Freiburg, Germany [2] Universitäres Zentrum Autismus Spektrum, Albert-Ludwigs-University, Freiburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Ebert
authors.affiliation: 1] Department for Radiology, Medical Physics, University Medical Center Freiburg, Freiburg, Germany [2] Freiburg Institute for Advanced Studies (FRIAS), Albert-Ludwigs-University, Freiburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Lange
authors.affiliation: Department for Radiology, Medical Physics, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Hennig
authors.affiliation: 1] Section for Experimental Neuropsychiatry, Department for Psychiatry and Psychotherapy, Albert-Ludwigs-University, Freiburg, Germany [2] Universitäres Zentrum Autismus Spektrum, Albert-Ludwigs-University, Freiburg, Germany [3] Department for Child & Adolescent Psychiatry & Psychotherapy, Albert-Ludwigs-University, Freiburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Biscaldi
authors.affiliation: Universitäres Zentrum Autismus Spektrum, Albert-Ludwigs-University, Freiburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Riedel
authors.affiliation: Section for Experimental Neuropsychiatry, Department for Psychiatry and Psychotherapy, Albert-Ludwigs-University, Freiburg, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Perlov
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001931:Brain Mapping; D002531:Cerebellum / Q000378:metabolism; D002659:Child Development Disorders, Pervasive / Q000378:metabolism* / Q000523:psychology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D006179:Gyrus Cinguli / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011594:Psychometrics
chemical_list: D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate