title: Fronto-Striatal Glutamate in Autism Spectrum Disorder and Obsessive Compulsive Disorder.
abstract: Autism spectrum disorders (ASDs) and obsessive compulsive disorder (OCD) are often comorbid with the overlap based on compulsive behaviors. Although previous studies suggest glutamatergic deficits in fronto-striatal brain areas in both disorders, this is the first study to directly compare the glutamate concentrations across the two disorders with those in healthy control participants using both categorical and dimensional approaches. In the current multi-center study (four centers), we used proton magnetic resonance spectroscopy in 51 children with ASD, 29 with OCD, and 53 healthy controls (aged 8-13 years) to investigate glutamate (Glu) concentrations in two regions of the fronto-striatal circuit: midline anterior cingulate cortex (ACC) and left dorsal striatum. Spectra were processed with Linear Combination Model. Group comparisons were performed with one-way analyses of variance including sex, medication use, and scanner site as covariates. In addition, a dimensional analysis was performed, linking glutamate with a continuous measure of compulsivity across disorders. There was a main group effect for ACC glutamate (p=0.019). Contrast analyses showed increased glutamate both in children with ASD and OCD compared with controls (p=0.007), but no differences between the two disorders (p=0.770). Dimensional analyses revealed a positive correlation between compulsive behavior (measured with the Repetitive Behavior Scale) and ACC glutamate (rho=0.24, p=0.03). These findings were robust across sites. No differences were found in the striatum. The current findings confirm overlap between ASD and OCD in terms of glutamate involvement. Glutamate concentration in ACC seems to be associated with the severity of compulsive behavior.
authors.affiliation: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jilly
authors.initials: J
authors.lastname: Naaijen
authors.affiliation: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Marcel P
authors.initials: MP
authors.lastname: Zwiers
authors.affiliation: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.|Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Houshang
authors.initials: H
authors.lastname: Amiri
authors.affiliation: Department of Neuroimaging, King's College London, Institute of Psychiatry, Psychology, and Neuroscience, London, UK.
authors.forename: Steven C R
authors.initials: SCR
authors.lastname: Williams
authors.affiliation: NICHE Lab, Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Sarah
authors.initials: S
authors.lastname: Durston
authors.affiliation: NICHE Lab, Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Bob
authors.initials: B
authors.lastname: Oranje
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty, Heidelberg University, Mannheim, Germany.|Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Zurich, Switzerland.|Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.|Neuroscience Center Zurich, University of Zurich, ETH Zurich, Zurich, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Brandeis
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty, Heidelberg University, Mannheim, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Boecker-Schlier
authors.affiliation: Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty, Heidelberg University, Mannheim, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Ruf
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty, Heidelberg University, Mannheim, Germany.|Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty, Heidelberg University, Mannheim, Germany.
authors.forename: Isabella
authors.initials: I
authors.lastname: Wolf
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty, Heidelberg University, Mannheim, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
authors.affiliation: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Glennon
authors.affiliation: Department of Human Genetics, Donders Institute of Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.|Department of Psychiatry, Donders Institute of Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Barbara
authors.identifier: http://orcid.org/0000-0003-4375-6572
authors.initials: B
authors.lastname: Franke
authors.affiliation: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.|Karakter Child and Adolescent Psychiatry University Center, Nijmegen, The Netherlands.
authors.forename: Jan K
authors.initials: JK
authors.lastname: Buitelaar
authors.affiliation: Department of Neuroimaging, King's College London, Institute of Psychiatry, Psychology, and Neuroscience, London, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lythgoe
mesh_terms: D000293:Adolescent; D000067877:Autism Spectrum Disorder / Q000175:diagnosis / Q000378:metabolism*; D002648:Child; D003342:Corpus Striatum / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis / Q000378:metabolism*
chemical_list: D018698:Glutamic Acid