title: Glutamate/glutamine and neuronal integrity in adults with ADHD: a proton MRS study.
abstract: There is increasing evidence that abnormalities in glutamate signalling may contribute to the pathophysiology of attention-deficit hyperactivity disorder (ADHD). Proton magnetic resonance spectroscopy ([1H]MRS) can be used to measure glutamate, and also its metabolite glutamine, in vivo. However, few studies have investigated glutamate in the brain of adults with ADHD naive to stimulant medication. Therefore, we used [1H]MRS to measure the combined signal of glutamate and glutamine (Glu+Gln; abbreviated as Glx) along with other neurometabolites such as creatine (Cr), N-acetylaspartate (NAA) and choline. Data were acquired from three brain regions, including two implicated in ADHD-the basal ganglia (caudate/striatum) and the dorsolateral prefrontal cortex (DLPFC)-and one 'control' region-the medial parietal cortex. We compared 40 adults with ADHD, of whom 24 were naive for ADHD medication, whereas 16 were currently on stimulants, against 20 age, sex and IQ-matched healthy controls. We found that compared with controls, adult ADHD participants had a significantly lower concentration of Glx, Cr and NAA in the basal ganglia and Cr in the DLPFC, after correction for multiple comparisons. There were no differences between stimulant-treated and treatment-naive ADHD participants. In people with untreated ADHD, lower basal ganglia Glx was significantly associated with more severe symptoms of inattention. There were no significant differences in the parietal 'control' region. We suggest that subcortical glutamate and glutamine have a modulatory role in ADHD adults; and that differences in glutamate-glutamine levels are not explained by use of stimulant medication.
authors.affiliation: 1] Adult ADHD Service, The Maudsley Hospital, London, UK [2] King's College London, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Maltezos
authors.affiliation: King's College London, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Horder
authors.affiliation: King's College London, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Coghlan
authors.affiliation: King's College London, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Skirrow
authors.affiliation: King's College London, Department of Neuroimaging, Institute of Psychiatry, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: O'Gorman
authors.affiliation: King's College London, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, London, UK.
authors.forename: T J
authors.initials: TJ
authors.lastname: Lavender
authors.affiliation: 1] King's College London, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, London, UK [2] Autism Assessment and Behavioural Genetics Clinic, South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital, Beckenham, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Mendez
authors.affiliation: King's College London, Department of Neuroimaging, Institute of Psychiatry, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Mehta
authors.affiliation: King's College London, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, London, UK.
authors.forename: E
authors.initials: E
authors.lastname: Daly
authors.affiliation: 1] Adult ADHD Service, The Maudsley Hospital, London, UK [2] King's College London, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, London, UK.
authors.forename: K
authors.initials: K
authors.lastname: Xenitidis
authors.affiliation: Adult ADHD Service, The Maudsley Hospital, London, UK.
authors.forename: E
authors.initials: E
authors.lastname: Paliokosta
authors.affiliation: 1] King's College London, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, London, UK [2] Autism Assessment and Behavioural Genetics Clinic, South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital, Beckenham, UK.
authors.forename: D
authors.initials: D
authors.lastname: Spain
authors.affiliation: Adult ADHD Service, The Maudsley Hospital, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Pitts
authors.affiliation: 1] Adult ADHD Service, The Maudsley Hospital, London, UK [2] King's College London, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Asherson
authors.affiliation: King's College London, Department of Neuroimaging, Institute of Psychiatry, London, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Lythgoe
authors.affiliation: King's College London, Department of Neuroimaging, Institute of Psychiatry, London, UK.
authors.forename: G J
authors.identifier: 0000000252147421
authors.initials: GJ
authors.lastname: Barker
authors.affiliation: 1] King's College London, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, London, UK [2] Autism Assessment and Behavioural Genetics Clinic, South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital, Beckenham, UK [3] Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, King's College London, London, UK.
authors.forename: D G
authors.initials: DG
authors.lastname: Murphy
mesh_terms: D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000378:metabolism*; D001479:Basal Ganglia / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D017397:Prefrontal Cortex / Q000378:metabolism*
chemical_list: D005973:Glutamine; D018698:Glutamic Acid